Kidneys

What research found here. What was shown to help comes first, then the risks reported, most common first.

Kidneys

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help40

Alpha-blockersStrongCommon

Passing a ureteral stone

Shown to raise stone passage, about 116 more per 1,000 in placebo-controlled trials, mainly for stones over 5 mm. Stones of 5 mm or less showed no clear benefit.

Compared with placebo or standard therapy [9]; placebo or control [10]

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Across all trials, stone clearance rose on an alpha-blocker (RR 1.45, 95% CI 1.36 to 1.55, low quality). In the higher-quality placebo-controlled trials the effect was smaller (RR 1.16, 95% CI 1.07 to 1.25), or 116 more clearances per 1,000. For stones 5 mm or smaller the RR was 1.06 (95% CI 0.98 to 1.15). Expulsion took 3.40 fewer days and hospital stays were fewer (RR 0.51) [9]. A second meta-analysis found more passage overall (RR 1.49, 95% CI 1.39 to 1.61), no clear benefit for smaller stones (RR 1.19, 95% CI 1.00 to 1.48) and 57% more passage for larger ones (RR 1.57, 95% CI 1.17 to 2.27), with less surgery (RR 0.44) [10].
Population: 10,509 adults in 67 trials, 5,787 of them in 15 placebo trials, with stones 1 cm or smaller [9]; 55 randomized trials [10].
Sources: [9], [10]
Caveats: Many trials were small and at risk of bias, and effects shrank in placebo-controlled trials [9]. Most trials used tamsulosin.

Cystatin CStrong

Estimating kidney function, cystatin C against creatinine

Shown to estimate measured kidney function about as closely as creatinine when used alone, and more closely when the two are combined.

The numbers and sources

Compared with: Measured glomerular filtration rate by clearance of an injected marker
Effect: In a validation set of 1,119 people, the share of estimates more than 30% away from measured GFR was 8.5% with the combined creatinine and cystatin C equation, 12.8% with the creatinine equation and 14.1% with the cystatin C equation. Bias was similar among the three, and the combined equation correctly reclassified 16.9% of people with a creatinine-based estimate of 45 to 59 mL/min/1.73 m2 as having a measured GFR of 60 or higher [4]. In 4,050 people, equations without a race term that combined creatinine and cystatin C were more accurate than the creatinine-only equations, with smaller differences between Black and non-Black participants [17]. A European equation using cystatin C, validated in 12,832 patients, was unbiased and similar in accuracy to the creatinine version, and the mean of the two was more accurate than either [18]. A kidney guideline states that the combined estimate is to be used when the creatinine-based one is less accurate and the result affects a clinical decision [2].
Population: 5,352 participants in 13 studies for development and 1,119 in 5 studies for validation [4]. 4,050 participants in 12 validation studies, 14.3% Black [17]. 11,231 patients from Europe, 1,093 from the United States and 508 from Africa [18].
Sources: [4], [17], [18], [2]
Caveats: These equations turn cystatin C into an estimated GFR in mL/min/1.73 m2, a different quantity from the mg/L result on this page, with its own categories. The guideline lists very high inflammation, high catabolic states and steroid use as sources of error in the combined estimate [2].

Cystatin CStrong

Death from any cause

Linked to more deaths at higher levels, and a cystatin C-based kidney estimate at least 30% below the creatinine-based one went with 69% more deaths.

The numbers and sources

Effect: In elderly US adults, hazard ratios for death rose across fifths of cystatin C, from 1.08 (95% CI 0.86 to 1.35) in the second fifth to 2.58 (2.03 to 3.27) in the top part of the highest fifth, while creatinine showed a J-shaped association [11]. In a meta-analysis of 16 cohorts, being reclassified to a lower kidney function category by cystatin C than by creatinine went with a higher risk of death, and to a higher category with a lower risk, with a net reclassification improvement for death of 0.23 (95% CI 0.18 to 0.28) [12]. In 440,526 UK adults, the cystatin C-based estimate of kidney function was the one most strongly associated with cardiovascular disease and death [13]. Across 23 outpatient cohorts, people whose cystatin C-based estimate was at least 30% lower than their creatinine-based one had 28.4 deaths per 1,000 person-years against 16.8 in those whose two estimates were within 30% (HR 1.69, 95% CI 1.57 to 1.82) [14].
Population: 4,637 participants of the Cardiovascular Health Study [11]. 90,750 participants in 11 general-population studies and 2,960 in 5 cohorts with chronic kidney disease, 13,202 deaths [12]. 440,526 UK Biobank participants [13]. 821,327 people in 23 outpatient cohorts, mean follow-up 11 years [14].
Sources: [11], [12], [13], [14]
Caveats: Observational. Cystatin C rises with inflammation, smoking and other conditions apart from kidney function [2][15], so a high level may mark illness already present.

Cystatin CStrong

Heart attack, stroke and heart failure in cohort studies

Linked to more cardiovascular disease at higher levels, about 82% more for each doubling of cystatin C across 16 pooled cohorts.

The numbers and sources

Effect: Across 16 prospective cohorts, the relative risk of cardiovascular disease was 1.82 per doubling of cystatin C (95% CI 1.56 to 2.13) after adjustment for age, sex and traditional risk factors [16]. In elderly US adults, the highest fifth of cystatin C (1.29 mg/L or above) against the two lowest (0.99 mg/L or below) had hazard ratios of 2.27 (95% CI 1.73 to 2.97) for cardiovascular death, 1.48 (1.08 to 2.02) for heart attack and 1.47 (1.09 to 1.96) for stroke, while the highest fifth of creatinine was not associated with any of the three [11]. Among elderly adults without chronic kidney disease, each 0.18 mg/L higher went with hazard ratios of 1.28 (1.17 to 1.40) for heart failure, 1.22 (1.08 to 1.38) for stroke and 1.20 (1.06 to 1.36) for heart attack [10]. In 23 outpatient cohorts, a cystatin C-based kidney estimate at least 30% below the creatinine-based one went with hazard ratios of 1.35 (1.27 to 1.44) for atherosclerotic cardiovascular disease and 1.54 (1.40 to 1.68) for heart failure [14].
Population: 76,481 participants in 16 cohorts, 37,126 with cystatin C measured [16]. 4,637 elderly adults followed from 1992 or 1993 to 2001 [11]. 4,663 elderly adults, 78% without chronic kidney disease, median follow-up 9.3 years [10]. 821,327 outpatients [14].
Sources: [16], [11], [10], [14]
Caveats: Observational. The genetic analysis in the next block was run to test whether this link is causal and did not support it [16].

Estimated GFR (eGFR)Strong

Death from any cause and from cardiovascular disease

Linked to more deaths at lower eGFR: against 95, risk was 18% higher at 60, 57% higher at 45 and about 3 times higher at 15.

The numbers and sources

Effect: In a collaborative meta-analysis of general population cohorts, risk of death was unrelated to eGFR between 75 and 105 mL/min/1.73 m2 and rose at lower values. Against an eGFR of 95, adjusted hazard ratios for death from any cause were 1.18 (95% CI 1.05 to 1.32) at 60, 1.57 (1.39 to 1.78) at 45 and 3.14 (2.39 to 4.13) at 15, with similar findings for cardiovascular death [6]. In a later individual-participant analysis of 114 cohorts, lower eGFR was significantly associated with higher all-cause and cardiovascular mortality, including in the mildest categories of chronic kidney disease [7].
Population: 105,872 participants in 14 studies with urine albumin-to-creatinine measurements and 1,128,310 in 7 studies with dipstick measurements [6]. 27,503,140 individuals in 114 cohorts, mean age 54, mean follow-up 4.8 years [7].
Sources: [6], [7]
Caveats: Observational. Urine albumin predicted death independently of eGFR, so eGFR alone gives part of the picture [6]. KDIGO notes that creatinine-based eGFR has a J-shaped association with most outcomes, with risk also rising above 105 mL/min/1.73 m2, and that very low creatinine often reflects frailty or low muscle mass [3].

Estimated GFR (eGFR)Strong

Kidney failure

Linked to far more kidney failure at lower eGFR: against 95, the hazard was 4 times higher at 60, 29 times at 45 and 454 times at 15.

The numbers and sources

Effect: In general population cohorts, risk of end-stage renal disease was unrelated to eGFR between 75 and 105 mL/min/1.73 m2 and rose exponentially below that. Against an eGFR of 95, hazard ratios were 4 at an eGFR averaging 60, 29 at 45 and 454 at 15, after adjustment for albuminuria and cardiovascular risk factors. Similar associations were found for acute kidney injury and progressive chronic kidney disease [8]. A later analysis of 114 cohorts found lower eGFR associated with higher risk of kidney failure requiring replacement therapy and of acute kidney injury [7].
Population: 845,125 participants in 9 general population cohorts and 173,892 patients in 8 cohorts at high risk of chronic kidney disease [8]. 27,503,140 individuals in 114 cohorts [7].
Sources: [8], [7]
Caveats: Observational. These are relative hazards, and the abstract gives no absolute rates. Urine albumin predicted kidney failure independently of eGFR [8].

HemoglobinStrong

Stroke, clots and death in kidney disease trials that raised hemoglobin

Shown in kidney disease trials: aiming for a higher hemoglobin with erythropoietin-type drugs raised stroke, blood pressure and access clotting, and did not lower deaths.

The numbers and sources

Effect: In a meta-analysis of 9 trials, a higher hemoglobin target carried a higher risk of death from any cause (risk ratio 1.17, 95% CI 1.01 to 1.35) and of clotting in the dialysis access (1.34, 1.16 to 1.54) than a lower target [12]. A later meta-analysis of 27 trials found that a higher target raised stroke (relative risk 1.51, 95% CI 1.03 to 2.21), hypertension (1.67, 1.31 to 2.12) and access clotting (1.33, 1.16 to 1.53). Differences in death (1.09, 0.99 to 1.20) and serious cardiovascular events (1.15, 0.98 to 1.33) did not reach significance [13].
Population: 5,143 patients with anemia from chronic kidney disease in 9 randomized trials [12]. 10,452 patients in 27 trials [13].
Sources: [12], [13]
Caveats: These trials raised hemoglobin with erythropoiesis-stimulating drugs in people with kidney disease, so they do not show what a higher hemoglobin reached another way does in other people. The second analysis could not separate the effect of the drug dose from the effect of the hemoglobin reached [13].

Hemoglobin A1c (HbA1c)Strong

Eye, kidney and nerve complications of diabetes

Shown in trials: intensive glucose control that lowered HbA1c about 0.9 points cut kidney events 20% and eye events 13% in type 2 diabetes.

The numbers and sources

Effect: In an individual-participant meta-analysis of 4 trials in type 2 diabetes, more intensive control left HbA1c 0.90 percentage points lower (95% CI 0.58 to 1.22) and reduced kidney events (HR 0.80, 95% CI 0.72 to 0.88) and eye events (HR 0.87, 95% CI 0.76 to 1.00), with no reduction in nerve events (HR 0.98, 95% CI 0.87 to 1.09) [11]. In type 1 diabetes, intensive therapy reduced the development of retinopathy by 76% (95% CI 62 to 85) and clinical neuropathy by 60% (95% CI 38 to 74) [12]. In an observational analysis of people with type 2 diabetes, each 1% lower updated mean HbA1c went with 37% fewer microvascular complications (95% CI 33 to 41), with no threshold [13]. In pooled data from nine studies, diabetes-specific retinopathy was rare below 6.0% and its threshold fell at 6.3 to 6.7% [14].
Population: 27,049 adults with type 2 diabetes in 4 trials, median follow-up 5.0 years [11]. 1,441 people with type 1 diabetes followed a mean 6.5 years [12]. 3,642 people with type 2 diabetes [13]. 28,010 people with HbA1c and retinal photographs [14].
Sources: [11], [12], [13], [14]
Caveats: The trials tested treatment strategies, not HbA1c itself. Intensive therapy raised severe hypoglycemia two to threefold in the type 1 diabetes trial [12].

KetoanaloguesStrong

Kidney function decline in chronic kidney disease

Shown to slow kidney function decline in adults with chronic kidney disease when added to a protein-restricted diet. Diet and supplement effects overlap.

The numbers and sources

Effect: In 16 RCTs (1,344 people with stage 3 to 5 CKD, median 13 months), ketoanalogues added to a protein-restricted diet gave a higher GFR than a low-protein diet alone, and a marginally lower risk of kidney failure in people without diabetes [1]. In 17 RCTs (1,459 participants), protein-restricted diets with ketoanalogues preserved eGFR and reduced proteinuria and blood pressure, with a larger eGFR effect on very low-protein diets [2]. In 10 RCTs and 2 non-randomized studies (951 patients), the combination delayed CKD progression (p 0.008), particularly with eGFR above 18 mL/min/1.73 m² [3]. In diabetic kidney disease, a review of 11 studies reported pooled GFR and urinary protein results in favor of ketoanalogues [4]. In non-diabetic adults with eGFR below 30, a ketoanalogue-supplemented vegetarian very low-protein diet for 15 months reduced the composite of starting dialysis or losing half of eGFR (number needed to treat 4.4) against a conventional low-protein diet [5].
Population: Adults with CKD stages 3 to 5 not on dialysis [1][2][3][5]. Adults with diabetic kidney disease not on dialysis [4].
Sources: [1], [2], [3], [4], [5]
Caveats: Many trials paired ketoanalogues with a stricter diet than the control arm, so the effects of diet and supplement overlap [2][5]. Only 14% of screened patients were randomized in [5]. The authors of [1] call for larger, longer trials, especially in diabetes. A Cochrane review of very low-protein diets, with or without ketoanalogues, found 165 fewer people per 1,000 reached kidney failure than on a low-protein diet (RR 0.65, 95% CI 0.49 to 0.85, moderate certainty) [6].

KetoanaloguesStrong

Phosphate and parathyroid hormone

Shown to lower blood phosphate, urea and parathyroid hormone in adults with chronic kidney disease on a protein-restricted diet.

The numbers and sources

Effect: Ketoanalogues added to a protein-restricted diet lowered blood urea nitrogen and phosphorus and raised calcium against a low-protein diet alone [1]. In 17 RCTs, they lowered serum phosphate and parathyroid hormone [2].
Population: Adults with CKD not on dialysis [1][2].
Sources: [1], [2]
Caveats: These are blood markers, not fractures or heart events.

SGLT2 inhibitorsStrongCommon

Kidney disease progression

Shown to cut the risk of kidney disease progression by about 37% in adults with chronic kidney disease, heart failure or type 2 diabetes, with or without diabetes.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Across 13 trials, allocation to an SGLT2 inhibitor lowered the risk of kidney disease progression by 37% (RR 0.63, 95% CI 0.58 to 0.69), with similar results in people with and without diabetes [4]. In 10 trials, progression occurred at 25.4 against 40.3 events per 1,000 patient-years (HR 0.62, 95% CI 0.57 to 0.68), including at an eGFR below 30 (HR 0.71, 95% CI 0.60 to 0.83), and kidney failure alone fell (HR 0.66, 95% CI 0.58 to 0.75) [5]. With dapagliflozin in chronic kidney disease, the primary kidney and cardiovascular outcome occurred in 9.2% against 14.5% on placebo over a median 2.4 years (HR 0.61, 95% CI 0.51 to 0.72, number needed to treat 19), and death from any cause in 4.7% against 6.8% [6]. With empagliflozin, kidney disease progression or cardiovascular death occurred in 13.1% against 16.9% over a median 2.0 years (HR 0.72, 95% CI 0.64 to 0.82) [7]. With canagliflozin in type 2 diabetes with kidney disease, the primary outcome occurred at 43.2 against 61.2 per 1,000 patient-years (HR 0.70, 95% CI 0.59 to 0.82), and end-stage kidney disease fell (HR 0.68, 95% CI 0.54 to 0.86) [8].
Population: 90,409 participants in 13 trials [4]; 70,361 participants in 10 trials, mean age 64.8 [5]; 4,304 adults with chronic kidney disease [6]; 6,609 adults with chronic kidney disease [7]; 4,401 adults with type 2 diabetes and albuminuric kidney disease [8].
Sources: [4], [5], [6], [7], [8]
Caveats: The two meta-analyses come from the same consortium and share trials [4][5]. The band above is the number needed to treat of 19 in one dapagliflozin trial [6]. Two of the kidney trials were stopped early [6][8]. The trials did not enroll people on dialysis.

Urine albumin to creatinine ratioStrong

Death from any cause and cardiovascular death

Linked to more deaths at higher ratios with no threshold, 63% more at about 30 mg/g than at about 5 mg/g across 105,872 people.

The numbers and sources

Effect: In a meta-analysis of general population cohorts, the ratio was related to death on a continuous scale without a threshold. Against a ratio of 0.6 mg/mmol (about 5 mg/g), the adjusted hazard ratio for death from any cause was 1.20 (95% CI 1.15 to 1.26) at 1.1 mg/mmol (10 mg/g), 1.63 (1.50 to 1.77) at 3.4 mg/mmol (about 30 mg/g) and 2.22 (1.97 to 2.51) at 33.9 mg/mmol (about 300 mg/g). Findings were similar for cardiovascular death, and the ratio and estimated GFR each added risk without interaction [5]. In a later meta-analysis of 114 cohorts, higher ratios were associated with higher rates of each of 10 outcomes studied: kidney failure, death from any cause, cardiovascular death, acute kidney injury, hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation and peripheral artery disease [8].
Population: 105,872 participants in 14 general population cohorts with ratio measurements [5]. 9,067,753 people with albuminuria data in 114 cohorts, with a median ratio of 11 mg/g in the main population [8].
Sources: [5], [8]
Caveats: Observational, with the ratio measured once at baseline. The first meta-analysis printed its ratios in mg/mmol, and the mg/g figures other than 10 are converted here with the factor on this page [5].

28 more

ACE inhibitorsModerate

Slowing kidney disease

Shown to slow kidney function loss in people with diabetic kidney disease and in non-diabetic kidney disease with protein in the urine.

The numbers and sources

Effect: In people with type 1 diabetes and kidney disease, serum creatinine doubled in 25 of 207 on captopril and 43 of 202 on placebo, a 48% reduction in risk. The combined risk of death, dialysis or transplantation fell 50% [11]. In individual data from 11 trials in mostly non-diabetic kidney disease, regimens with an ACE inhibitor lowered end-stage kidney disease (RR 0.69, 95% CI 0.51 to 0.94) and the combination of doubled creatinine or end-stage kidney disease (RR 0.70, 95% CI 0.55 to 0.88), with more benefit at higher urine protein [12]. A Cochrane review of 50 studies in diabetic kidney disease found ACE inhibitors and ARBs had similar benefits on kidney outcomes. Mortality against placebo did not differ significantly (RR 0.91, 95% CI 0.71 to 1.17) [13].
Population: 409 people with type 1 diabetes, urine protein of 500 mg a day or more [11]; 1,860 people without diabetes followed a mean of 2.2 years [12]; 13,215 people with diabetic kidney disease in 50 studies [13].
Sources: [11], [12], [13]
Caveats: The evidence in [11] is for captopril. Results were inconclusive for people with urine protein below 0.5 g a day [12].

Alpha-blockersModerateVery common

Stone fragments after shock wave lithotripsy

Shown to raise clearance of stone fragments after lithotripsy, from 69% to about 80%, in evidence a Cochrane review rated low certainty.

Compared with usual care alone or with placebo [13]

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Stone fragment clearance rose on an alpha-blocker plus usual care (RR 1.16, 95% CI 1.09 to 1.23), from 69.3% to an estimated 80.4%, or 111 more per 1,000. Auxiliary treatments fell from 9.7% to 6.5% (RR 0.67, 95% CI 0.45 to 1.00), major adverse events fell from 25.8% to 15.5% (RR 0.60), and clearance came 3.74 days sooner [13].
Population: 4,793 adults in 40 trials, only 4 of them placebo-controlled, mean stone size 7.1 to 13.2 mm [13].
Sources: [13]
Caveats: Low certainty evidence with high heterogeneity (I² 78%) [13]. Most trials used tamsulosin.

ARBs (angiotensin receptor blockers)Moderate

Kidney disease in type 2 diabetes

Shown to slow kidney disease in type 2 diabetes with protein in the urine, with 16 to 20% fewer people reaching kidney failure, doubled creatinine or death.

The numbers and sources

Effect: Over a mean 3.4 years, losartan lowered the composite of doubled creatinine, end-stage kidney disease or death by 16% against placebo (327 against 359 people). Doubled creatinine fell 25% and end-stage kidney disease 28%, with no effect on death [3]. Over a mean 2.6 years, irbesartan lowered the same composite by 20% against placebo and 23% against amlodipine, and doubled creatinine by 33% against placebo [4]. A Cochrane review of 50 studies found ACE inhibitors and ARBs had similar benefits on kidney outcomes, and ARBs did not lower mortality against placebo (RR 0.99, 95% CI 0.85 to 1.17) [5].
Population: 1,513 people with type 2 diabetes and kidney disease [3]; 1,715 people with high blood pressure and kidney disease from type 2 diabetes [4]; 13,215 people with diabetic kidney disease in 50 studies, 5 comparing ARBs with placebo [5].
Sources: [3], [4], [5]
Caveats: The trial evidence is for losartan and irbesartan. Both trials added the ARB to other blood pressure drugs.

Blood urea nitrogen (BUN)Moderate

Death in heart failure and after a heart attack

Linked to more deaths in people hospitalized with heart failure, about 2.3 times the risk in the top quarter of BUN in one cohort.

The numbers and sources

Effect: In 541 patients admitted for decompensated heart failure, the risk of death rose with each quartile of BUN, with an adjusted relative risk of 2.3 (95% CI 1.3 to 4.1) in the top against the bottom quartile [6]. In a US registry of heart failure admissions, a BUN of 43 mg/dL or above on admission was the single strongest predictor of death in hospital among 39 variables examined [4]. In older Medicare patients, adjusted 1-year mortality rose 3% per 5 mg/dL of BUN after a heart attack and 7% per 5 mg/dL in heart failure, with risk climbing steadily above 17 mg/dL and 16 mg/dL [7].
Population: 541 patients, mean age 63, followed for a mean of 343 days [6]. 33,046 hospitalizations in the derivation cohort and 32,229 in the validation cohort, mean age 72.5 [4]. 44,437 patients hospitalized for heart attack and 56,652 for heart failure, aged 65 or older [7].
Sources: [6], [4], [7]
Caveats: Observational, in people already in hospital with heart disease. The authors of the first study suggest that a raised BUN in this setting reflects reduced blood flow to the kidneys from the heart failure itself [6]. These cut points were derived to predict death in hospital patients and are not reference ranges.

CordycepsModerate

Kidney function

Shown to lower serum creatinine and urine protein when added to treatment in chronic kidney disease, in low-quality trials.

The numbers and sources

Effect: In a Cochrane review of 22 studies (1,746 participants), Cordyceps preparations added to conventional treatment lowered serum creatinine by 60.76 µmol/L (14 studies), raised creatinine clearance by 9.22 mL/min (6 studies) and cut 24-hour proteinuria by 0.15 g (4 studies) in people not on dialysis [6]. A 2025 meta-analysis of 15 studies (1,310 patients) with kidney dysfunction, including acute kidney injury, found Cordyceps sinensis as an add-on lowered blood creatinine, shortened the period of low urine output and raised urine osmolality [7].
Population: People with chronic kidney disease [6]; people with kidney dysfunction, including acute kidney injury [7].
Sources: [6], [7]
Caveats: Both reviews rest on low-quality trials. Risk of bias was high in 4 studies and unclear in 18, and the Cochrane authors could not reach definitive conclusions [6]. The 2025 review reported overall efficacy as diagnostic accuracy statistics, gives no size for the creatinine change in its abstract, and found results differed between northern and southern Chinese patients [7].

Cystatin CModerate

Kidney failure and new chronic kidney disease

Linked to later kidney disease: elderly adults with normal creatinine-based kidney function and cystatin C of 1.0 mg/L or above had 4 times the risk.

The numbers and sources

Effect: Among elderly adults without chronic kidney disease, those with cystatin C of 1.0 mg/L or above had a 4-fold risk of progressing to chronic kidney disease after 4 years, compared with those below 1.0 mg/L [10]. In a meta-analysis of 16 cohorts, reclassification to a lower kidney function category by cystatin C went with a higher risk of end-stage renal disease, with a net reclassification improvement of 0.10 (95% CI 0.00 to 0.21) [12]. In 23 outpatient cohorts, a cystatin C-based estimate at least 30% below the creatinine-based one went with a hazard ratio of 1.29 (95% CI 1.13 to 1.47) for kidney failure with replacement therapy [14].
Population: 4,663 elderly adults in a US community cohort [10]. 1,654 cases of end-stage renal disease in 7 cohorts [12]. 821,327 outpatients [14].
Sources: [10], [12], [14]
Caveats: Observational. Cystatin C is itself a measure of kidney filtration, so a higher level at the start may reflect kidney function already lower than creatinine showed.

Estimated GFR (eGFR)Moderate

The 2021 CKD-EPI creatinine equation against measured GFR

Shown to fall within 30% of measured GFR in 85% or more of people, reading a median 3.6 lower in Black and 3.9 higher in non-Black participants.

The numbers and sources

Compared with: GFR measured by clearance of an injected filtration marker
Effect: The 2021 equation, built from age, sex and creatinine with no race term, was tested in 12 studies. It underestimated measured GFR in Black participants by a median of 3.6 mL/min/1.73 m2 (95% CI 1.8 to 5.5) and overestimated it in non-Black participants by 3.9 (3.4 to 4.4). The earlier equation with a race term overestimated by 3.7 in Black participants and 0.5 in non-Black participants. For all equations, 85% or more of estimates were within 30% of measured GFR, and equations that add cystatin C were more accurate, with over 90% within 30% [10]. KDIGO treats 80% within 30% as acceptable and 90% as its higher target, and notes that at a true GFR of 60, a 30% error spans 42 to 78 mL/min/1.73 m2 [3].
Population: 4,050 participants in 12 validation studies, 14.3% Black. The equations were developed in 8,254 participants from 10 studies [10].
Sources: [10], [3]
Caveats: Compared with the earlier equation, the 2021 equation raised estimates of chronic kidney disease prevalence among Black adults and gave similar or lower prevalence among non-Black adults, so results from before and after a laboratory changed equations differ [10]. KDIGO reports very low accuracy for all estimating equations in people who are frail or severely ill [3].

Estimated GFR (eGFR)Moderate

Heart disease, stroke, heart failure and hospital admission

Linked to more coronary heart disease, stroke, heart failure, atrial fibrillation and hospital admissions at lower eGFR in an analysis of 114 cohorts.

The numbers and sources

Effect: In an individual-participant meta-analysis, lower eGFR was significantly associated with higher risk of each of 10 outcomes studied, among them coronary heart disease, stroke, heart failure, atrial fibrillation, peripheral artery disease and any hospitalization. Among people with a urine albumin-to-creatinine ratio below 10 mg/g, an eGFR of 45 to 59 against 90 to 104 mL/min/1.73 m2 went with more hospitalizations (adjusted HR 1.3, 95% CI 1.2 to 1.3), 161 against 79 events per 1,000 person-years [7].
Population: 27,503,140 individuals from 114 global cohorts with creatinine-based eGFR, and 720,736 from 20 cohorts with eGFR based on creatinine and cystatin C, from 1980 to 2021 [7].
Sources: [7]
Caveats: Observational and retrospective. The analysis used the 2021 CKD-EPI equations. Confounding by age and other illness may remain after adjustment [7].

Estimated GFR (eGFR)Moderate

Kidney outcomes in trials of treatments that slowed eGFR decline

Shown in trials: across 47 trials of 12 interventions, treatments that slowed the yearly fall in GFR also reduced kidney failure and doubling of creatinine.

The numbers and sources

Effect: In a meta-analysis of 47 randomized trials, a treatment's effect on the 3-year slope of GFR predicted its effect on the clinical endpoint of doubling of serum creatinine, GFR below 15 mL/min/1.73 m2 or end-stage kidney disease (median R squared 0.97, 95% Bayesian credible interval 0.78 to 1.00). A treatment effect of 0.75 mL/min/1.73 m2 per year or greater on slope predicted a clinical benefit with at least 96% probability, given a large enough trial [9].
Population: 60,620 participants in 47 randomized trials testing 12 interventions, in people with chronic kidney disease [9].
Sources: [9]
Caveats: The trials enrolled people with kidney disease and tested drugs and other treatments, so the finding does not describe people with eGFR in the reference range. It concerns the rate of change over years, not one result [9].

Ezetimibe and fenofibrateModerate

Fenofibrate and fibrates: protein in the urine

Shown to slow the progression of albumin in the urine, by 14% across fibrate trials, with less progression on fenofibrate in its main diabetes trial.

Compared with placebo [9][8]

The numbers and sources

Effect: Fibrates lowered the risk of albuminuria progression by 14% (95% CI 2 to 25) [9]. Fenofibrate was associated with less albuminuria progression in people with type 2 diabetes (p=0.002) [8].
Population: Fibrate trials [9]; 9,795 adults with type 2 diabetes [8].
Sources: [9], [8]
Caveats: Albuminuria is a marker of kidney damage, not kidney failure. Fenofibrate raises creatinine, listed under Risks.

InsulinModerate

Eye, kidney and nerve complications in type 1 diabetes

Shown to cut new eye disease by about 76%, kidney protein leakage by 39% to 54% and nerve damage by 60% with intensive insulin treatment in type 1 diabetes.

The numbers and sources

Effect: In people with type 1 diabetes and no eye disease, intensive insulin treatment lowered the risk of developing retinopathy by 76% (95% CI 62 to 85) against conventional treatment. In people with mild retinopathy it slowed progression by 54% (95% CI 39 to 66). Across both groups it lowered microalbuminuria by 39% (95% CI 21 to 52), albuminuria by 54% (95% CI 19 to 74) and clinical neuropathy by 60% (95% CI 38 to 74) [1]. A Cochrane review of 12 trials found retinopathy developed in 6.2% on intensive control against 23.2% on conventional control (RR 0.27, 95% CI 0.18 to 0.42), nephropathy in 16.3% against 28.4% (RR 0.56, 95% CI 0.46 to 0.68) and neuropathy in 4.9% against 13.9% (RR 0.35, 95% CI 0.23 to 0.53) [2].
Population: 1,441 people with type 1 diabetes, assigned to an insulin pump or three or more daily injections, or to one or two daily injections [1]; 2,230 patients in 12 trials followed for 1 to 6.5 years [2].
Sources: [1], [2]
Caveats: The trials compared more intensive with less intensive insulin treatment. Neither arm went without insulin. The largest trial dominates the review [2]. Once complications were present, the effect was weaker for eye disease and uncertain for kidney disease [2].

Uric acid (serum urate)Moderate

Kidney stones

Linked to more kidney stones in men in one large Korean cohort, 72% more at 10 mg/dL or above, with no such pattern in women.

The numbers and sources

Effect: In 239,331 Korean adults having health checkups, men with higher uric acid developed more kidney stones in a dose-response pattern. Against below 6.0 mg/dL, adjusted hazard ratios were 1.06 (95% CI 1.02 to 1.11) at 6.0 to 6.9 mg/dL, 1.11 (1.05 to 1.16) at 7.0 to 7.9, 1.21 (1.13 to 1.29) at 8.0 to 8.9, 1.31 (1.17 to 1.46) at 9.0 to 9.9 and 1.72 (1.44 to 2.06) at 10.0 or above. No dose-response association was seen in women [13]. An umbrella review found that the one trial outcome with robust evidence for urate-lowering treatment was fewer recurrences of kidney stones [12].
Population: 239,331 adults with 18,777 new cases of kidney stones found on ultrasound [13]. 31 meta-analyses of randomized trials within the umbrella review [12].
Sources: [13], [12]
Caveats: The cohort is observational, had no dietary data and did not use CT to confirm stones [13].

Urine albumin to creatinine ratioModerate

Kidney failure

Linked to kidney failure, with a 30% fall in the ratio over 2 years tied to 17% lower risk of end-stage kidney disease across 28 cohorts.

The numbers and sources

Effect: In an individual-level meta-analysis, a 30% decrease in the ratio over 2 years was followed by a lower risk of end-stage kidney disease (adjusted HR 0.83, 95% CI 0.74 to 0.94, and 0.78 after correction for measurement variability). The association was stronger at higher starting ratios. In people starting at 300 mg/g or higher, a 30% fall was estimated to lower the 10-year risk of end-stage kidney disease by more than 1 percentage point [10]. A kidney guideline states that in large population studies a doubling of the ratio within 2 years is associated with a 50% to 100% higher risk of progression to kidney failure [4].
Population: 693,816 people in 28 cohorts, 80% with diabetes, with 7,461 end-stage kidney disease events [10].
Sources: [10], [4]
Caveats: Observational. A fall in the ratio in these cohorts had many causes, and the analysis does not show that lowering the ratio by any particular means changes the outcome [10].

Urine albumin to creatinine ratioModerate

Kidney outcomes in trials of treatments that lowered albuminuria

Shown across 41 trial comparisons that treatments lowering albuminuria by 30% went with 27% fewer kidney endpoints, less certain when starting albuminuria was low.

The numbers and sources

Effect: A meta-analysis related each treatment's effect on albuminuria at 6 months to its effect on a composite of end-stage kidney disease, estimated GFR below 15 mL/min per 1.73 m² or doubling of serum creatinine. Each 30% decrease in albuminuria relative to control was associated with an average 27% lower hazard of the composite (95% credible interval 5% to 45%). The association was stronger in patients with starting albuminuria above 30 mg/g [11].
Population: 29,979 participants in 41 treatment comparisons from randomized trials, 71% with diabetes, followed for a median of 3.4 years [11].
Sources: [11]
Caveats: A comparison across trials of different drugs, with a wide credible interval. The authors describe the association as less certain for patients with low albuminuria at baseline [11].

AlbuterolLimited

Lowering high blood potassium

Small studies found inhaled and nebulized beta-agonists lowered blood potassium in hyperkalemia, and adding insulin with glucose lowered it more than either alone.

Compared with control groups in small trials, which the abstract does not describe [9]

The numbers and sources

Effect: Inhaled and nebulized beta-agonists and intravenous insulin with glucose all lowered serum potassium, and nebulized beta-agonists combined with insulin and glucose lowered it more than either alone. No study reported deaths or heart rhythm problems [9].
Population: Small randomized studies of emergency treatments for hyperkalemia [9].
Sources: [9]
Caveats: Many studies were small, and the abstract gives no effect sizes. This is a hospital use, not one on the inhaler label [9].

AllopurinolLimited

Uric acid during cancer treatment

One trial found 66% of adults at risk of tumor lysis syndrome kept uric acid controlled on allopurinol, against 87% on rasburicase.

The numbers and sources

Effect: In adults with blood cancers, plasma uric acid stayed at or fell to 7.5 mg/dL or below during days 3 to 7 in 66% on oral allopurinol 300 mg a day, 87% on intravenous rasburicase and 78% on rasburicase followed by allopurinol. In those who started with high uric acid, control took 27 hours on allopurinol and 4 hours on rasburicase [7].
Population: 275 adults with blood cancers at risk of high uric acid and tumor lysis syndrome, 91 of them on allopurinol alone [7].
Sources: [7]
Caveats: One trial with no placebo group, measuring uric acid and not kidney injury.

AllopurinolLimited

Preventing calcium oxalate kidney stones

One trial found fewer kidney stone events on allopurinol, 0.12 against 0.26 per patient a year, in people with high urinary uric acid.

The numbers and sources

Effect: In people with recurrent calcium oxalate stones, high urinary uric acid and normal urinary calcium, stone events occurred at 0.12 per patient a year on allopurinol 100 mg three times a day and 0.26 on placebo, and time to recurrence was longer on allopurinol. Against their own history, stones fell 81.2% on allopurinol and 63.4% on placebo [8].
Population: 60 people with a history of calcium oxalate stones [8].
Sources: [8]
Caveats: One small trial from 1986. Stones also fell 63.4% in the placebo group, which the authors attribute to the bias of comparing people against their own history [8].

Blood urea nitrogen (BUN)Limited

Type 2 diabetes

One cohort of 1.3 million US veterans found 23% more new diabetes with BUN above 25 mg/dL than at 25 or below.

The numbers and sources

Effect: In 1,337,452 US veterans without diabetes followed for a median of 4.93 years, a BUN over 25 mg/dL went with more new diabetes than a BUN of 25 mg/dL or less (hazard ratio 1.23, 95% CI 1.21 to 1.25), with eGFR in the model. The association held at every level of eGFR, including 60 mL/min/1.73 m2 or more (hazard ratio 1.27, 95% CI 1.24 to 1.31). Each 10 mg/dL higher BUN went with a hazard ratio of 1.15 (1.14 to 1.16) [8].
Population: 1,337,452 US veterans, with 172,913 new cases of diabetes [8].
Sources: [8]
Caveats: Observational, one cohort of US veterans. The cut point of 25 mg/dL was the study's analysis category, not a reference range [8].

Blood urea nitrogen (BUN)Limited

Kidney failure in people with chronic kidney disease

One study of 459 people with stage 3 to 5 kidney disease found more kidney failure or death in the top quarter of BUN, independent of eGFR.

The numbers and sources

Effect: In 459 Japanese patients with chronic kidney disease stages 3 to 5 followed for a median of 25.8 months, hazard ratios for end-stage renal disease or death in the second, third and fourth quartiles of BUN against the first were 1.36 (95% CI 0.72 to 2.58), 1.87 (0.95 to 3.66) and 2.66 (1.23 to 5.76), after adjustment that included eGFR. Higher BUN quartiles also carried more risk of end-stage renal disease alone [9].
Population: 459 patients with chronic kidney disease stages 3 to 5, of whom 210 reached the endpoint [9].
Sources: [9]
Caveats: Observational, one cohort in one country. Only the top quartile differed significantly from the bottom [9].

DulaglutideLimited

Kidney outcomes in type 2 diabetes

One large trial found a 15% lower rate of a combined kidney outcome on dulaglutide, mostly from less new heavy protein in the urine.

Compared with placebo [7]

The numbers and sources

Effect: The kidney outcome, new macroalbuminuria, a sustained 30% or greater fall in eGFR, or chronic kidney replacement, occurred in 17.1% on dulaglutide and 19.6% on placebo (HR 0.85, 95% CI 0.77 to 0.93). New macroalbuminuria fell (HR 0.77, 95% CI 0.68 to 0.87), while the eGFR decline (HR 0.89, 95% CI 0.78 to 1.01) and kidney replacement therapy (HR 0.75, 95% CI 0.39 to 1.44) did not differ significantly [7].
Population: 9,901 adults with type 2 diabetes in REWIND, mean eGFR 76.9, followed a median 5.4 years [7].
Sources: [7]
Caveats: An exploratory analysis of a cardiovascular trial, funded by the manufacturer [7].
Why limited: This rests on one trial, of 9,901 people. Strength counts independent studies that agree, so one trial is limited at any size.

FructosamineLimited

Eye and kidney complications

One US cohort linked fructosamine above the 95th percentile to 50% more new chronic kidney disease, and higher levels to more retinopathy.

The numbers and sources

Effect: Fructosamine and glycated albumin were strongly associated with retinopathy (P below 0.0001 for trend). The adjusted hazard ratio for chronic kidney disease was 1.50 (95% CI 1.22 to 1.85) for fructosamine above the 95th percentile and 1.48 (1.20 to 1.83) for glycated albumin, compared with people without diabetes below the 75th percentile. Prediction of chronic kidney disease was nearly as strong as with HbA1c, with C statistics of 0.717, 0.717 and 0.726 [5].
Population: 11,348 adults without diabetes and 958 with diagnosed diabetes, followed for two decades [5].
Sources: [5]
Caveats: Observational, from one cohort. A laboratory guideline states that few published studies have convincingly shown a relationship between glycated protein levels and the chronic complications of diabetes [2].

Parathyroid hormone (PTH)Limited

Kidney function

One study found PTH differed across tenths of kidney function in 1,814 patients, and 12% of those with an eGFR above 80 already had high PTH.

The numbers and sources

Effect: In outpatients tested across 153 centers, mean and median PTH differed significantly across deciles of estimated glomerular filtration rate (P below 0.001). High PTH, defined as above 65, was present in 12% of patients with an eGFR above 80 mL/min, while calcium and phosphorus stayed normal until eGFR fell below 40 [10]. Kidney guidelines set separate PTH targets for people on dialysis: the National Kidney Foundation's KDOQI guidelines used 150 to 300 pg/mL for stage 5 chronic kidney disease [11], and the KDIGO guideline uses two to nine times the upper limit of the assay [9]. The 2017 KDIGO update bases treatment on trends in results and not on a single abnormal value [12].
Population: 1,814 patients with a mean age of 71.1, 48% with diabetes [10].
Sources: [10], [11], [9], [12]
Caveats: Cross-sectional, in older patients, and the abstract misprints the unit of its PTH cut point. The dialysis targets are treatment targets for kidney failure and are not reference ranges. The KDIGO target is a multiple of each assay's upper limit, a different quantity from a result in pg/mL, so it has no band on this page.

SemaglutideLimited

Kidney disease in type 2 diabetes

One trial found a 24% lower risk of major kidney events, and fewer deaths, in adults with type 2 diabetes and chronic kidney disease.

The numbers and sources

Effect: Major kidney disease events (kidney failure, a fall in eGFR of 50% or more, or death from kidney or cardiovascular causes) occurred in 331 people on semaglutide and 410 on placebo (HR 0.76, 95% CI 0.66 to 0.88). The kidney-specific events alone gave HR 0.79 (95% CI 0.66 to 0.94). eGFR declined 1.16 mL/min/1.73 m2 a year more slowly, cardiovascular death was lower (HR 0.71, 95% CI 0.56 to 0.89) and death from any cause was lower (HR 0.80, 95% CI 0.67 to 0.95) [6].
Population: 3,533 adults with type 2 diabetes and chronic kidney disease with raised urine albumin, 1.0 mg weekly, median follow-up 3.4 years [6].
Sources: [6]
Caveats: One trial, stopped early after a prespecified interim analysis. Funded by Novo Nordisk. It enrolled people with type 2 diabetes, so it does not describe kidney disease without diabetes [6].
Why limited: This rests on one trial, of 3,533 people. Strength counts independent studies that agree, so one trial is limited at any size.

Serum creatinineLimitedStudied in men

Stroke and death at higher levels

Limited evidence: one British cohort of 7,690 middle-aged men linked creatinine above 1.31 mg/dL to 60% more strokes over about 15 years.

The numbers and sources

Effect: Median creatinine was 98 µmol/L (1.11 mg/dL). Above 116 µmol/L (1.31 mg/dL), the top tenth, the relative risk of stroke was 1.6 (95% CI 1.1 to 2.1) against all other men after adjustment for cardiovascular risk factors. For major ischemic heart disease, the relative risk at 130 µmol/L (1.47 mg/dL) or above was 1.2 (0.8 to 1.7) after adjustment. Death from any cause and from cardiovascular disease was significantly raised only above the 97.5th percentile, and there was no association with death from cancer [6].
Population: 7,690 men aged 40 to 59 from 24 British towns, followed for an average of 14.75 years, with 287 strokes, 967 major ischemic heart disease events and 1,259 deaths [6].
Sources: [6]
Caveats: One observational cohort of middle-aged men in one country [6]. Studies that convert creatinine to an estimated filtration rate are covered on the eGFR page.

Serum creatinineLimited

Death in hospital after a rise during the stay

Limited evidence: in one hospital cohort a rise in creatinine of 0.5 mg/dL or more during the stay went with 6.5 times the odds of death.

The numbers and sources

Effect: Among adults with two or more creatinine results during a hospital stay, a rise of 0.5 mg/dL or more occurred in 1,237 (13%) and a rise of 2.0 mg/dL or more in 105 (1%). A rise of 0.5 mg/dL or more was associated with 6.5 times the odds of death (95% CI 5.0 to 8.5), 3.5 more days in hospital and nearly 7,500 dollars in added cost, after adjustment for age, sex, diagnosis, severity of illness and chronic kidney disease [7].
Population: 9,210 adults with two or more creatinine measurements, among 19,982 admitted to one urban academic medical center [7].
Sources: [7]
Caveats: Observational, at one center, in people ill enough to be admitted. It concerns a change during a hospital stay, not a single outpatient result [7].

SulfonylureasLimited

Eye, kidney and other small-vessel complications

One trial found 25% fewer small-vessel complications over 10 years with intensive sulfonylurea or insulin treatment than with diet in newly diagnosed type 2 diabetes.

The numbers and sources

Effect: Against diet, intensive treatment with a sulfonylurea or insulin lowered any diabetes-related endpoint by 12% (95% CI 1 to 21) and microvascular endpoints by 25% (95% CI 7 to 40), including the need for retinal laser treatment. Results did not differ between chlorpropamide, glibenclamide and insulin. Diabetes-related death (10% lower, 95% CI -11 to 27) and death from any cause (6% lower, 95% CI -10 to 20) did not differ significantly [4].
Population: 3,867 newly diagnosed patients with type 2 diabetes, median age 54, followed over 10 years [4].
Sources: [4]
Caveats: The trial pooled sulfonylureas with insulin in its intensive group, and used chlorpropamide, glibenclamide and glipizide. It did not find fewer large-vessel events [4].
Why limited: This rests on one trial, of 3,867 people. Strength counts independent studies that agree, so one trial is limited at any size.

Total iron binding capacity (TIBC)Limited

Death in people on hemodialysis

Limited evidence: one cohort of 807 hemodialysis patients linked a lower TIBC, and a fall in TIBC over 6 months, to more deaths.

The numbers and sources

Effect: Mortality rose step by step across lower TIBC groups. The adjusted hazard ratio for death was 1.75 (95% CI 1.00 to 3.05) for a TIBC below 150 against 200 to 250, and a fall of more than 20 over 6 months had a hazard ratio of 1.57 (1.04 to 2.36) against a stable result. Patients with a TIBC of 250 or above had a higher body mass index, more arm muscle and fat by skinfold, higher serum iron, and lower ferritin and inflammatory markers [7].
Population: 807 people on maintenance hemodialysis in a prospective 5-year cohort [7].
Sources: [7]
Caveats: One observational cohort in people on dialysis, in whom the authors treat TIBC as a marker of protein and energy wasting, so it does not describe people without kidney failure. The abstract prints the TIBC values in mg/dL, and the figures above are given as printed. The lower limit of the hazard ratio for a low TIBC is 1.00 [7].

Urine albumin to creatinine ratioLimited

Cardiovascular events at ratios below 30 mg/g

One cohort of 1,568 adults without diabetes or high blood pressure linked ratios above the group's median, far below 30 mg/g, to nearly three times the cardiovascular events.

The numbers and sources

Effect: Participants with a ratio at or above the sex-specific median (3.9 mg/g for men, 7.5 mg/g for women) had a hazard ratio of 2.92 (95% CI 1.57 to 5.44) for a first cardiovascular event against those below the median, and 1.75 (0.95 to 3.22) for death. The finding held when people with a ratio of 30 mg/g or more were excluded [9].
Population: 1,568 adults in the Framingham Offspring Study, mean age 55, free of cardiovascular disease, hypertension and diabetes, followed for a median of 6 years, with 54 first cardiovascular events [9].
Sources: [9]
Caveats: One cohort with 54 events and wide intervals. The larger pooled analyses above also found risk rising below 30 mg/g [5].

Reported risks75

ACE inhibitorsModerateVery common

With an ARB or aliskiren

Shown to raise high potassium, low blood pressure and kidney failure when an ACE inhibitor is combined with an ARB or aliskiren, with no fewer deaths.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Across 33 trials, combining two blockers of the renin-angiotensin system did not lower all-cause mortality against one (RR 0.97, 95% CI 0.89 to 1.06) and raised hyperkalemia by 55%, low blood pressure by 66% and kidney failure by 41% [26]. In ONTARGET, ramipril plus telmisartan brought more low blood pressure symptoms (4.8% against 1.7%), fainting (0.3% against 0.2%) and kidney dysfunction (13.5% against 10.2%) than ramipril alone, with no difference in cardiovascular events (16.3% against 16.5%) [15]. In people with diabetic kidney disease, lisinopril added to losartan raised hyperkalemia (6.3 against 2.6 events per 100 person-years) and acute kidney injury (12.2 against 6.7), and the trial was stopped early [27].
Population: 68,405 people in 33 trials, mean 52 weeks [26]; 17,078 people assigned to the combination or ramipril alone [15]; 1,448 people with type 2 diabetes and kidney disease [27].
Sources: [26], [15], [27]
Caveats: Hospital admissions for heart failure fell 18% on dual therapy in the pooled analysis [26]. The lisinopril label describes the same findings [3].

ARBs (angiotensin receptor blockers)ModerateVery common

With an ACE inhibitor or aliskiren

Shown to raise high potassium, low blood pressure and kidney failure when an ARB is combined with an ACE inhibitor or aliskiren, with no fewer deaths.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Across 33 trials, combining two blockers of the renin-angiotensin system did not lower all-cause mortality against one (RR 0.97, 95% CI 0.89 to 1.06) and raised hyperkalemia by 55%, low blood pressure by 66% and kidney failure by 41% [36]. In ONTARGET, telmisartan plus ramipril brought more low blood pressure symptoms (4.8% against 1.7%) and kidney dysfunction (13.5% against 10.2%) than ramipril alone [16]. In people with diabetic kidney disease on losartan, adding lisinopril raised hyperkalemia (6.3 against 2.6 events per 100 person-years) and acute kidney injury (12.2 against 6.7), and the trial was stopped early [37].
Population: 68,405 people in 33 trials, mean 52 weeks [36]; 17,078 people assigned to the combination or ramipril alone [16]; 1,448 people with type 2 diabetes and kidney disease [37].
Sources: [36], [16], [37]
Caveats: Hospital admissions for heart failure fell 18% on dual therapy in the pooled analysis [36]. The losartan label carries the same warning [10].

TopiramateModerateVery common

Metabolic acidosis

The label reports that topiramate lowers blood bicarbonate, in up to 67% of children in trials against 10% on placebo, and by about 4 mEq/L in adults at 400 mg.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Topiramate causes a non-anion gap metabolic acidosis through bicarbonate loss in the kidney. Bicarbonate fell by an average of 4 mEq/L at 400 mg a day in adults. In children's add-on trials, a decreased bicarbonate occurred in up to 67% on topiramate and 10% on placebo, and a markedly low value in up to 11% against 2% or less. The label states chronic acidosis may raise the risk of kidney stones and bone loss and slow growth in children [3].
Population: Adults and children in clinical trials [3].
Sources: [3]
Caveats: The highest rates were in children at about 6 mg/kg a day. Severe drops below 10 mEq/L were rare [3].

ACE inhibitorsModerateCommon

Kidney function changes

Shown to raise creatinine in some people, with kidney dysfunction in 2.4% on lisinopril against 1.1% of controls after a heart attack.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Minor, reversible rises in blood urea nitrogen and creatinine occurred in about 2% of people with hypertension on lisinopril alone and in 11.6% of people with heart failure also taking a diuretic. In GISSI-3, kidney dysfunction, defined as creatinine above 3 mg/dL or doubled, occurred in 2.4% on lisinopril and 1.1% of those not given it. In ATLAS, raised creatinine was reported in 10% on the high dose and 7% on the low dose. The label warns that acute kidney failure can occur, particularly with renal artery stenosis, chronic kidney disease, severe heart failure or volume depletion [3].
Population: People in lisinopril clinical trials, including 19,394 in GISSI-3 and 3,164 in ATLAS [3].
Sources: [3]
Caveats: Rises were more frequent with diuretics and often resolved when the diuretic dose was lowered [3]. For the long-term effect on kidney disease, see the kidney outcome block above.

ARBs (angiotensin receptor blockers)ModerateCommon

Kidney function changes

Shown to raise creatinine in some people with heart failure, by more than half in 3.9% on valsartan against 0.9% on placebo.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: In heart failure trials, creatinine rose by more than 50% in 3.9% on valsartan and 0.9% on placebo. After a heart attack, creatinine doubled in 4.2% on valsartan and 3.4% on captopril [14]. The losartan label warns that acute kidney failure can occur, particularly with renal artery stenosis, chronic kidney disease, severe heart failure or volume depletion [10].
Population: People in valsartan heart failure and heart attack trials [14].
Sources: [14], [10]
Caveats: For the long-term effect on diabetic kidney disease, see the kidney outcome block above.

BisphosphonatesModerateStudied in womenCommon

Kidney function after zoledronic acid

The label warns zoledronic acid can impair kidney function, with a short-lived creatinine rise within 10 days in 1.8% against 0.8% on placebo.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: A transient rise in serum creatinine within 10 days of dosing occurred in 1.8% on zoledronic acid and 0.8% on placebo and resolved without treatment. Changes in creatinine clearance over 3 years and rates of kidney failure were comparable to placebo. The label reports rare acute kidney failure and contraindicates it below a creatinine clearance of 35 mL/min [13].
Population: Women in the main osteoporosis trial, which excluded creatinine clearance under 30 mL/min [13].
Sources: [13]
Caveats: People with poorer kidney function were excluded from the trial.

SGLT2 inhibitorsModerateCommon

Low blood pressure and fluid loss

Shown to cause fluid loss reactions such as low blood pressure and fainting in 2.3% to 3.4% on canagliflozin against 1.5% on comparators, more often with age over 75.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: In eight pooled canagliflozin trials, at least one volume depletion reaction occurred in 2.3% on 100 mg and 3.4% on 300 mg against 1.5% on comparators. In people aged 75 and older the rates were 4.9% and 8.7% against 2.6%, and in people on a loop diuretic 3.2% and 8.8% against 4.7%. In the canagliflozin kidney trial, hypotension occurred in 2.8% against 1.5% on placebo [24]. In pooled empagliflozin trials, these reactions were reported by 0.5% on 10 mg and 0.3% on 25 mg against 0.3% on placebo, and the label states that diuretics taken with empagliflozin raised urine volume and may add to fluid loss [20]. In the dapagliflozin heart failure trial, volume depletion events did not differ from placebo [2].
Population: Adults in eight pooled canagliflozin trials and 2,201 on canagliflozin in the kidney trial [24]; 2,971 adults in five empagliflozin trials [20]; 4,744 adults with heart failure [2].
Sources: [24], [20], [2]
Caveats: Rates differed widely between drugs and trial pools, from no excess to about double.

Keto dietLimitedCommon

Kidney stones

Linked to kidney stones in about 6% to 14% of children treated for epilepsy in clinic cohorts.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: At one hospital, kidney stones occurred in about 6% of children started on the diet. Among 313 children, 11 of 105 (10.5%) not given potassium citrate developed stones, against 4 of 198 (2.0%) given it [18]. In another cohort, 11 of 80 children (13.8%) had kidney stones or calcium deposits, all on the classic diet and none on the modified Atkins diet [19]. One trial reported more high urine calcium on the classic diet than on the modified Atkins diet [8].
Population: Children with drug-resistant epilepsy, observational clinic cohorts [18][19].
Sources: [8], [18], [19]
Caveats: Observational studies in children on a medical diet, often alongside antiseizure drugs. Rates in adults following the diet for weight loss were not located.

Loop diureticsLimitedCommon

Kidney function

Linked to small rises in creatinine and urea, with raised creatinine in 7.4% of bumetanide patients tested. High furosemide doses caused transient worsening of kidney function in one trial.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Torsemide 10 mg a day for 6 weeks raised blood urea nitrogen a mean 1.8 mg/dL and creatinine 0.05 mg/dL, reversing after stopping [1]. Raised creatinine was reported in 7.4% and raised urea (azotemia) in 10.6% of patients tested on bumetanide [15]. In acute heart failure, the high-dose furosemide strategy brought transient worsening of kidney function [2].
Population: Hypertensive patients [1]; bumetanide-treated patients [15]; 308 patients [2].
Sources: [1], [15], [2]
Caveats: Creatinine changes during fluid removal can reflect less blood volume rather than kidney damage. No placebo group for the bumetanide figures.

Muscle relaxantsLimitedCommon

Baclofen in kidney disease: confusion

Linked to hospital admission with confusion within 30 days in older adults with kidney disease, in 1.11% at 20 mg a day or more against 0.42% at lower doses.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Among older adults with chronic kidney disease newly prescribed baclofen, admission with encephalopathy within 30 days occurred in 1.11% of those started at 20 mg a day or more and 0.42% of those started lower (weighted RR 3.54, 95% CI 2.24 to 5.59). The excess rose as kidney function fell, to 2.90 percentage points at an eGFR below 30. Against non-users, risk was higher at both doses (RR 5.90 and 19.8) [17]. The baclofen label states that the drug is mainly excreted unchanged by the kidneys [14].
Population: 15,942 adults aged 66 or older in Ontario with an eGFR below 60 and not on dialysis, and 284,263 non-users [17].
Sources: [17], [14]
Caveats: Observational, in older adults from one province.

TopiramateLimitedCommon

Kidney stones

The label reports kidney stones in 1.5% of adults in add-on epilepsy trials, about 2 to 4 times the rate expected in a similar untreated population.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Kidney stones occurred in 1.5% of adults in add-on epilepsy trials, more often in men. In an open-label extension in infants aged 1 to 24 months, 7% developed kidney or bladder stones within a year. Topiramate lowers urinary citrate and raises urinary pH [3].
Population: Adults in epilepsy trials and 284 infants in an open-label extension [3].
Sources: [3]
Caveats: Compared with an expected rate, not a placebo group.

Calcium channel blockersLimitedUncommon

With clarithromycin

Linked to more hospital stays for acute kidney injury in older adults given clarithromycin while on a calcium channel blocker, 0.44% against 0.22% with azithromycin.

The numbers and sources

How common: Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect: Within 30 days of a new prescription, hospitalization with acute kidney injury occurred in 0.44% of those given clarithromycin and 0.22% of those given azithromycin. The risk was highest with nifedipine (OR 5.33, 95% CI 3.39 to 8.38). Hospitalization with low blood pressure (0.12% against 0.07%, OR 1.60) and death from any cause (1.02% against 0.59%, OR 1.74, 95% CI 1.57 to 1.93) were also more frequent [21].
Population: Ontario adults with a mean age of 76 on amlodipine, felodipine, nifedipine, diltiazem or verapamil, 96,226 given clarithromycin and 94,083 given azithromycin [21].
Sources: [21]
Caveats: Observational, in older adults. More than half were on amlodipine.

63 more

ARBs (angiotensin receptor blockers)LimitedRare

With NSAIDs

Linked to more acute kidney injury when an NSAID is taken with both a diuretic and an ARB or ACE inhibitor, about 31% higher in one cohort.

The numbers and sources

How common: Rare: fewer than 1 in 1,000 people.
Effect: Among users of blood pressure drugs, current use of an NSAID with both a diuretic and an ARB or ACE inhibitor was associated with a higher rate of acute kidney injury (rate ratio 1.31, 95% CI 1.12 to 1.53), highest in the first 30 days (1.82, 95% CI 1.35 to 2.46). An NSAID with only one of those drugs was not associated with a higher rate. Acute kidney injury occurred at 7 per 10,000 person-years in the cohort [38]. The losartan label states that NSAIDs taken with ARBs may worsen kidney function in people who are elderly, volume-depleted or have impaired kidneys, and may weaken the blood pressure effect [10].
Population: 487,372 users of blood pressure drugs in UK general practice, mean follow-up 5.9 years [38].
Sources: [38], [10]
Caveats: Observational. The rate is for the whole cohort, not only people on the three-drug combination [38].

Thiazide diureticsLimitedRare

With NSAIDs

Linked to more acute kidney injury when an NSAID is taken with both a diuretic and an ACE inhibitor or ARB. The label says NSAIDs can blunt the diuretic.

The numbers and sources

How common: Rare: fewer than 1 in 1,000 people.
Effect: Among users of blood pressure drugs, an NSAID with both a diuretic and an ACE inhibitor or ARB was associated with a higher rate of acute kidney injury (rate ratio 1.31, 95% CI 1.12 to 1.53), highest in the first 30 days (1.82). An NSAID with a diuretic alone was not associated with a higher rate. Acute kidney injury occurred at 7 per 10,000 person-years in the cohort [26]. The hydrochlorothiazide label states that NSAIDs can reduce the diuretic and blood pressure effects of thiazides [14].
Population: 487,372 users of blood pressure drugs in UK general practice, mean follow-up 5.9 years [26].
Sources: [26], [14]
Caveats: Observational. The study did not separate thiazides from other diuretics, and the rate is for the whole cohort [26].

CreatineStrongHow often is not known

Raised serum creatinine and kidney markers

Shown to raise blood creatinine, which lowers kidney estimates based on it. Kidney function measured another way did not change.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In 26 RCTs (1,036 participants), serum creatinine rose 0.14 mg/dL (95% CI 0.05 to 0.22, I² 93.9%) and creatinine-based GFR estimates fell 10.75 mL/min (95% CI -17.48 to -4.02). GFR measured with Cr-EDTA, which does not rely on creatinine, did not differ (5.89 mL/min, 95% CI -0.30 to 12.08), nor did urea, albuminuria or proteinuria [18]. In 20 randomized trials, serum creatinine rose 0.13 mg/dL (95% CI 0.07 to 0.18), and urea and eGFR did not differ (eGFR -5.20 mL/min/1.73 m², 95% CI -15.00 to 4.60) [19]. In 12 studies (440 participants), serum creatinine rose by a mean of 0.07 (95% CI 0.01 to 0.12), significant at 1 week or less and after 12 weeks but not at 1 to 12 weeks. Glomerular filtration rate did not differ from control [20].
Population: Healthy people and people with chronic kidney disease, including a hemodialysis subgroup [18]; 19 RCTs and one crossover trial [19]; mostly healthy adults, 177 on creatine and 263 controls in the creatinine analysis [20].
Sources: [18], [19], [20]
Caveats: Creatinine is a breakdown product of creatine, so a higher reading and a lower creatinine-based GFR estimate can occur without a change in filtration. The authors of [18] attribute the changes to altered creatinine metabolism, since Cr-EDTA GFR did not change. The 2025 abstract reports its creatinine difference in µmol/L, a unit at which 0.07 would be negligible, and the unit may be a reporting error [20]. The authors of [19] call for trials longer than 1 year.

High-protein dietStrongHow often is not known

Kidney function in people without kidney disease

Shown to raise kidney filtration rate, urea and urine calcium in people without kidney disease, with no consistent sign of kidney injury in mostly short trials.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Across 30 studies (2,160 people), GFR rose 7.18 mL/min/1.73 m² more on high-protein diets (95% CI 4.45 to 9.91), with higher serum urea (1.75 mmol/L), urinary calcium (25.43 mg a day) and serum uric acid [11]. In 22 RCTs, eGFR rose (SMD 0.39, 95% CI 0.09 to 0.69, I² 74.9%) and serum creatinine did not change (SMD 0.08, 95% CI -0.09 to 0.25) [5]. In 28 trials (1,358 people), GFR after the diet was slightly higher (SMD 0.19, 95% CI 0.07 to 0.31), and the change in GFR did not differ (SMD 0.11, 95% CI -0.05 to 0.27) [9].
Population: Adults without chronic kidney disease in randomized trials [5][9][11].
Sources: [5], [9], [11]
Caveats: Most trials were short and used creatinine-based estimates, so long-term effects are uncertain [5]. Cohorts disagree: in 9,226 Korean adults, the highest protein quarter was linked to 1.32 times the risk of rapid eGFR decline (95% CI 1.02 to 1.73) [12], while a meta-analysis of 6 cohorts (148,051 people) linked higher protein to lower chronic kidney disease incidence (RR 0.82, 95% CI 0.71 to 0.94) [13].

Black seed oilModerateHow often is not known

Liver and kidney markers in trials

Liver and kidney markers did not worsen in most trials. Creatinine rose slightly in 3 trials, and doses above 2,000 mg a day were linked to a BUN change.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In 19 trials (1,295 participants), Nigella sativa lowered ALP by 10.8 U/L and BUN by 1.016. Creatinine rose by 0.070 in 3 trials with covariate-adjusted analyses, and doses above 2,000 mg a day were linked to a BUN change in 2 trials [11]. In 70 healthy adults given 200 mg a day of a thymoquinone-rich oil for 90 days, liver and kidney tests did not change and no serious adverse effects were reported [12].
Population: Adults in RCTs [11]. 70 healthy adults [12].
Sources: [11], [12]
Caveats: The safety trial's corresponding author is at Akay Natural Ingredients, the maker of the tested oil [12]. Heterogeneity for ALP and BUN was high [11]. In 16 RCTs in type 2 diabetes, AST, ALT and creatinine did not change significantly [7].

Ezetimibe and fenofibrateModerateHow often is not known

Fenofibrate: raised creatinine

Shown to raise serum creatinine about twice as often as placebo across fibrate trials. The label says the rise tends to reverse after stopping.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Increases in serum creatinine were common on fibrates (RR 1.99, 95% CI 1.46 to 2.70) [9]. The fenofibrate label reports creatinine rises that tend to return to baseline after stopping, with unknown clinical significance [7].
Population: Fibrate trials [9]; label statement [7].
Sources: [9], [7]
Caveats: A creatinine rise on fenofibrate may not reflect a fall in kidney filtration, and protein in the urine fell in trials.

NSAIDsModerateHow often is not known

Acute kidney injury

Linked to acute kidney injury about 1.6 to 2 times as often with traditional NSAIDs, including in people with chronic kidney disease.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In cohort studies, risk ratios for acute kidney injury with individual traditional NSAIDs ranged from 1.58 to 2.11 [16]. In the general population, current NSAID use carried an odds ratio of 1.73 (95% CI 1.44 to 2.07), and 1.63 in people with chronic kidney disease [17]. In an 80 km desert race, acute kidney injury occurred in 52% on ibuprofen 400 mg every 4 hours and 34% on placebo (OR 2.1, 95% CI 0.9 to 5.1), one extra case for every 5.5 runners [18]. Renal events were less frequent with celecoxib than ibuprofen in the arthritis trial [11]. In a crossover trial, 600 mg of ibuprofen before 1 hour of running in the heat did not raise kidney or gut injury markers above placebo, though serum IL-8 was higher [19]. Topical diclofenac produced little to no change in creatinine in general populations, with smaller kidney effects than oral diclofenac. In people at raised kidney risk, one cohort found more acute kidney injury in topical NSAID users, mostly of other NSAIDs, and less than with oral NSAIDs [20].
Population: 5 cohort studies [16]; 10 population studies [17]; 89 ultramarathon runners [18]; 11 active adults [19]; 18 studies with more than 500,000 participants [20].
Sources: [16], [17], [18], [11], [19], [20]
Caveats: [16] and [17] are observational. [18] was small and did not reach significance. [19] was small and measured markers, not diagnosed kidney injury. [20] did not pool its studies.

NSAIDsModerateHow often is not known

Use in later pregnancy

The label warns use from about 20 weeks of pregnancy may cause fetal kidney problems, and from 30 weeks early closure of the ductus arteriosus.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The prescription ibuprofen label states that use at about 20 weeks of pregnancy or later may cause fetal kidney problems leading to low amniotic fluid, and that from about 30 weeks NSAIDs raise the risk of premature closure of the fetal ductus arteriosus [12]. In a meta-analysis of observational studies, NSAID use in pregnancy was associated with kidney disease in the child (OR 1.36, 95% CI 1.14 to 1.62), including in the second trimester (OR 1.17) and third trimester (OR 1.10) [21].
Population: Postmarketing reports and studies summarized in the label [12]; 7 studies with 4,159,617 participants [21].
Sources: [12], [21]
Caveats: The label statement is not a trial rate. The authors of [21] state their observational data cannot settle whether the link is causal.

Proton pump inhibitorsModerateHow often is not known

Chronic kidney disease

Linked to about 1.36 times the risk of chronic kidney disease in observational studies, in low-quality evidence. A 3-year randomized trial found no difference from placebo.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Against non-users, proton pump inhibitor users had more acute kidney injury (RR 1.44, 95% CI 1.08 to 1.91), chronic kidney disease (RR 1.36, 95% CI 1.07 to 1.72) and end-stage kidney disease (RR 1.42) [24]. In one community cohort, use was associated with incident chronic kidney disease (adjusted HR 1.50, 95% CI 1.14 to 1.96), including against H2 blocker users (HR 1.39) [25]. In a randomized trial, chronic kidney disease did not differ between pantoprazole and placebo over a median 3 years [19].
Population: 4 cohort and 5 case-control studies with about 2.6 million patients [24]; 10,482 adults in the ARIC cohort with a replication cohort [25]; 17,598 adults in a randomized trial [19].
Sources: [24], [25], [19]
Caveats: The meta-analysis rated the strength of evidence low or insufficient [24]. Observational designs cannot separate the drug from the reasons it was prescribed.

SaltModerateHow often is not known

Hormone and blood fat changes on low-sodium diets

Shown to raise renin, aldosterone, noradrenaline, total cholesterol and triglycerides slightly when sodium was cut sharply in trials. LDL and HDL cholesterol did not change significantly.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: During sodium reduction, renin rose 1.56 ng/mL/hour (82 trials), aldosterone 104 pg/mL (66 trials) and noradrenaline 62.3 pg/mL (35 trials). Total cholesterol rose 5.19 mg/dL (95% CI 2.1 to 8.3, 27 trials) and triglycerides 7.10 mg/dL (95% CI 3.1 to 11.1, 20 trials). LDL cholesterol changed by 2.46 mg/dL (95% CI -1 to 5.9) and HDL by -0.3 mg/dL (95% CI -1.66 to 1.05) [5].
Population: 917 participants for cholesterol, 712 for triglycerides and 2,904 for renin, in randomized trials of low against high sodium diets [5].
Sources: [5]
Caveats: Many trials were short and cut sodium further than guidelines ask. The review authors note these changes were more consistent than the blood pressure effect in people with normal blood pressure [5].

SaltModerateHow often is not known

Higher blood potassium with salt substitutes

Shown to raise blood potassium slightly, by 0.12 mmol/L, in trials that excluded people at risk. Serious high potassium events did not differ from regular salt.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Low-sodium salt substitutes raised blood potassium by 0.12 mmol/L (95% CI 0.07 to 0.18, 6 trials) and made little or no difference to hyperkalemia (4 more per 100,000, 95% CI 47 fewer to 121 more, 5 trials) [7]. In the large trial, serious adverse events attributed to hyperkalemia occurred at 3.35 against 3.30 per 1,000 person-years (rate ratio 1.04, 95% CI 0.80 to 1.37) [10]. A network meta-analysis found no substitute increased adverse events or withdrawals [8].
Population: 784 adults for blood potassium and 22,849 for hyperkalemia [7]. 20,995 older Chinese adults [10]. 34 trials [8].
Sources: [7], [10], [8]
Caveats: Every trial excluded people for whom more potassium is known to be harmful, so these results do not cover them [7]. The network meta-analysis authors limit their safety conclusion to people without kidney impairment [8].

SGLT2 inhibitorsModerateHow often is not known

Early drop in kidney filtration and acute kidney injury

Mixed results: the labels report a small drop in eGFR in the first weeks and kidney injury reports after marketing, while pooled trials found 23% fewer acute kidney injuries.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The empagliflozin label states that starting treatment raises serum creatinine and lowers eGFR within weeks, then stabilizes. In its cardiovascular trial the change generally did not exceed 0.1 mg/dL and 9.0 mL/min/1.73 m² at week 4, and reversed after stopping. Acute kidney injury is listed among postmarketing reports [20]. Across 13 placebo-controlled trials, allocation to an SGLT2 inhibitor lowered the risk of acute kidney injury by 23% (RR 0.77, 95% CI 0.70 to 0.84) [4]. In the dapagliflozin heart failure trial, kidney adverse events did not differ from placebo [2].
Population: Adults in empagliflozin trials [20]; 90,409 participants in 13 trials [4]; 4,744 adults with heart failure [2].
Sources: [20], [4], [2]
Caveats: The label gives no share of people for the early eGFR drop. Postmarketing reports have no denominator.

SpironolactoneModerateHow often is not known

Kidney function and low blood pressure

Shown to raise creatinine in heart failure. The label warns of dehydration, low blood pressure and worsening kidney function from excess fluid loss.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In heart failure with preserved ejection fraction, spironolactone was associated with increased serum creatinine. With frequent monitoring, creatinine of 3.0 mg/dL or higher and dialysis did not differ significantly from placebo [4]. The label states that excessive diuresis may cause symptomatic dehydration, low blood pressure and worsening kidney function, particularly in salt-depleted people or those taking ACE inhibitors or ARBs, and that it can also cause low sodium, low magnesium, low calcium, raised blood sugar and raised uric acid [3].
Population: 3,445 people with heart failure [4].
Sources: [4], [3]
Caveats: The abstract gives no rate for the creatinine rise.

Vitamin DModerateHow often is not known

Hypercalcemia and hypercalciuria

Shown to raise high blood calcium about 54% and high urine calcium about 64% in long-term trials of adults. Kidney stones did not rise.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In 48 studies (19,833 participants) lasting 24 weeks or more, vitamin D raised the risk of hypercalcemia (RR 1.54, 95% CI 1.09 to 2.18, 37 studies) and hypercalciuria (RR 1.64, 95% CI 1.06 to 2.53, 14 studies). Kidney stones did not rise (RR 0.66, 95% CI 0.41 to 1.09, 9 trials). The risk was not modified by dose, duration, baseline level or calcium co-supplementation [54]. In 11 RCTs of 10,000 IU a day or more in people with MS, calcium disturbances were rare and transient [55]. In children up to 5, hypercalcemia did not differ from placebo (RR 0.81, 95% CI 0.53 to 1.24, very low certainty) [15].
Population: Adults in long-term RCTs [54]; adults with MS [55]; pregnant women and young children [15].
Sources: [54], [55], [15]
Caveats: VITAL reported no excess hypercalcemia at 2,000 IU a day [18].

ACE inhibitorsLimitedStudied in pregnancyHow often is not known

Boxed warning: harm to the fetus

FDA states that drugs acting on the renin-angiotensin system can cause injury and death to the developing fetus.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The boxed warning on the lisinopril label states that drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. The label says use in the second and third trimesters reduces fetal kidney function and raises fetal and newborn illness and death, with low amniotic fluid, underdeveloped lungs, skull underdevelopment and kidney failure among the effects described [3]. In a review of published case reports, 52% of 118 newborns exposed to ACE inhibitors before birth had no complications. The others had kidney failure, low amniotic fluid, low blood pressure, growth restriction or death [20]. In a cohort of 29,507 infants, exposure in the first trimester alone was associated with more major congenital malformations than no exposure to blood pressure drugs (RR 2.71, 95% CI 1.72 to 4.27) [21].
Population: 118 published cases of exposure before birth [20]; 209 infants exposed in the first trimester alone among 29,507 infants without maternal diabetes [21].
Sources: [3], [20], [21]
Caveats: Case reports favor poor outcomes and give no rate [20]. The cohort finding is observational, from one US state [21].

ACE inhibitorsLimitedHow often is not known

With NSAIDs

Linked to more acute kidney injury when an NSAID is taken with both a diuretic and an ACE inhibitor or ARB, about 31% higher in one cohort.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Among users of blood pressure drugs, current use of an NSAID with both a diuretic and an ACE inhibitor or ARB was associated with a higher rate of acute kidney injury (rate ratio 1.31, 95% CI 1.12 to 1.53), highest in the first 30 days (1.82, 95% CI 1.35 to 2.46). An NSAID with only one of those drugs was not associated with a higher rate. Acute kidney injury occurred at 7 per 10,000 person-years in the cohort [28]. The lisinopril label states that NSAIDs taken with ACE inhibitors may worsen kidney function in people who are elderly, volume-depleted or have impaired kidneys, and may weaken the blood pressure effect [3].
Population: 487,372 users of blood pressure drugs in UK general practice, mean follow-up 5.9 years [28].
Sources: [28], [3]
Caveats: Observational. The rate is for the whole cohort, not only people on the three-drug combination [28].

ACE inhibitorsLimitedHow often is not known

With lithium

Linked to lithium toxicity, with hospital admission about 7.6 times as likely in the month after an older adult on lithium started an ACE inhibitor.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Among older adults taking lithium, admission for lithium toxicity was more likely within a month of starting an ACE inhibitor (RR 7.6, 95% CI 2.6 to 22.0) [31]. The lisinopril label states that lithium toxicity has been reported with ACE inhibitors and was usually reversible when both drugs were stopped [3].
Population: 10,615 Ontario residents aged 66 and older on lithium, of whom 413 (3.9%) were admitted for lithium toxicity over 10 years [31].
Sources: [31], [3]
Caveats: Observational, with a wide interval. The 3.9% is for all lithium users over 10 years, not for the combination.

AcetaminophenLimitedHow often is not known

Deaths, heart, stomach and kidney events in long-term users

Linked to more deaths, cardiovascular events, gastrointestinal bleeds and kidney function loss at higher doses in cohort studies of regular users.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A systematic review found 8 cohort studies. One of two reporting mortality found the relative rate rose with dose from 0.95 (95% CI 0.92 to 0.98) to 1.63 (1.58 to 1.68). All four reporting cardiovascular events found a dose response, one with risk ratios from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One reported gastrointestinal events or bleeds rising from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Three of four reporting kidney outcomes found a dose response, one with odds of a 30% or greater fall in estimated glomerular filtration rate from 1.40 (0.79 to 2.48) to 2.19 (1.4 to 3.43) [25].
Population: Adults in 8 cohort studies comparing paracetamol use with no use [25].
Sources: [25]
Caveats: Observational. The authors state that channelling bias, where paracetamol is chosen for people already at higher risk, may have had an important impact on the results [25].

AllopurinolLimitedHow often is not known

Kidney injury from xanthine stones

The label warns that allopurinol may cause acute kidney injury through xanthine stones, with higher risk in people who already have kidney disease or stones.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label states that treatment may result in acute kidney injury from xanthine stones, or from urate precipitation in people also taking uricosuric drugs, and that people with chronic kidney disease or a history of kidney stones may be at higher risk [5]. In a trial in chronic kidney disease, kidney function loss did not differ from placebo over 104 weeks [9].
Population: People taking allopurinol, as described in the label [5]; 363 adults with chronic kidney disease [9].
Sources: [5], [9]
Caveats: The label gives no rate.

Alpha-lipoic acidLimitedHow often is not known

Protein in the urine

One trial found protein in the urine more often on 1,200 mg a day than on placebo over 24 months in people with progressive MS.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: On 1,200 mg a day for 24 months, proteinuria was more common than on placebo, and lab monitoring was increased to every 3 months because of it [10].
Population: 115 people with progressive MS [10].
Sources: [10]
Caveats: One trial. The authors describe it as a newly described adverse event [10].

AmitriptylineLimitedHow often is not known

Low sodium

The label reports low blood sodium on amitriptyline, often from inappropriate antidiuretic hormone release, with older adults and people on diuretics at greater risk. It gives no rate.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Hyponatremia has occurred, in many cases from the syndrome of inappropriate antidiuretic hormone secretion, with headache, confusion and unsteadiness, and in severe cases seizures, coma and death. Older adults, people taking diuretics and people who are volume depleted may be at greater risk [13].
Population: Reports summarized in the label [13].
Sources: [13]
Caveats: No rate or measured sodium change is given.

Antiplatelets: clopidogrel and low-dose aspirinLimitedHow often is not known

Kidney function and blood pressure medicines with aspirin

The aspirin label warns that NSAIDs including aspirin taken with ACE inhibitors or similar drugs may worsen kidney function in older or dehydrated people.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The prescription aspirin label states that in people who are elderly, volume-depleted, including those on diuretics, or who have compromised kidney function, NSAIDs including aspirin taken with renin-angiotensin system inhibitors may result in deterioration of kidney function, including possible acute kidney failure, usually reversible. It also states that NSAIDs may weaken the blood pressure lowering effect of these drugs [23].
Population: A class statement in labeling, with no study counts [23].
Sources: [23]
Caveats: The label gives no rate and does not separate low-dose aspirin from other NSAIDs.

ARBs (angiotensin receptor blockers)LimitedHow often is not known

Boxed warning: harm to the fetus

FDA states that drugs acting on the renin-angiotensin system can cause injury and death to the developing fetus.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The losartan label states that use of drugs acting on the renin-angiotensin system in the second and third trimesters reduces fetal kidney function and raises fetal and newborn illness and death, with low amniotic fluid, underdeveloped lungs, skull underdevelopment and kidney failure among the effects described [10]. In a review of published case reports, 13% of 68 newborns exposed to ARBs before birth had no complications, against 52% of those exposed to ACE inhibitors. Complications included kidney failure, low amniotic fluid, death, low blood pressure and growth restriction [23].
Population: 68 published cases of exposure to ARBs before birth, in 35 reports [23].
Sources: [10], [23]
Caveats: Case reports favor poor outcomes and give no rate [23].

ARBs (angiotensin receptor blockers)LimitedHow often is not known

With lithium

The label warns that raised lithium levels and lithium toxicity have been reported when lithium is taken with an ARB. It gives no rate.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The losartan label states that increases in serum lithium concentrations and lithium toxicity have been reported during use of lithium with angiotensin II receptor antagonists [10].
Population: People taking lithium with an ARB, as described in the label [10].
Sources: [10]
Caveats: Based on reports, with no rate or comparison group.

B-complex vitaminsLimitedHow often is not known

Faster kidney decline and more vascular events in diabetic kidney disease

One trial found kidney filtration fell faster on B vitamins than placebo in 238 people with diabetic nephropathy, and vascular events or death were twice as common.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: At 36 months, kidney filtration fell 16.5 mL/min/1.73 m² on B vitamins and 10.7 on placebo (difference -5.8, 95% CI -10.6 to -1.1). Heart attack, stroke, revascularization or death was twice as common (HR 2.0, 95% CI 1.0 to 4.0) [6].
Population: 238 people with type 1 or 2 diabetes and diabetic nephropathy at 5 Canadian centers [6].
Sources: [6]
Caveats: One trial. Dialysis need did not differ (HR 1.1) [6].

Black seed oilLimitedHow often is not known

Kidney injury and muscle breakdown

Case reports: one person had acute kidney injury, muscle breakdown and liver toxicity after drinking black seed oil.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A 2024 case report describes acute kidney injury, rhabdomyolysis and liver toxicity after a person drank black seed oil [14].
Population: One case [14].
Sources: [14]
Caveats: A single case report cannot give a rate.

CalciumLimitedHow often is not known

Kidney stones

One trial found kidney stones about 17% more common on calcium plus vitamin D than placebo over 7 years in postmenopausal women.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Kidney stones were more common on calcium plus vitamin D than placebo (HR 1.17, 95% CI 1.02 to 1.34) over an average 7.0 years [7].
Population: 36,282 postmenopausal women in the Women's Health Initiative [7].
Sources: [7]
Caveats: One trial, of calcium combined with vitamin D.
Why limited: This rests on one trial, of 36,282 people. Strength counts independent studies that agree, so one trial is limited at any size.

ChromiumLimitedHow often is not known

Kidney and liver failure

Case reports: a woman taking 1,200 to 2,400 µg a day for months developed anemia, liver injury and kidney failure needing dialysis, and recovered.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A 33-year-old woman taking 1,200 to 2,400 µg a day of chromium picolinate for 4 to 5 months for weight loss developed anemia, liver injury with enzymes 15 to 20 times normal, and kidney failure needing dialysis. She recovered within a year [13].
Population: One case report [13].
Sources: [13]
Caveats: A single case. Plasma chromium was 2 to 3 times normal [13].

Direct oral anticoagulants (DOACs)LimitedHow often is not known

FDA boxed warning on edoxaban: less protection with high kidney clearance

FDA states that people with atrial fibrillation and creatinine clearance above 95 mL/min had more ischemic strokes on edoxaban 60 mg than on warfarin.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In the pivotal edoxaban trial, the rate of ischemic stroke in people with creatinine clearance above 95 mL/min was higher on edoxaban 60 mg than on warfarin (HR 2.16, 95% CI 1.17 to 3.97). In people with clearance above 50 and up to 80 mL/min the rate was lower on edoxaban (HR 0.63, 95% CI 0.44 to 0.89). The label states that people with high clearance had lower edoxaban blood levels [21].
Population: Subgroups by kidney function within a trial of 21,105 patients [21][6].
Sources: [21], [6]
Caveats: A subgroup finding from one trial. The evidence is for edoxaban.

Direct oral anticoagulants (DOACs)LimitedHow often is not known

Medicines that raise or lower DOAC blood levels

The labels warn that ketoconazole, itraconazole and ritonavir raise blood levels of these drugs, and that rifampin, carbamazepine, phenytoin and St. John's wort lower them.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The apixaban label states that combined P-glycoprotein and strong CYP3A4 inhibitors such as ketoconazole, itraconazole and ritonavir increase apixaban blood levels, and that combined inducers reduce them [22]. The rivaroxaban label advises against use with ketoconazole and ritonavir, and with inducers such as carbamazepine, phenytoin, the antibiotic rifampin and St. John's wort [23]. The dabigatran label states that rifampin reduces dabigatran exposure, and that dronedarone or systemic ketoconazole with moderate kidney impairment raises exposure to the level seen in severe kidney impairment [20].
Population: Interaction studies summarized in labeling [22][23][20].
Sources: [22], [23], [20]
Caveats: Changes in blood levels, with no rate of bleeding or clots given.

Direct oral anticoagulants (DOACs)LimitedHow often is not known

Reduced kidney function

The labels state that reduced kidney function raises blood levels of dabigatran and edoxaban. They give no bleeding rate for this.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The dabigatran label states that P-glycoprotein inhibition and impaired renal function are the major independent factors that increase exposure to dabigatran, and that it cannot give dosing for creatinine clearance of 30 mL/min or below in some uses [20]. The edoxaban label states that the kidneys account for about 50% of edoxaban clearance, and that blood levels are higher with poor kidney function [21].
Population: Pharmacokinetic data summarized in labeling [20][21].
Sources: [20], [21]
Caveats: A change in drug exposure, with no rate of harm given.

DulaglutideLimitedHow often is not known

Kidney injury from dehydration

The label reports acute kidney injury, some needing dialysis, mostly in people dehydrated by nausea, vomiting or diarrhea. It gives no rate.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Postmarketing reports describe acute kidney injury, in some cases needing hemodialysis, in people on GLP-1 receptor agonists including dulaglutide, most after gastrointestinal reactions led to dehydration [1].
Population: Postmarketing reports [1].
Sources: [1]
Caveats: Reports, with no denominator.

GlutamineLimitedHow often is not known

Kidney markers

One small trial found estimated GFR fell 13.3% on high-dose glutamine against 2.9% on control over 14 days in older adults.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In a crossover RCT of 30 adults (mean age 69) given 0.5 g per kg a day for 14 days, estimated GFR fell 13.3% on glutamine against 2.9% on a casein control, with small rises in urea nitrogen and creatinine; no adverse clinical effects were seen [7]. A review of kidney safety in athletes found 5 glutamine studies; short-term (20 to 30 g within a few hours) and 2-week (0.1 g per kg four times a day) use showed no significant adverse effects in healthy athletes, while the review notes glomerulosclerosis and raised creatinine reported in the setting of diabetic kidney disease [8].
Population: Older care-home residents [7]; athletes and bodybuilders [8].
Sources: [7], [8]
Caveats: The authors of [7] describe the eGFR drop as below their 25% threshold for biological significance. Reference [8] is a narrative review of few studies.

H2 blockersLimitedHow often is not known

Confusion and other brain effects in older or kidney-impaired people

The labels warn of confusion, delirium, hallucinations and seizures reported in older people and people with reduced kidney function on famotidine, and in severely ill people on cimetidine.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The famotidine label reports confusion, delirium, hallucinations, disorientation, agitation, seizures and lethargy in elderly patients and those with moderate or severe kidney impairment, in whom blood levels are higher [2]. The cimetidine label reports reversible confusional states, mostly in severely ill patients, usually starting within 2 to 3 days and clearing within 3 to 4 days of stopping [14].
Population: Reports summarized in labeling [2][14].
Sources: [2], [14]
Caveats: Reports with no denominator.

H2 blockersLimitedHow often is not known

QT prolongation with kidney impairment

The famotidine label reports prolonged QT intervals in people with moderate or severe kidney impairment, in whom famotidine is cleared more slowly. It gives no rate.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label states that CNS adverse reactions and prolonged QT intervals have been reported in patients with moderate and severe renal impairment, and lists a lower dose when creatinine clearance is under 60 mL/minute [2].
Population: Reports summarized in labeling [2].
Sources: [2]
Caveats: No rate or trial data are given.

High-protein dietLimitedHow often is not known

Kidney function in people with kidney disease

Mixed results: two trials including people with early kidney disease found no harm to kidney function, while a cohort linked more protein to faster decline in women with mild impairment.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In type 2 diabetes with early kidney disease, 12 months on a moderate-protein against a standard-protein weight-loss diet did not change isotope-measured GFR, eGFR, cystatin C or albuminuria. Weight loss improved kidney function on both [10]. In a 2-year trial, eGFR rose similarly on low-carbohydrate (protein 22% of energy), Mediterranean and low-fat diets, and rose 7.1% in people starting with eGFR under 60 [14]. Over 11 years, each 10 g a day more protein was linked to an eGFR change of -1.69 mL/min/1.73 m² (95% CI -2.93 to -0.45) in women with mild renal insufficiency, and to no change in women with normal function [15].
Population: 76 adults with type 2 diabetes and an albumin to creatinine ratio of 3 to 30 mg/mmol, 45 completing [10]; 318 adults with eGFR of 30 or more, 86% men [14]; 1,624 women aged 42 to 68 in the Nurses' Health Study, observational [15].
Sources: [10], [14], [15]
Caveats: The trials were small or not designed around kidney disease, and the protein difference was modest, 19 g a day in [10]. The cohort used food questionnaires, and the link was strongest for nondairy animal protein [15].

Hormonal birth controlLimitedHow often is not known

High potassium with drospirenone

The label warns drospirenone can raise potassium, comparable to spironolactone 25 mg, and contraindicates it in kidney, liver or adrenal conditions that raise potassium.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Drospirenone 3 mg has anti-mineralocorticoid activity comparable to spironolactone 25 mg, with potential for high potassium in high-risk patients. The label advises checking potassium in the first cycle for women on other long-term drugs that raise potassium [2].
Population: Label statement [2].
Sources: [2]
Caveats: No rate given.

IV vitamin therapyLimitedHow often is not known

Kidney injury from high-dose vitamin C

Case reports: kidney failure attributed to oxalate after IV vitamin C, mostly in people with cancer, sepsis, burns or existing kidney disease.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A scoping review found 24 case reports of kidney failure presumed to be oxalate nephropathy after IV vitamin C. They occurred in people with cancer, sepsis or burns or other confounding conditions, and in most the kidney failure could be attributed to the illness or its treatment. Existing kidney dysfunction was a key risk factor for impaired clearance of large doses [12]. A systematic review lists oxalate nephropathy among the major risks of high-dose IV vitamin C, especially with very large or repeated doses [9].
Population: 24 case reports [12]. A systematic review of studies from 2010 to 2025 [9].
Sources: [12], [9]
Caveats: Case reports give no rate, and most patients were seriously ill for other reasons [12].

LiraglutideLimitedHow often is not known

Acute kidney injury from dehydration (label warning)

The label reports cases of acute kidney injury, some needing dialysis, mostly in people dehydrated by nausea, vomiting or diarrhea.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label reports postmarketing cases of acute kidney injury, some requiring hemodialysis, in people treated with liraglutide. Most occurred in people whose nausea, vomiting or diarrhea led to dehydration. The label tells prescribers to monitor kidney function in people reporting those reactions, especially when starting and raising the dose [13].
Population: Postmarketing reports summarized in the label [13].
Sources: [13]
Caveats: These are reports, not rates from a controlled comparison.

Loop diureticsLimitedHow often is not known

FDA boxed warning: profound fluid and electrolyte loss

The furosemide and bumetanide labels warn these potent diuretics, in excessive amounts, can cause profound loss of water and electrolytes, so dosing needs medical supervision.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Both labels carry a boxed warning that the drug is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion, and that dose and schedule must be adjusted to the individual [10][15]. The furosemide label adds that excessive diuresis may cause dehydration, low blood volume, circulatory collapse and possibly blood clots, particularly in older people [10].
Population: Label statements [10][15].
Sources: [10], [15]
Caveats: The labels give no rate.

Loop diureticsLimitedHow often is not known

Drug interactions

The labels warn of more hearing damage with aminoglycoside antibiotics, lithium toxicity, weaker effect with indomethacin, and low blood pressure and kidney decline with ACE inhibitors or ARBs.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Furosemide may raise the ear toxicity of aminoglycoside antibiotics, and the combination is to be avoided except in life-threatening situations. Diuretics reduce lithium clearance, with a high risk of lithium toxicity. Indomethacin may reduce furosemide's effect on sodium and blood pressure, and aspirin temporarily reduced kidney clearance in one small study. With ACE inhibitors or ARBs, furosemide may lead to severe low blood pressure and worse kidney function. Sucralfate may reduce its effect [10]. The torsemide label reports ear toxicity with gentamicin [1].
Population: Label statements and case reports [10][1].
Sources: [10], [1]
Caveats: Label warnings, mostly without measured rates.

MultivitaminLimitedHow often is not known

Single-nutrient harms

Limited evidence: single supplements were linked to hip fracture with vitamin A, hemorrhagic stroke with vitamin E, and kidney stones with vitamin C and calcium.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The Task Force review found limited evidence linking some single supplements to serious harms: hip fracture with vitamin A, hemorrhagic stroke with vitamin E, and kidney stones with vitamin C and calcium [4].
Population: Healthy adults in RCTs and cohorts [4].
Sources: [4]
Caveats: These are single-nutrient findings, not tests of multivitamins.

OrlistatLimitedHow often is not known

Kidney injury from oxalate

The label warns of oxalate kidney stones and oxalate kidney damage with renal failure. One case report describes injury that improved after stopping.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The Xenical label warns of oxalate kidney stones and oxalate nephropathy with renal failure [9]. A case report describes acute kidney injury with calcium oxalate crystals on biopsy in a woman with chronic kidney disease after an orlistat dose increase, improving after it was stopped [13].
Population: Postmarketing reports [9]; one patient [13].
Sources: [9], [13]
Caveats: No trial measured this as an outcome.

PotassiumLimitedHow often is not known

Hyperkalemia with kidney disease and potassium-sparing drugs

Case reports: life-threatening high potassium occurred with kidney disease or potassium-sparing drugs. A small trial found larger potassium rises in chronic kidney disease.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In a crossover trial, a single 40 mmol oral dose of potassium chloride or potassium citrate raised plasma potassium more in 9 patients with stage 3b to 4 chronic kidney disease than in 18 healthy adults, and did not raise sodium excretion in the patients [15]. An 88-year-old man with chronic kidney disease reached a potassium of 7.5 mEq/L after eating a potassium-enriched salt substitute his family brought to the hospital [16]. Two patients after cardiac surgery with normal kidney function developed life-threatening hyperkalemia while taking an ACE inhibitor, a potassium-sparing diuretic and a high-potassium diet [17].
Population: 27 adults in a placebo-controlled crossover trial [15]. Case reports, 3 patients [16][17].
Sources: [15], [16], [17]
Caveats: The trial measured 4 hours after one dose [15]. Case reports show that the event can happen, not how often.

Proton pump inhibitorsLimitedHow often is not known

Acute interstitial nephritis

The label warns that acute tubulointerstitial nephritis, a kidney inflammation, has occurred with proton pump inhibitors at any point during use. It gives no rate.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label describes acute tubulointerstitial nephritis from reported case series, presenting with allergic-type symptoms or with nonspecific signs of reduced kidney function such as malaise and nausea [3]. A meta-analysis of observational studies found an association with acute interstitial nephritis (RR 3.61, 95% CI 2.37 to 5.51), rated insufficient strength of evidence [24].
Population: Case series summarized in labeling [3]; observational studies [24].
Sources: [3], [24]
Caveats: No denominator in the case series. The pooled estimate rests on observational data rated insufficient [24].

SemaglutideLimitedHow often is not known

Acute kidney injury from dehydration (label warning)

The label reports acute kidney injury, some needing dialysis, mostly in people dehydrated from nausea, vomiting or diarrhea, and tells prescribers to monitor kidney function.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label reports postmarketing cases of acute kidney injury, some requiring hemodialysis, in people treated with semaglutide. Most occurred in people whose nausea, vomiting or diarrhea led to dehydration. The label tells prescribers to monitor kidney function in people reporting those reactions, especially when starting and raising the dose [14].
Population: Postmarketing reports summarized in the label [14].
Sources: [14]
Caveats: These are reports, not rates from a controlled comparison.

SpironolactoneLimitedHow often is not known

With potassium supplements, NSAIDs or heparin

The label warns that potassium supplements, potassium salt substitutes, NSAIDs and heparin can raise potassium further, and that NSAIDs can blunt the diuretic effect.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label states that taking spironolactone with potassium supplements or drugs that can increase potassium may lead to severe hyperkalemia, and names NSAIDs, heparin and low molecular weight heparin among those drugs. It states that NSAIDs can reduce the diuretic and blood pressure effect, and that kidney function can worsen with nephrotoxic drugs such as NSAIDs [3].
Population: People taking spironolactone with these products, as described in the label [3].
Sources: [3]
Caveats: The label gives no rate.

SpironolactoneLimitedHow often is not known

With lithium or digoxin

The label warns that spironolactone lowers the kidney's clearance of lithium, raising the risk of lithium toxicity, and interferes with some digoxin blood tests.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label states that spironolactone, like other diuretics, reduces the renal clearance of lithium and so increases the risk of lithium toxicity. It also states that spironolactone and its metabolites interfere with radioimmunoassays for digoxin and raise the apparent digoxin level, and that the effect on actual digoxin exposure is unknown [3].
Population: People taking spironolactone with lithium or digoxin, as described in the label [3].
Sources: [3]
Caveats: The label gives no rate.

Testosterone therapyLimitedStudied in menHow often is not known

Acute kidney injury and pulmonary embolism

One trial found more acute kidney injury and blood clots in the lungs on testosterone in men at high heart risk. Event counts were not given.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: TRAVERSE reported a higher incidence of acute kidney injury and pulmonary embolism in the testosterone group than the placebo group [8].
Population: 5,246 men aged 45 to 80 at high cardiovascular risk [8].
Sources: [8]
Caveats: One trial. The abstract reports these as observed differences without event counts.
Why limited: This rests on one trial, of 5,246 people. Strength counts independent studies that agree, so one trial is limited at any size.

Testosterone therapyLimitedHow often is not known

Complications after knee replacement

Linked to more kidney injury, implant infection, revision surgery and fracture after knee replacement in people using testosterone.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In people having a total knee replacement, testosterone use was linked to more acute kidney injury within 3 months (OR 1.3, 95% CI 1.1 to 1.6), joint infection around the implant (OR 1.8, 95% CI 1.3 to 2.7), revision surgery (OR 1.3, 95% CI 1.2 to 1.5) and fracture around the implant (OR 2.0, 95% CI 1.1 to 3.7). Pulmonary embolism (OR 1.2, 95% CI 0.9 to 1.6) and deep vein thrombosis (OR 1.1, 95% CI 0.8 to 1.4) did not differ [18].
Population: 4 retrospective matched cohort studies [18].
Sources: [18]
Caveats: Observational studies only. They show association, not cause [18].

Thiazide diureticsLimitedHow often is not known

Kidney function changes

Limited evidence: creatinine rises were more frequent on thiazides than placebo in two trials, and kidney injury was more frequent on chlorthalidone than hydrochlorothiazide in one cohort.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A creatinine level above 150% of baseline was more frequent on hydrochlorothiazide than placebo in the kidney stone trial [13], and reversible creatinine rises were more frequent on chlorthalidone than placebo in advanced kidney disease [3]. In a cohort of first-time users, acute kidney failure (HR 1.37, 95% CI 1.15 to 1.63) and chronic kidney disease (HR 1.24, 95% CI 1.09 to 1.42) were more frequent on chlorthalidone than hydrochlorothiazide [8].
Population: 416 people with recurrent kidney stones [13]; 160 people with stage 4 chronic kidney disease [3]; 730,225 first-time users [8].
Sources: [13], [3], [8]
Caveats: None of the abstracts gives the rates.

Thiazide diureticsLimitedHow often is not known

With lithium

Mixed results: the label warns that diuretics reduce lithium clearance and raise toxicity risk, and one cohort did not find more toxicity admissions with thiazides.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The hydrochlorothiazide label states that diuretics reduce the kidney's clearance of lithium and add a high risk of lithium toxicity [14]. In a study of older adults on lithium, thiazide diuretics were not independently associated with a significant rise in hospital admission for lithium toxicity, while loop diuretics (RR 5.5) and ACE inhibitors (RR 7.6) were [25].
Population: 10,615 Ontario residents aged 66 and older on lithium [25].
Sources: [14], [25]
Caveats: One observational study, in older adults, counting only hospital admissions.

TirzepatideLimitedHow often is not known

Acute kidney injury from dehydration (label warning)

The label reports acute kidney injury, some needing dialysis, mostly in people dehydrated from nausea, vomiting or diarrhea, and tells prescribers to monitor kidney function.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label reports postmarketing cases of acute kidney injury, some requiring hemodialysis, in people treated with GLP-1 receptor agonists or Zepbound. Most occurred in people whose nausea, vomiting or diarrhea led to dehydration. The label tells prescribers to monitor kidney function in people reporting those reactions, especially when starting and raising the dose [25].
Population: Postmarketing reports summarized in the label [25].
Sources: [25]
Caveats: These are reports, not rates from a controlled comparison.

TopiramateLimitedHow often is not known

The label reports that phenytoin and carbamazepine lower topiramate levels, while topiramate can raise lithium and amitriptyline levels, and other carbonic anhydrase inhibitors add to acidosis and stones.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Phenytoin and carbamazepine significantly lowered topiramate concentrations. Hydrochlorothiazide raised topiramate exposure. Topiramate lowered pioglitazone exposure, raised lithium exposure at doses up to 600 mg a day, and produced large increases in amitriptyline concentration in some people. Zonisamide, acetazolamide and other carbonic anhydrase inhibitors may worsen metabolic acidosis and raise kidney stone risk [3].
Population: Drug interaction studies described in the label [3].
Sources: [3]
Caveats: Changes in blood levels, with no rate of harm given.

TribulusLimitedHow often is not known

Kidney and liver injury

Case reports: three men developed serious liver or kidney injury after taking tribulus. Case reports cannot give a rate or prove cause.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A young man drinking a tribulus water preparation for 2 days to prevent kidney stones developed seizure, very high aminotransferases and raised creatinine, which normalized after stopping [11]. A young healthy man developed severe hyperbilirubinemia followed by acute kidney failure with bile casts in the kidney tubules [12]. A 46-year-old man taking tribulus daily for 2 months had bilirubin peak at 48 mg/dL and creatinine at 7.1, with a liver biopsy consistent with drug-induced injury. He was treated with plasmapheresis and recovered [13].
Population: Three case reports [11][12][13].
Sources: [11], [12], [13]
Caveats: Case reports cannot give a rate or prove cause.

TurmericLimitedHow often is not known

Kidney toxicity with immunosuppressive drugs

Limited evidence: a review reported kidney toxicity from high-dose turmeric taken with immunosuppressive drugs. Case numbers and drugs were not given.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A systematic review of 21 studies in people on dialysis or immunosuppressive drugs reported a food-drug interaction in which high doses of turmeric taken with immunosuppressive drugs caused kidney toxicity [50].
Population: RCTs and case reports in dialysis patients and immunosuppressed patients [50].
Sources: [50]
Caveats: The abstract does not give the number of cases or the drugs involved [50].

Vitamin B12LimitedHow often is not known

Faster kidney decline in diabetic nephropathy

One trial found faster kidney decline and more heart events on high-dose B vitamins in people with diabetic kidney disease. The tablet combined folic acid and B6.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: At 36 months, filtration rate fell 16.5 mL/min/1.73 m² on high-dose B vitamins and 10.7 on placebo, a difference of -5.8 (95% CI -10.6 to -1.1). A composite of heart attack, stroke, revascularization and death occurred more often on B vitamins (HR 2.0, 95% CI 1.0 to 4.0). Dialysis did not differ [13].
Population: 238 people with type 1 or 2 diabetes and diabetic nephropathy, mean follow-up 31.9 months [13].
Sources: [13]
Caveats: One trial of a combined tablet with folic acid and B6, so the effect cannot be assigned to B12 alone.

Vitamin CLimitedHow often is not known

Kidney stones in men

Linked to about 43% more kidney stones in men with intake of 1,000 mg a day or more. No link appeared in women.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In men, total vitamin C intake of 1,000 mg a day or more was associated with more kidney stones than intake under 90 mg (HR 1.43, 95% CI 1.15 to 1.79). Supplements of 1,000 mg or more were associated with an HR of 1.19 (95% CI 1.01 to 1.40). No association appeared in women, or for vitamin C from food [21].
Population: 156,735 women and 40,536 men in US cohorts, median follow-up 11.3 to 11.7 years, 6,245 stones [21].
Sources: [21], [22]
Caveats: Observational, intake from food questionnaires, and stone type was not known for every case [21]. A 2026 meta-analysis of 9 interventional studies found that vitamin C supplements raised 24-hour urinary oxalate by 6.45 mg against placebo, in people with and without past stones. Urinary citrate and calcium did not change. Urinary oxalate is a stone risk factor, not a count of stones [22].

WarfarinLimitedHow often is not known

Calciphylaxis and cholesterol microemboli

The label warns of fatal and serious calciphylaxis, and of cholesterol microemboli that can cause purple toes syndrome. It gives no rate.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label states that warfarin can cause fatal and serious calciphylaxis in people with and without end-stage kidney disease. It states that anticoagulation may enhance the release of atheromatous plaque emboli, most often to the kidneys, and describes microemboli to the feet as purple toes syndrome, with some cases progressing to necrosis or death [11].
Population: Reports summarized in labeling [11].
Sources: [11]
Caveats: No denominator is given.

WarfarinLimitedHow often is not known

Kidney injury

The label warns that acute kidney injury may occur in people with kidney disease, possibly related to episodes of excessive anticoagulation and blood in the urine.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label states that in people with altered glomerular integrity or a history of kidney disease, acute kidney injury may occur with warfarin, possibly in relation to episodes of excessive anticoagulation and hematuria [11].
Population: A warning in labeling, with no study counts [11].
Sources: [11]
Caveats: The label gives no rate.

Thunder god vineCautionStrong

Side effects across studies

Adverse events occurred in about 27% to 31% of users across hundreds of studies, most often digestive, reproductive and skin effects, with 4.7% severe.

The numbers and sources

Effect: Across 594 studies of 23,256 TwHF users, 26.7% had adverse events (95% CI 24.8% to 28.8%). Digestive symptoms occurred in 13.3%, reproductive adverse outcomes in 11.7%, skin reactions in 7.8%, blood count events in 6.5% and cardiovascular events in 4.9% [11]. Across 46 studies (2,437 people on Tripterygium wilfordii polyglycoside), 30.75% had adverse events and 4.68% had severe events. The authors list intestinal, reproductive, liver, kidney, blood and skin toxicity, related to dose, course and combined drugs [12].
Population: Users in trials and observational studies [11]. Users in RCTs, controlled trials and single-arm trials [12].
Sources: [11], [12]
Caveats: Rates varied widely by study type [11]. Heterogeneity was high (I² 97%) [12].

Horse chestnutLimited

Kidney failure after intravenous aescin

Case reports: one heart surgery center linked acute kidney failure, mostly in young children, to intravenous aescin. Oral extract was not involved.

The numbers and sources

Effect: One heart surgery center linked a rise in acute kidney failure after cardiac surgery, mostly in children aged 2 to 10, to intravenous aescin. 39% of affected patients needed peritoneal dialysis and overall mortality was 10.7%. No similar case occurred in almost a year after the drug was dropped [10].
Population: Patients after heart surgery at one center [10].
Sources: [10]
Caveats: This concerns intravenous aescin, not oral extract. The abstract does not give the number of cases.

Juice cleanseLimited

Oxalate kidney injury

Case reports: oxalate-rich juice cleanses and juicing were followed by acute kidney injury from oxalate crystals, with several people left on dialysis.

The numbers and sources

Effect: A patient with chronic kidney disease developed oxalate-induced acute renal failure after oxalate-rich juices, one of 3 presumed diet-induced cases among 65 Mayo Clinic patients with biopsy-proven renal oxalate crystals [4]. A 65-year-old woman with normal kidney function developed acute oxalate nephropathy after a green smoothie cleanse and progressed to end-stage kidney disease [5]. A 68-year-old man on a daily spinach-heavy juice, about 10 times typical oxalate intake, developed end-stage kidney disease and remained on dialysis a year later [6]. A man with diabetes and normal kidney function needed dialysis after a one-week juice diet [7].
Population: Case reports and a single-center case review [4][5][6][7].
Sources: [4], [5], [6], [7]
Caveats: Case reports cannot give a rate. Several patients had predisposing factors: chronic kidney disease [4], past gastric bypass and recent prolonged antibiotics [5], volume depletion [6], or age and diabetes [7]. The one-week juice diet in [7] followed a gastrointestinal bleed, not a cleanse.

Mixed results14

Cystatin CModerate

Factors other than kidney function that shift the result

Mixed results: cystatin C did not vary with muscle mass as creatinine did, yet differed by sex, age, diabetes, inflammation and thyroid state at the same kidney function.

The numbers and sources

Compared with: Measured glomerular filtration rate, or creatinine in the same people
Effect: In 170 healthy adults, lean mass was significantly related to serum and urinary creatinine and not to cystatin C, and cystatin C did not differ between sedentary people and those with moderate or intense physical activity [19]. In 3,418 patients with measured GFR, after adjustment for GFR, cystatin C was 4.3% lower for every 20 years of age and 9.2% lower in women. Diabetes went with 8.5% higher cystatin C, and higher C-reactive protein, higher white cell count and lower albumin went with higher cystatin C [15]. In 22 patients treated for thyroid disease, cystatin C rose from 0.84 to 1.1 mg/L as hypothyroidism was corrected and fell from 1.32 to 0.95 mg/L as hyperthyroidism was corrected, the opposite direction to creatinine [20]. A kidney guideline lists smoking and steroid use among the conditions that affect cystatin C apart from kidney function [2].
Population: 170 healthy adults, 92 women and 78 men [19]. 3,418 people from clinical trials and a clinical population with chronic kidney disease [15]. 9 patients with hypothyroidism and 13 with hyperthyroidism [20].
Sources: [19], [15], [20], [2]
Caveats: The sources state no threshold for agreement. The thyroid finding comes from a case series of 22 patients [20].

Cystatin CModerate

Agreement between laboratories and assays

Mixed results: US laboratories differed by 14% on the same sample in 2014 and by about 10% in 2019, after makers recalibrated their methods.

The numbers and sources

Compared with: A target value traceable to the international reference material ERM-DA471/IFCC
Effect: In a 2014 US proficiency survey of 123 laboratories, a serum pool from healthy donors with a target of 0.960 mg/L was reported at a mean of 0.894 mg/L with a coefficient of variation of 14.3%. Mean results by reagent maker ranged from 0.780 to 1.061 mg/L, and the authors called the method-specific biases substantial [7]. In the 2019 survey, a healthy-donor pool with a target of 0.725 mg/L was reported at a mean of 0.731 mg/L with a coefficient of variation of 9.7%, and a pool from people with chronic kidney disease with a target of 2.136 mg/L at 2.155 mg/L (8.4%), which the authors called a marked improvement [21]. The international reference material was certified in 2010 [6].
Population: 123 laboratories in the 2014 survey [7]. Laboratories taking part in the 2019 survey [21].
Sources: [7], [21], [6]
Caveats: A result near a cut point may be classified differently by another laboratory. Reference intervals and cut points published before the methods were recalibrated may not fit current results.

Estimated GFR (eGFR)Moderate

Variation from one test to the next

Shown to vary about 5% within a person between tests. KDIGO treats a change of more than 20% as beyond expected variability.

The numbers and sources

Compared with: Repeat measurements in the same person
Effect: KDIGO reports within-person biological variation of 5.3% (95% CI 4.5 to 6.4) for creatinine-based eGFR, and reference change values of 14% to 20% in people with chronic kidney disease, meaning a change smaller than that can arise from normal biological and analytical variation. Its practice point is that a change in eGFR of more than 20% on a later test exceeds the expected variability [3]. In 91 healthy Europeans sampled weekly for 10 weeks, within-person variation of serum creatinine was 4.4% (95% CI 4.2 to 4.7) with an enzymatic assay and 4.7% with an alkaline picrate assay. Analytical variation was 1.1% for the enzymatic method and 4.4% for the alkaline picrate method, which failed the imprecision specification the authors derived [18].
Population: 91 healthy adults aged 21 to 69 at 6 European laboratories [18]. KDIGO draws its figures from earlier studies of people with and without chronic kidney disease [3].
Sources: [3], [18]
Caveats: The KDIGO figures are quoted from the guideline, not from the primary studies. A laboratory report does not always say which creatinine method was used.

Loop diureticsModerate

Preventing or treating acute kidney injury

Mixed results: furosemide did not change deaths or dialysis in kidney injury, while a Cochrane review found less new injury when diuretics were given beforehand.

Compared with placebo or usual care [11]; placebo, no treatment or intravenous fluids [12]

The numbers and sources

Effect: In adults with or at risk of acute kidney failure, furosemide did not change in-hospital mortality (RR 1.11, 95% CI 0.92 to 1.33), need for dialysis (RR 0.99, 95% CI 0.80 to 1.22) or persistent low urine output [11]. For treating established injury, diuretics made little or no difference to dialysis (RR 0.93) or death (RR 1.08) and raised hypotension and arrhythmias. For prevention, diuretics lowered new kidney injury (RR 0.75, 95% CI 0.61 to 0.92, low certainty), dialysis (RR 0.63) and death (RR 0.73) [12].
Population: 849 patients in 9 furosemide trials [11]; 9,871 people in 64 studies, 8,078 in prevention studies [12].
Sources: [11], [12]
Caveats: [12] pooled diuretics as a group, not loop diuretics alone, and the prevention finding had high heterogeneity (I² 77%).

Methylmalonic acid (MMA)Moderate

Reduced kidney function

Linked to levels about 50% to 70% higher in US adults with impaired kidney function than in those with normal function.

The numbers and sources

Compared with: Adults with normal kidney function in the same survey
Effect: In the US national survey, impaired kidney function went with methylmalonic acid about 50% to 70% higher in both survey periods. Geometric means were 140 and 145 nmol/L with normal function and 235 and 249 with chronic kidney disease stages 3 to 5. Serum B12 showed little change [5]. In a Norwegian population, age, plasma creatinine, B12 and sex were the strongest determinants and together accounted for 16% of the variation [6].
Population: 10,020 US adults aged 20 and older, surveyed from 2011 to 2014 [5]. 6,946 Norwegian adults aged 47 to 49 or 71 to 74 [6].
Sources: [5], [6]
Caveats: Cross-sectional. The surveys state no threshold for agreement, so the result is given as numbers only. A raised level in a person with reduced kidney function may not reflect B12 status [5].

Serum creatinineModerate

Variation from one draw to the next in one person

Shown to vary about 4.4% from one draw to the next within the same person, in a 10-week European study and a pooled estimate.

The numbers and sources

Compared with: The same person's results on repeated draws
Effect: In 91 healthy Europeans sampled weekly for 10 weeks, within-person variation of serum creatinine was 4.4% (95% CI 4.2 to 4.7) with an enzymatic assay and 4.7% (4.4 to 4.9) with an alkaline picrate assay, with no difference between men and women [16]. The European Federation of Clinical Chemistry and Laboratory Medicine database gives a pooled within-person variation of 4.4%, with lower and upper limits of 2.3% and 4.7%, from 15 included estimates, and variation between people of 16.1% [17]. At a creatinine of 1.00 mg/dL, 4.4% is about 0.04 mg/dL.
Population: 91 healthy adults aged 21 to 69 at 6 European laboratories [16]. Healthy adults in the studies the database pools [17].
Sources: [16], [17]
Caveats: Variation within one person is about a quarter of the variation between people. The database states no threshold for agreement, so the result is given as numbers only [17].

Thiazide diureticsModerate

Kidney stone prevention

Mixed results: a pooled analysis of 10 trials found 37% fewer stone recurrences on thiazides, and the largest trial found no difference from placebo.

The numbers and sources

Effect: A meta-analysis of 10 randomized trials found fewer stone recurrences on thiazides than placebo (RR 0.63, 95% CI 0.49 to 0.83), with substantial heterogeneity (I² 65%) [12]. In the largest trial, symptomatic or radiologic recurrence occurred in 59% on placebo and in 59%, 56% and 49% on hydrochlorothiazide 12.5, 25 and 50 mg, with no relation between dose and recurrence (P = 0.66) [13].
Population: 650 people on thiazides and 672 on placebo in 10 trials [12]; 416 people with recurrent calcium-containing kidney stones followed a median 2.9 years [13].
Sources: [12], [13]
Caveats: The pooled trials are mostly older and smaller than [13]. Not an FDA-approved use [14].

Uric acid (serum urate)Moderate

Chronic kidney disease, in cohorts and in trials that lowered urate

Mixed results: cohorts link higher uric acid to new kidney disease, while two allopurinol trials found no slowing of kidney function decline.

The numbers and sources

Effect: In a meta-analysis of 13 cohort studies, higher serum uric acid went with more new chronic kidney disease (summary odds ratio 1.15, 95% CI 1.05 to 1.25), and hyperuricemia with an odds ratio of 2.35 (1.59 to 3.46) [18]. In a randomized trial in adults with stage 3 or 4 chronic kidney disease and a mean serum urate of 8.2 mg/dL, eGFR fell by 3.33 mL/min/1.73 m2 a year on allopurinol and 3.23 on placebo (difference -0.10, 95% CI -1.18 to 0.97) [19]. In a randomized trial in people with type 1 diabetes and early kidney disease, allopurinol lowered mean serum urate from 6.1 to 3.9 mg/dL, and measured GFR after 3 years and a 2-month washout did not differ from placebo (difference 0.001 mL/min/1.73 m2, 95% CI -1.9 to 1.9) [20]. KDIGO's 2024 guideline suggests against using urate-lowering drugs to delay kidney disease progression in people with chronic kidney disease whose hyperuricemia causes no symptoms [3].
Population: 190,718 participants in 13 studies [18]. 363 patients analyzed, mean eGFR 31.7 mL/min/1.73 m2 [19]. 530 participants with type 1 diabetes, mean age 51.1 [20].
Sources: [18], [19], [20], [3]
Caveats: The first trial stopped early for slow recruitment after enrolling 369 of 620 intended patients [19]. The cohort finding is observational, and reverse causation, with early kidney decline raising uric acid, cannot be ruled out.

Urine albumin to creatinine ratioModerate

Point-of-care tests against the laboratory

Shown to detect albuminuria with 96% sensitivity for quantitative point-of-care tests and 76% for semiquantitative ones against laboratory measurement.

The numbers and sources

Compared with: Laboratory measurement of the urine albumin to creatinine ratio
Effect: In a meta-analysis of machine-read point-of-care tests, the semiquantitative test had a sensitivity of 76% (95% CI 63% to 86%) and a specificity of 93% (84% to 97%). The quantitative test had a sensitivity of 96% (78% to 99%) and a specificity of 98% (93% to 99%). The authors conclude that a negative semiquantitative result does not rule out albuminuria, and that quantitative point-of-care testing meets required performance standards [15].
Population: 3,356 patients in 16 studies in primary or secondary ambulatory care [15].
Sources: [15]
Caveats: Accuracy was estimated from single urine samples, while guidelines ask for albuminuria to be confirmed on repeat samples [15].

Blood urea nitrogen (BUN)Limited

Variation from one test to the next

Limited evidence: one study put within-person variation of urea at about 11%, roughly twice that of creatinine in the same people.

The numbers and sources

Compared with: Repeat measurement in the same person
Effect: A study of 730 apparently healthy adults in Bangladesh reported within-person variation of 10.72% for urea against 4.64% for creatinine, variation between people of 31.47%, and a reference change value of 30.58%, the size of change between two results that exceeds expected variation [13]. A European study of 91 healthy adults sampled weekly for 10 weeks reported that urea was one of only two analytes whose within-person variation was not lower than older published estimates, and that it differed between men and women [14].
Population: 730 adults aged 18 to 65 [13]. 91 healthy adults aged 21 to 69 at 6 European laboratories [14].
Sources: [13], [14]
Caveats: The first abstract describes a cross-sectional design and does not say how many samples each person gave [13]. The European abstract gives no figures for urea [14]. Neither states a threshold for agreement.

Cystatin CLimited

Variation from one test to the next

One small study found cystatin C varied 8.6% from week to week within a healthy person, more than the 4.7% for creatinine.

The numbers and sources

Compared with: The same person's results on 8 weekly morning draws
Effect: In healthy people, within-person variation was 8.6% for cystatin C and 4.7% for creatinine, with analytical variation of 2.0% and 1.6%. In patients with impaired kidney function it was 16.0% for cystatin C and 8.9% for creatinine. Variation between people was similar for the two tests, 15.1% and 14.4% [22].
Population: 20 healthy people aged 25 to 61 and 19 patients with impaired kidney function aged 35 to 70 [22].
Sources: [22]
Caveats: One laboratory and 39 people. The study states no threshold for agreement, so the result is given as numbers only [22].

Holotranscobalamin (active B12)Limited

Reduced kidney function

Mixed results: an expert panel reports holotranscobalamin is raised in impaired kidney function, while two studies of older adults found little effect.

The numbers and sources

Compared with: People with normal kidney function
Effect: An expert panel states that holotranscobalamin is elevated in people with impaired renal function [17]. In Swiss adults aged 60 and older, kidney function affected methylmalonic acid and homocysteine and not holotranscobalamin (p = 0.12) [6]. In 700 older adults, renal dysfunction compromised the diagnostic accuracy of methylmalonic acid and not that of holotranscobalamin [7].
Population: 1,143 Swiss adults aged 60 and older [6]. 700 adults aged 63 to 97 [7].
Sources: [17], [6], [7]
Caveats: The studies state no threshold for agreement. The panel gives no figure for the size of the rise [17].

2 more

Serum creatinineLimited

Assay method

Limited evidence: alkaline picrate assays measured creatinine about 4 times less repeatably than enzymatic assays in one study, and a US working group reported bias at lower levels.

The numbers and sources

Compared with: Isotope dilution mass spectrometry, the reference method
Effect: In samples from 91 adults run in duplicate, analytical variation was 1.1% for an enzymatic method and 4.4% for an alkaline picrate method, which did not meet the imprecision specification the authors derived [16]. A US kidney education program working group reported in 2006 that variability between creatinine measurements made filtration estimates less accurate below 1.5 mg/dL, that many routine methods met the required precision while bias remained, and that standardizing calibration does not correct interference from other substances [18]. The two survey manuals on this page describe one method of each kind. Both are traceable to the reference method, and they print different reference ranges [2][3].
Population: 91 healthy adults at 6 European laboratories [16]. A review of routine methods by an expert working group [18].
Sources: [16], [18], [2], [3]
Caveats: The working group's report dates from 2006 and sets out a plan for standardizing calibration, so it describes assays as they then were. A laboratory report does not always say which method was used [18].

Urine albumin to creatinine ratioLimited

Variation from one sample to the next

Small studies found the ratio varied about 30% within one person over days to weeks, so a result had to more than double to show a real rise.

The numbers and sources

Compared with: The same person's results on repeat urine samples over days to weeks
Effect: In outpatients with chronic kidney disease sampled at 3 visits within 4 weeks, within-person variation was 32.5% for the ratio in first morning samples and 29.7% in random samples. A rise had to exceed 141% or 124%, and a fall 58% or 55%, to lie outside expected variation [12]. In outpatients sampled at 9 am on consecutive days, the change needed to show a real difference with 95% certainty was 467% for ratios below 27 mg/g, 170% for ratios of 27 to 265 mg/g and 83% for ratios above 265 mg/g [13]. A kidney guideline states that the biological variation of urine albumin exceeds 60% and that, in people being monitored, a doubling of the ratio on a later test exceeds laboratory variability [4].
Population: 50 clinically stable outpatients with chronic kidney disease in the United States, median ratio 173 mg/g [12]. 157 clinically stable outpatients at one Australian hospital clinic [13].
Sources: [12], [13], [4]
Caveats: Both studies enrolled clinic patients, most with kidney disease. Neither states a threshold for agreement, so the result is given as numbers only. The authors of the US study write that the variability makes it difficult to tell random change from meaningful biologic change [12].

Not shown to help16

AllopurinolModerate

Slowing chronic kidney disease

Not shown to slow loss of kidney function in two placebo-controlled trials, in chronic kidney disease and in type 1 diabetes.

The numbers and sources

Effect: In adults with stage 3 or 4 chronic kidney disease, eGFR fell 3.33 mL/min/1.73 m² a year on allopurinol and 3.23 on placebo (difference -0.10, 95% CI -1.18 to 0.97) [9]. In people with type 1 diabetes and early kidney disease, serum urate fell from 6.1 to 3.9 mg/dL on allopurinol and stayed at 6.1 on placebo. Measured GFR after 3 years and a washout did not differ (difference 0.001, 95% CI -1.9 to 1.9), and urinary albumin excretion was 40% higher on allopurinol (95% CI 0 to 80) [10].
Population: 363 adults with chronic kidney disease, no gout and a mean eGFR of 31.7, followed 104 weeks [9]; 530 people with type 1 diabetes and a GFR of 40 to 99.9 [10].
Sources: [9], [10]
Caveats: The first trial stopped recruiting early, at 369 of a planned 620 people [9].

Alpha-blockersModerate

Small ureteral stones in large placebo-controlled trials

Not shown to help small ureteral stones pass in two large trials, where tamsulosin and placebo gave the same rates, 81% against 80% and 50% against 47%.

Compared with placebo and nifedipine [11]; placebo [12]

The numbers and sources

Effect: In a UK trial, 81% on tamsulosin 400 µg, 80% on nifedipine and 80% on placebo needed no further intervention by 4 weeks (adjusted risk difference for tamsulosin 1.3%, 95% CI -5.7 to 8.3) [11]. In a US emergency department trial with a mean stone size of 3.8 mm, 50% passed the stone by day 28 on tamsulosin 0.4 mg and 47% on placebo (RR 1.05, 95.8% CI 0.87 to 1.27), and no secondary outcome differed [12].
Population: 1,136 adults aged 18 to 65 with a single ureteral stone of 10 mm or less at 24 UK hospitals [11]; 497 adults with stones under 9 mm at 6 US emergency departments [12].
Sources: [11], [12]
Caveats: Most stones in both trials were small, the group where the meta-analyses also found little effect [9][10]. The US trial excluded people lost to follow-up before stone passage [12].

Estimated GFR (eGFR)Moderate

Creatine supplements

Shown to raise serum creatinine about 0.13 mg/dL in pooled trials. Creatinine-based GFR estimates fell in one analysis while GFR measured with a tracer did not.

The numbers and sources

Compared with: GFR measured with Cr-EDTA, a tracer method that does not rely on creatinine
Effect: In 26 randomized trials, creatine supplementation raised serum creatinine by 0.14 mg/dL (95% CI 0.05 to 0.22) and lowered GFR assessed by creatinine-based methods by 10.75 mL/min (95% CI -17.48 to -4.02). GFR assessed by Cr-EDTA did not differ significantly (5.89 mL/min, 95% CI -0.30 to 12.08), nor did serum urea, albuminuria or proteinuria [14]. A second meta-analysis of 20 randomized studies found serum creatinine 0.13 mg/dL higher (95% CI 0.07 to 0.18) and no significant difference in eGFR (-5.20 mL/min/1.73 m2, 95% CI -15.00 to 4.60) [15].
Population: 1,036 participants in 26 trials, healthy people and people with chronic kidney disease [14]. 19 randomized trials and one randomized crossover study [15].
Sources: [14], [15]
Caveats: The authors of the first analysis attribute the changes to altered creatinine metabolism, not kidney injury, because the tracer measurement did not change [14]. The two analyses disagree on whether the fall in estimated GFR is statistically significant. The authors of the second call for trials longer than 1 year [15].

Estimated GFR (eGFR)Moderate

A cooked meat meal before the blood draw

Shown to raise serum creatinine and lower eGFR for hours after a cooked meat meal, from a median of 84 to 59.5 in one study.

The numbers and sources

Compared with: The same people's results before the meal and after a meat-free meal
Effect: In 32 people, median serum creatinine rose from 80.5 µmol/L before a cooked meat meal to 101.0 µmol/L 1 to 2 hours after and 99.0 µmol/L at 3 to 4 hours. Median eGFR fell from 84.0 to 59.5 and 64.0 mL/min/1.73 m2. Meat-free meals had little effect, and cystatin C was generally unaffected by food [16]. In 80 people, a standardized cooked meat meal with about 54 g of protein raised serum creatinine and lowered eGFR at every stage of diabetes-related kidney disease studied. Six of 16 people in stage 3a were reclassified as stage 3b, and the effect was gone after a 12-hour fast [17]. KDIGO describes a rise of about 20 µmol/L (0.23 mg/dL) in one study and states that waiting at least 12 hours after eating meat or fish avoids the effect [3].
Population: 17 healthy volunteers and 15 outpatients [16]. 80 people: healthy volunteers and people with diabetes at 4 stages of chronic kidney disease, 16 per group [17].
Sources: [16], [17], [3]
Caveats: Both studies are small, and each used an older estimating equation than the 2021 CKD-EPI equation. The second gives no size for the fall in its abstract [17].

Estimated GFR (eGFR)Moderate

Creatinine-based eGFR against cystatin C-based eGFR

Shown to place fewer people below 60 than cystatin C-based eGFR, 9.7% against 13.7%, and to track death and kidney failure less closely.

The numbers and sources

Compared with: eGFR calculated from cystatin C, alone or combined with creatinine
Effect: In 11 general population studies, 13.7% of people had an eGFR below 60 mL/min/1.73 m2 by cystatin C against 9.7% by creatinine. People moved to a higher eGFR category by cystatin C had lower risk of death, cardiovascular death and end-stage renal disease, and people moved to a lower category had higher risk. The net reclassification improvement with cystatin C was 0.23 (95% CI 0.18 to 0.28) for death and 0.10 (0.00 to 0.21) for end-stage renal disease [19]. Equations that combine creatinine and cystatin C were closer to measured GFR than creatinine-only equations in a separate study [10].
Population: 90,750 participants in 11 general population studies and 2,960 in 5 cohorts with chronic kidney disease [19].
Sources: [19], [10]
Caveats: Cystatin C has its own non-kidney influences. KDIGO names steroid use, thyroid disease and cancer [3]. The study was funded in part by the National Kidney Foundation [19].

NT-proBNPModerate

Kidney function

Shown to run higher with reduced kidney function, where studies used a median cut point of 1,980 pg/mL against 450 with preserved function.

The numbers and sources

Compared with: Diagnostic accuracy in patients with an estimated GFR of 60 or above in the same studies
Effect: In a meta-analysis of studies that reported results by kidney function, most divided patients at an estimated GFR of 60 mL/min per 1.73 m². With reduced kidney function the area under the curve for acute decompensated heart failure ranged from 0.66 to 0.89 at a median cut point of 1,980 pg/mL. With preserved function it ranged from 0.72 to 0.95 at a cut point of 450 pg/mL. The authors conclude that NT-proBNP keeps its usefulness for diagnosis in reduced kidney function at higher cut points [8]. The European guideline lists renal dysfunction among the causes of a raised level [3].
Population: 4,287 patients in 9 diagnostic studies, with 1,325 cases of acute decompensated heart failure [8].
Sources: [8], [3]
Caveats: The cut points varied between the studies and were chosen within each one. None of the guideline ranges on this page is adjusted for kidney function.

Serum creatinineModerate

Creatine supplements

Shown to raise serum creatinine about 0.13 mg/dL in pooled trials, with no significant change in kidney filtering measured by a tracer.

The numbers and sources

Compared with: Kidney filtering measured with Cr-EDTA, a tracer method that does not rely on creatinine
Effect: In 26 randomized trials, creatine supplementation raised serum creatinine by 0.14 mg/dL (95% CI 0.05 to 0.22). Filtering measured by Cr-EDTA did not differ significantly (5.89 mL/min, 95% CI -0.30 to 12.08), nor did serum urea, albuminuria or proteinuria [12]. A second meta-analysis of 20 randomized studies found serum creatinine 0.13 mg/dL higher (95% CI 0.07 to 0.18), with no difference in urea [13].
Population: 1,036 participants in 26 trials, healthy people and people with chronic kidney disease [12]. 19 randomized trials and one randomized crossover study [13].
Sources: [12], [13]
Caveats: The authors of the first analysis attribute the rise to altered creatinine metabolism, not kidney injury, because the tracer measurement did not change. Results across its trials varied widely. The authors of the second call for trials longer than 1 year [12][13].

Serum creatinineModerate

A cooked meat meal before the blood draw

Shown to raise serum creatinine for hours after a cooked meat meal, from a median of 0.91 to 1.14 mg/dL in one study.

The numbers and sources

Compared with: The same people's results before the meal and after a meat-free meal
Effect: In 32 people, median serum creatinine rose from 80.5 µmol/L (0.91 mg/dL) before a cooked meat meal to 101.0 µmol/L (1.14 mg/dL) 1 to 2 hours after and 99.0 µmol/L (1.12 mg/dL) at 3 to 4 hours. Meat-free meals had little effect, and the changes were similar by three assay methods [14]. In 80 people, a standardized cooked meat meal with about 54 g of protein raised serum creatinine at every stage of diabetes-related kidney disease studied, and the effect was gone after a 12-hour fast [15]. A kidney guideline describes a rise of about 0.23 mg/dL in one study, reached by 2 hours in some people and 4 hours in others, and states that waiting at least 12 hours after eating meat or fish avoids the effect [11].
Population: 17 healthy volunteers and 15 outpatients [14]. 80 people: healthy volunteers and people with diabetes at 4 stages of chronic kidney disease, 16 per group [15].
Sources: [14], [15], [11]
Caveats: Both studies are small. The second gives no size for the rise in its abstract. Its authors attribute the rise to creatine in meat that turns to creatinine on cooking and is absorbed [15].

Blood urea nitrogen (BUN)Limited

BUN against creatinine-based kidney measures

Limited evidence: in heart and kidney disease cohorts, BUN predicted death or kidney failure beyond what creatinine-based measures explained.

The numbers and sources

Compared with: Serum creatinine, estimated creatinine clearance and eGFR
Effect: In patients admitted for decompensated heart failure, BUN predicted death while creatinine and estimated creatinine clearance did not after adjustment for other factors [6]. In older Medicare patients, one creatinine-based eGFR equation failed to identify increased risk in 50% of heart attack patients and 60% of heart failure patients, and BUN carried the greatest relative importance for predicting death among the kidney measures compared [7]. In people with chronic kidney disease, BUN was associated with kidney outcomes independent of eGFR [9]. In US veterans, eGFR was not associated with new diabetes when BUN was 25 mg/dL or less, while BUN above 25 mg/dL was, at every level of eGFR [8].
Population: 541 patients with heart failure [6]. 101,089 Medicare patients [7]. 459 patients with chronic kidney disease [9]. 1,337,452 US veterans [8].
Sources: [6], [7], [9], [8]
Caveats: None of these studies compared BUN with directly measured GFR, so they show that BUN and creatinine carry different information, not which is closer to true filtration. The ratio of BUN to creatinine is a separate quantity. In one US survey analysis its association with death from any cause was U-shaped, lowest at a ratio of 11.43 to 14.64 [12]. The ratio is not placed as a range on this page.

C-peptideLimited

Kidney function and blood glucose at the time of the draw

Limited evidence: a review states that impaired kidney function raises C-peptide and low blood glucose lowers it, and Medicare doubles its fasting threshold in kidney disease.

The numbers and sources

Compared with: C-peptide with normal kidney function and no low blood glucose at the draw
Effect: A review states that about half of the C-peptide produced is removed by the kidneys, so blood levels can be falsely elevated in kidney impairment, and that low blood glucose suppresses insulin and C-peptide [4]. Medicare defines insulinopenia as a fasting C-peptide at or below 110% of the lower limit of normal of the laboratory's method, or at or below 200% of that limit when creatinine clearance is 50 mL/min or less, and counts a fasting value only when fasting glucose drawn at the same time is 225 mg/dL or below [2]. The American and European consensus report asks for a repeat test when the result is under 600 pmol/L and glucose at the same time is below 72 mg/dL, and against testing within 2 weeks of a hyperglycemic emergency [12].
Population: No study population. These are statements from a review, a coverage rule and a consensus report [4][2][12].
Sources: [4], [2], [12]
Caveats: None of the three sources gives the size of the shift. The Medicare criterion is set against each laboratory's own lower limit, so it has no single number and is not placed as a range on this page [2].

Estimated GFR (eGFR)Limited

Muscle mass

One study of 170 healthy adults found serum creatinine rose with lean mass while cystatin C, another filtration marker, did not.

The numbers and sources

Compared with: Serum cystatin C measured in the same people
Effect: In 170 healthy adults, serum creatinine correlated with body weight and more strongly with lean mass, and cystatin C correlated with neither. People with moderate or intense physical activity had more lean mass (55.3% against 48.5%) and higher serum creatinine (1.04 against 0.95 mg/dL) than sedentary people, with no difference in cystatin C. Lean mass stayed related to creatinine after adjustment for protein and meat intake and physical activity [11]. KDIGO lists body builders, extreme sport, eating disorders, above-knee amputation and spinal cord injury as settings where creatinine-based eGFR loses accuracy and a cystatin C-based estimate may be appropriate [3]. Laboratories print serum creatinine intervals by sex: 0.67 to 1.17 mg/dL for men and 0.51 to 0.95 for women in a US national survey laboratory manual, and 0.70 to 1.30 and 0.50 to 1.10 in an internal medicine board table [12][13].
Population: 92 women and 78 men, healthy, grouped as sedentary, mildly active or moderately to intensely active [11].
Sources: [11], [3], [12], [13]
Caveats: The study did not measure GFR directly, so it shows that creatinine tracks muscle, not by how much any one eGFR is off [11]. Serum creatinine in mg/dL is a different quantity from eGFR, so its intervals are described here and not placed as ranges on this page.

HematocritLimited

Death and heart attack in a dialysis trial that raised hematocrit to 42%

One trial found raising hematocrit to 42% with epoetin did not cut deaths or heart attacks in hemodialysis patients with heart disease, and the trial was halted.

The numbers and sources

Effect: Patients were assigned to epoetin doses aimed at a hematocrit of 42% or of 30%. After 29 months there were 183 deaths and 19 first nonfatal heart attacks in the 42% group and 150 deaths and 14 nonfatal heart attacks in the 30% group, a risk ratio of 1.3 (95% CI 0.9 to 1.9). The difference did not reach the preset stopping boundary, and the study was halted. Within each group, death rates fell as the hematocrit reached rose [11].
Population: 1,233 people on hemodialysis with heart failure or ischemic heart disease, treated for a median of 14 months [11].
Sources: [11]
Caveats: One trial in people on dialysis with heart disease, in whom hematocrit was raised with a drug. The higher target group also had a decline in the adequacy of dialysis and more intravenous iron, so the trial cannot separate hematocrit from the treatment used to raise it [11].
Why limited: This rests on one trial, of 1,233 people. Strength counts independent studies that agree, so one trial is limited at any size.

4 more

Parathyroid hormone (PTH)Limited

Death and cardiovascular events in a trial of cinacalcet in dialysis patients

One trial found cinacalcet, a drug for raised PTH, did not significantly reduce death or cardiovascular events in dialysis patients: 48.2% against 49.2% on placebo.

The numbers and sources

Effect: In patients on hemodialysis with moderate to severe secondary hyperparathyroidism, the composite of death, heart attack, hospitalization for unstable angina, heart failure or a peripheral vascular event occurred in 938 of 1,948 (48.2%) on cinacalcet and 952 of 1,935 (49.2%) on placebo, a relative hazard of 0.93 (95% CI 0.85 to 1.02, P = 0.11). Low blood calcium and gastrointestinal adverse events were significantly more frequent on cinacalcet [14].
Population: 3,883 patients with a median intact PTH of 693 pg/mL, followed for up to 64 months [14].
Sources: [14]
Caveats: A marker that tracks an outcome is not always one whose correction changes it. This is the unadjusted intention-to-treat result, and the trial was funded by the drug's maker. It studied people with kidney failure and very high PTH, so it says nothing about results near the reference range [14].
Why limited: This rests on one trial, of 3,883 people. Strength counts independent studies that agree, so one trial is limited at any size.

Serum creatinineLimited

Muscle mass

One study of 170 healthy adults found serum creatinine rose with lean mass while cystatin C, another filtration marker, did not.

The numbers and sources

Compared with: Serum cystatin C measured in the same people
Effect: Serum creatinine correlated with body weight and more strongly with lean mass, and cystatin C correlated with neither. People with moderate or intense physical activity had more lean mass (55.3% against 48.5%) and higher serum creatinine (1.04 against 0.95 mg/dL) than sedentary people, with no difference in cystatin C. Lean mass stayed related to creatinine after adjustment for protein and meat intake and physical activity [10]. A kidney guideline lists body builders, extreme sport, eating disorders, above-knee amputation and spinal cord injury as settings where muscle mass alters creatinine apart from kidney function. It also lists anabolic steroids, medications that decrease secretion of creatinine by the kidney tubules, and low-protein, vegetarian, ketogenic and high-protein diets [11].
Population: 92 women and 78 men, healthy, grouped as sedentary, mildly active or moderately to intensely active [10].
Sources: [10], [11]
Caveats: The study did not measure kidney filtering directly, so it shows that creatinine tracks muscle, not by how much any one result is shifted [10]. The reference ranges on this page are printed by sex and not by muscle mass [2][3].

Urine albumin to creatinine ratioLimited

Random daytime sample against a 24-hour collection

One study found random daytime samples classed 22.4% of people as having microalbuminuria against 10.0% by 24-hour collection, while first morning samples gave 7.5%.

The numbers and sources

Compared with: Albumin excretion in three 24-hour urine collections
Effect: Participants each made three 24-hour collections, a first morning sample and a random spot sample. The ratio in the first morning sample agreed most closely with 24-hour albumin excretion. The prevalence of microalbuminuria was 10.0% by 24-hour collection, 7.5% by first morning ratio and 22.4% by random spot ratio. Within-person variation of the first morning ratio was 19%, similar to the 24-hour collection, and was significantly greater for the other measures [14]. A kidney guideline states a preference for the first morning sample and accepts a random sample when none is available [4].
Population: 241 participants in a Dutch cohort study [14].
Sources: [14], [4]
Caveats: One study of 241 people. The US national institute describes the ratio on a spot sample as an estimate of 24-hour albumin excretion that makes timed collections unnecessary [6].

Urine albumin to creatinine ratioLimited

Things that shift the ratio apart from kidney disease

Limited evidence: exercise, menstruation, blood in the urine and urinary infection raise the ratio, and people who excrete less creatinine read higher at the same albumin loss.

The numbers and sources

Compared with: Albumin excretion measured in a timed urine collection
Effect: A kidney guideline lists blood in the urine, menstruation, exercise and symptomatic urinary infection as causes of a falsely elevated ratio. On the creatinine side of the ratio, it lists female sex, low body weight, acute kidney injury and low protein intake as causes of low urinary creatinine and therefore a higher ratio, and male sex, high body weight and high protein intake as causes of a lower ratio. It states that all of these can lead to false detection of chronic kidney disease or its progression [4]. In a US national sample, a single cut point of 30 for both sexes classed 9.2% of women and 6.0% of men as having microalbuminuria, and female sex was independently associated with microalbuminuria (OR 1.62, 95% CI 1.29 to 2.05). The association disappeared with sex-specific cut points [7].
Population: A nationally representative sample of US adults [7]. Factors listed in a guideline table [4].
Sources: [4], [7]
Caveats: The guideline lists the direction of each effect without sizes. It notes that the ratio equals albumin excretion in mg a day only on the assumption that a person excretes about 1 g of creatinine a day [4].

Checked, no increase found7

Protein powderModerate

Kidney function

Kidney filtration change did not differ between higher-protein and normal or lower protein diets in adults without kidney disease.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Across 28 RCTs (1,358 participants), higher-protein diets (1.5 g per kg or more, 20% of energy or more, or 100 g a day or more) gave a slightly higher filtration rate after the intervention (SMD 0.19, 95% CI 0.07 to 0.31), but the change in filtration rate did not differ from normal or lower protein (SMD 0.11, 95% CI -0.05 to 0.27) [17].
Population: Adults without kidney disease [17].
Sources: [17]
Caveats: Diets, not powders specifically. People with kidney disease were excluded. Selection bias risk was unclear in most trials [17].

TirzepatideModerate

Kidney effects

Kidney problems were about as common as on placebo, insulin or GLP-1 drugs, and urine albumin fell at 10 and 15 mg.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Tirzepatide did not raise adverse kidney events, urinary tract infection, kidney stones, acute kidney injury or kidney cancer against placebo, insulin or GLP-1 drugs. Urine albumin fell more than on placebo with 10 mg (MD -26.95%) and 15 mg (MD -18.03%) [31].
Population: 14,471 participants in 15 RCTs over 26 to 72 weeks [31].
Sources: [31]
Caveats: Short trials. Kidney function (eGFR) did not differ from insulin [31].

TurmericModerate

Side effects in trials

Side effects were about as common as on placebo in most trials, though one cognition review found more. Short trials cannot detect rare liver injury.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In osteoarthritis trials, adverse events on turmeric extracts were similar to placebo and 12% fewer than on NSAIDs [1]. In depression trials, digestive (OR 1.27, 95% CI 0.69 to 2.32) and neurological symptoms (OR 1.08) did not differ from control [25]. In COVID-19 trials, adverse events, mostly mild digestive symptoms, were comparable to placebo [40]. In 10 human cognition studies, adverse events were more frequent with curcumin than with control [39]. In 12 RCTs (1,303 people with diabetes), creatinine did not change (WMD -0.01 mg/dL, 95% CI -0.03 to 0.01) [52].
Population: Osteoarthritis, depression, COVID-19, cognition and diabetes RCTs [1][25][40][39][52].
Sources: [1], [25], [40], [39], [52]
Caveats: Trials of 16 weeks or less cannot detect the rare liver injury in the case series. The cognition review abstract does not give adverse event rates [39].

CreatineLimitedStudied in children

Use in adolescents

Limited evidence: no consistent short-term changes in kidney, liver or heart markers in adolescents.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A systematic review of 5 studies, RCTs and cohorts, found no consistent short-term signals in kidney function, liver enzymes or cardiometabolic markers, and no serious adverse events attributed to creatine [21].
Population: Adolescent athletes and physically active youth, including some with medical conditions, in studies published 2015 to 2025 [21].
Sources: [21]
Caveats: Five small studies with short follow-up, found through a PubMed-only search [21].

Horny goat weedLimited

Safety in controlled trials

Small trials in postmenopausal women found no significant adverse symptoms or lab changes. Osteoporosis trials reported mild gut or skin reactions.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In 58 postmenopausal women over 6 weeks, Epimedium prenylflavonoids caused no significant adverse symptoms and no changes in liver, blood or kidney tests [3]. Over 24 months, the icariin blend showed no detectable endometrial hyperplasia [1]. In 10 osteoporosis RCTs, adverse reactions were described as low, mainly mild gastrointestinal reactions or skin allergies [4].
Population: Postmenopausal women [1][3]; patients with osteoporosis [4].
Sources: [1], [3], [4]
Caveats: Trials in women for bone outcomes. No safety data in men using it for sexual function were located.

L-carnitineLimited

Kidney effects

One trial found no change in kidney markers after 12 weeks of L-carnitine in overweight and obese adults.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In 68 overweight and obese adults randomized to control, 1,000 mg of L-carnitine a day, exercise, or both for 12 weeks, creatinine and urea did not change significantly in any group [13]. A review of 8 carnitine studies in athletes and bodybuilders found that kidney risks and benefits have not been evaluated in that group [9].
Population: 68 overweight and obese adults, mean age 29, for 12 weeks [13]. Athletes and bodybuilders [9].
Sources: [13], [9]
Caveats: One small trial with blood markers only, at one dose, with no placebo capsule. The review is narrative, and no study in athletes was located [9].

SaunaLimitedStudied in men

Kidney function

Not linked to chronic kidney disease in 2,071 Finnish men followed for a median 25.7 years.

The numbers and sources

Effect: Comparing 4 to 7 sessions a week with one, estimated glomerular filtration rate, creatinine and sodium did not differ at baseline, and potassium was 0.05 mmol/L higher. Over 25.7 years, 188 men developed chronic kidney disease, with a hazard ratio of 0.84 (95% CI 0.46 to 1.53) [43].
Population: 2,071 men aged 42 to 61 with normal kidney function at baseline [43].
Sources: [43]
Caveats: Observational, one cohort of men, with a wide confidence interval.

Not studied in people2

PQQUntestedHow often is not known

Long-term use

Not studied in people. In female rats, high doses raised kidney weight and urine protein, changes that reversed. Two 13-week rat studies found no treatment-related harm.

No study in people. This rests on animal studies.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In a 14-day rat study, high doses raised relative kidney weight with tissue changes in females only, and a 28-day study in females found more urine protein and crystals. Both reversed during recovery. A 13-week study set a no observed adverse effect level of 100 mg/kg a day, the highest dose tested [8]. A second 13-week study found no treatment-related changes and set the level at 400 mg/kg a day, its highest dose [9]. The longest human trial located ran about 90 days [5].
Population: Rats [8][9].
Sources: [8], [9], [5]
Caveats: Rat studies of 13 weeks or less do not show what years of use do in people. The kidney findings were at high doses.

SGLT2 inhibitorsUntestedHow often is not known

Pregnancy

Not studied in people. Animal studies found reversible kidney changes in young rats exposed during the period matching the second and third trimesters.

No study in people. This rests on animal studies.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In juvenile rats, empagliflozin at about 13 times the maximum clinical dose caused increased kidney weights and dilated kidney tubules and pelvis, which were not seen after a 13-week recovery period. Doses given to rats and rabbits during the period matching the first trimester did not cause developmental harm at up to 48 and 128 times the clinical dose. On this basis the label advises against use in the second and third trimesters [20].
Population: Rats and rabbits [20].
Sources: [20]
Caveats: Animal doses were far above human doses, and no study in pregnant women was sourced.