Cystatin C
Cystatin C is a blood protein the kidneys filter, used beside creatinine to estimate kidney function. Equations combining the two matched measured kidney function more closely than either alone. Higher levels go with more deaths and heart disease, but a genetic study found no causal role. Published upper limits run from 0.92 to 1.12 mg/L, and assays differed by 14%.
Checked 2026-11-13
- Status
- A blood test run by clinical laboratories, ordered by a clinician. FDA classifies cystatin C tests with creatinine test systems, as class II devices [1]. The 2024 kidney guideline of Kidney Disease: Improving Global Outcomes states that when cystatin C is available the kidney function category is to be estimated from creatinine and cystatin C combined [2]. A 2021 task force of the National Kidney Foundation and American Society of Nephrology called for national efforts toward increased, routine and timely use of cystatin C [3].
- Measures
- The concentration in blood of cystatin C, a small protein the kidneys filter, which is used beside creatinine to estimate the glomerular filtration rate [2][4].
- Also called
- cystatin C, serum cystatin C, plasma cystatin C, CysC, Cys C, cystatin, SCys, eGFRcys, cystatin C eGFR, cystatin C with eGFR, eGFRcr-cys
- Tested for
- kidney function, confirming a creatinine-based eGFR, kidney function in people with high or low muscle mass, kidney function while taking creatine, chronic kidney disease staging, drug dosing, heart disease risk
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
Linked in research3
- StrongLinked 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.
- StrongLinked to more cardiovascular disease at higher levels, about 82% more for each doubling of cystatin C across 16 pooled cohorts.
- ModerateLinked 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.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in mg/L. Where sources differ, each is shown.
Reference intervals in healthy UK blood donors, 2000, adults under 50
Healthy adults under 50, men and women · [5]
| Range | What the source calls it |
|---|---|
| below 0.53 mg/L | No name given |
| 0.53 to 0.92 mg/L | "reference interval" |
| above 0.92 mg/L | No name given |
A reference interval from one study, the central 95% of results in healthy blood donors, so 1 in 20 healthy people falls outside it. It was not set against kidney failure or any other outcome. The study had 309 donors across all ages and found the difference between men and women small enough for a single range. It predates the international reference material for cystatin C, certified in 2010 [6], and in a 2014 US survey one widely used method read 0.78 mg/L on a pool with a target of 0.96 mg/L [7], so an older interval may not fit a result from a current assay.
Reference intervals in healthy UK blood donors, 2000, adults over 50
Healthy adults over 50, men and women · [5]
| Range | What the source calls it |
|---|---|
| below 0.58 mg/L | No name given |
| 0.58 to 1.02 mg/L | "reference interval" |
| above 1.02 mg/L | No name given |
The same study's interval for donors over 50. For all donors together it gives 0.51 to 0.98 mg/L, for women 0.49 to 0.94 and for men 0.56 to 0.98 [5]. A French study of 1,223 apparently healthy people reported means and standard deviations in place of intervals: 0.74 (0.100) mg/L in men and 0.65 (0.085) in women aged 20 to 59, 0.83 (0.103) at 60 and older and 0.75 (0.089) at ages 4 to 19 [8]. Both studies predate the international reference material [6].
US national survey definition of an increased level, 2008
People aged 12 and older in the US general population · [9]
| Range | What the source calls it |
|---|---|
| 1.12 or below mg/L | No name given |
| above 1.12 mg/L | "increased" |
A definition used by the authors of one survey analysis, not a diagnostic range. By it, an increased level was found in 1% of people under 20, 41% of people aged 60 and older and more than 50% of those aged 80 and older. The overall median was 0.85 mg/L, and levels were higher in males and in non-Hispanic white people even among healthy 20 to 39 year olds. Cystatin C was measured in 2006 on stored samples by a nephelometric assay, before the international reference material was certified [9][6].
Cardiovascular Health Study definition of an elevated level, 2006
Elderly adults whose creatinine-based eGFR is 60 mL/min/1.73 m2 or above · [10]
| Range | What the source calls it |
|---|---|
| below 1 mg/L | No name given |
| 1 or above mg/L | "elevated" |
A cut point used by the authors of one US cohort study, not a diagnostic range. The mean level in the cohort was 1.0 mg/L. People without chronic kidney disease whose level was 1.0 mg/L or above had a 4-fold risk of progressing to chronic kidney disease after 4 years, compared with those below it. The study did not measure kidney function directly, and it predates the international reference material [10][6].
What has been shown to move it
Tested, and not shown to change it1
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].
How it compares with the reference method
Matched the reference method1
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].
Mixed results3
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].
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.
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].
What studies tie it to
Linked in research3
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.
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].
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.
Checked, no link found1
Cardiovascular disease in genetic studies
Not shown to cause cardiovascular disease in a genetic study: people with a variant that lowers cystatin C had the same risk.
The numbers and sources
- Effect
- In a Mendelian randomization analysis using a common variant in the cystatin C gene, each copy of which lowered serum cystatin C by 6.13%, the causal relative risk of cardiovascular disease was 1.00 per doubling of cystatin C (95% CI 0.82 to 1.22). This differed significantly from the observational estimate of 1.82. No causal effect was detected for coronary heart disease, ischemic stroke or heart failure taken singly [16].
- Population
- Genetic data from 43 studies with 252,216 participants and 63,292 cardiovascular events [16].
- Sources
- [16]
- Caveats
- One analysis using a single variant that explained 2.8% of the variation in cystatin C. It tests cystatin C itself as a cause and does not test kidney function, which cystatin C is measured to reflect [16].
Sources
- US Food and Drug Administration. Device classification entry for cystatin C tests (product code NDY, class II), read through the openFDA device API, with 21 CFR 862.1225, Creatinine test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-862.1225
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International. 2024. https://doi.org/10.1016/j.kint.2023.10.018
- Delgado C, Baweja M, Crews DC, et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. Journal of the American Society of Nephrology. 2021. https://doi.org/10.1681/ASN.2021070988
- Inker LA, Schmid CH, Tighiouart H, et al. Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C. New England Journal of Medicine. 2012. https://doi.org/10.1056/NEJMoa1114248
- Finney H, Newman DJ, Price CP. Adult reference ranges for serum cystatin C, creatinine and predicted creatinine clearance. Annals of Clinical Biochemistry. 2000. https://doi.org/10.1258/0004563001901524
- Grubb A, Blirup-Jensen S, Lindström V, et al. First certified reference material for cystatin C in human serum ERM-DA471/IFCC. Clinical Chemistry and Laboratory Medicine. 2010. https://doi.org/10.1515/CCLM.2010.318
- Eckfeldt JH, Karger AB, Miller WG, Rynders GP, Inker LA. Performance in Measurement of Serum Cystatin C by Laboratories Participating in the College of American Pathologists 2014 CYS Survey. Archives of Pathology and Laboratory Medicine. 2015. https://doi.org/10.5858/arpa.2014-0427-CP
- Galteau MM, Guyon M, Gueguen R, Siest G. Determination of Serum Cystatin C: Biological Variation and Reference Values. Clinical Chemistry and Laboratory Medicine. 2001. https://doi.org/10.1515/CCLM.2001.141
- Köttgen A, Selvin E, Stevens LA, et al. Serum Cystatin C in the United States: The Third National Health and Nutrition Examination Survey (NHANES III). American Journal of Kidney Diseases. 2008. https://doi.org/10.1053/j.ajkd.2007.11.019
- Shlipak MG, Katz R, Sarnak MJ, et al. Cystatin C and Prognosis for Cardiovascular and Kidney Outcomes in Elderly Persons without Chronic Kidney Disease. Annals of Internal Medicine. 2006. https://doi.org/10.7326/0003-4819-145-4-200608150-00003
- Shlipak MG, Sarnak MJ, Katz R, et al. Cystatin C and the Risk of Death and Cardiovascular Events among Elderly Persons. New England Journal of Medicine. 2005. https://doi.org/10.1056/NEJMoa043161
- Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C versus Creatinine in Determining Risk Based on Kidney Function. New England Journal of Medicine. 2013. https://doi.org/10.1056/NEJMoa1214234
- Lees JS, Welsh CE, Celis-Morales CA, et al. Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease. Nature Medicine. 2019. https://doi.org/10.1038/s41591-019-0627-8
- Estrella MM, Ballew SH, Sang Y, et al. Discordance in Creatinine- and Cystatin C-Based eGFR and Clinical Outcomes: A Meta-Analysis. JAMA. 2025. https://doi.org/10.1001/jama.2025.17578
- Stevens LA, Schmid CH, Greene T, et al. Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney International. 2009. https://doi.org/10.1038/ki.2008.638
- van der Laan SW, Fall T, Soumaré A, et al. Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study. Journal of the American College of Cardiology. 2016. https://doi.org/10.1016/j.jacc.2016.05.092
- Inker LA, Eneanya ND, Coresh J, et al. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. New England Journal of Medicine. 2021. https://doi.org/10.1056/NEJMoa2102953
- Pottel H, Björk J, Rule AD, et al. Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex. New England Journal of Medicine. 2023. https://doi.org/10.1056/NEJMoa2203769
- Baxmann AC, Ahmed MS, Marques NC, et al. Influence of Muscle Mass and Physical Activity on Serum and Urinary Creatinine and Serum Cystatin C. Clinical Journal of the American Society of Nephrology. 2008. https://doi.org/10.2215/CJN.02870707
- Fricker M, Wiesli P, Brändle M, Schwegler B, Schmid C. Impact of thyroid dysfunction on serum cystatin C. Kidney International. 2003. https://doi.org/10.1046/j.1523-1755.2003.00925.x
- Karger AB, Long T, Inker LA, Eckfeldt JH. Improved Performance in Measurement of Serum Cystatin C by Laboratories Participating in the College of American Pathologists 2019 CYS Survey. Archives of Pathology and Laboratory Medicine. 2022. https://doi.org/10.5858/arpa.2021-0306-CP
- Reinhard M, Erlandsen EJ, Randers E. Biological variation of cystatin C and creatinine. Scandinavian Journal of Clinical and Laboratory Investigation. 2009. https://doi.org/10.3109/00365510903307947