CYSTATIN C - Recommended for assessment of GFR and kidney function

06. May 2022 | 8 min read

CYSTATIN C - Recommended for assessment of GFR and kidney function

Analysing cystatin C and creatinine together can give the physician more accurate information on the patient’s eGFR than creatinine alone. The National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) has, in a joint taskforce, recently recommended increasing the use of cystatin C combined with serum (blood) creatinine, as a confirmatory assessment of GFR or kidney function to secure unbiased diagnostics.


A better estimated Glomerular Filtration Rate (eGFR)1-2

While the clinical use of cystatin C can have far-reaching benefits across all patient groups, certain vulnerable patient populations may experience a greater benefit. Specifically, children, amputees and the elderly can receive more accurate eGFRs with cystatin C, since cystatin C is less susceptible to factors that affect muscle mass, like age, diet, sex, race, physical activity, etc.3,4.

Clinical use of cystatin C is recommended in guidelines published by KDIGO5. The National Kidney Foundation (NKF) in the US and the American Society of Nephrology (ASN) have also recently, in a joint taskforce, recommended to increase the use of cystatin C combined with serum (blood) creatinine as a confirmatory assessment of GFR or kidney function6.

Removing the race factor from creatinine equations

The NKF-ASN task force also suggests removing the race factor from the creatinine equations3. The removal of the race factor introduces systematic misclassification that cannot be eliminated even when numerous non-GFR determinants of the serum creatinine level are accounted for7. Cystatin C based eGFR equations are without a race factor and cystatin C can be used together with creatinine, or on its own, to calculate the eGFR without the race factor. The most accurate results will be with the combination of cystatin C and creatinine8.


validation kit cystatin c

The ideal combination with creatinine

Serum creatinine levels are only elevated after about 50% of renal function is lost9. This insensitivity to mild renal insufficiency within what is known as the creatinine blind area (30-70 ml/min/1.73 m2) could give a false sense of security that in-tern leads to under diagnosis of chronic kidney disease (CKD) stages 1 and 2. Depending on creatinine alone to assess kidney function may therefore prevent detection of a variety of renal diseases for which early treatment is critical10.

GFR estimating equations that incorporate both creatinine and cystatin C values together are more accurate than equations that use either marker alone7,11. Using cystatin C in conjunction with creatinine to risk stratify CKD patients can allow for better allocation resources such as nephrology referrals, medication dosage adjustments and more invasive kidney function tests12. Use of cystatin C in combination with creatinine has also been shown to strengthen the association between eGFR and risk of cardiovascular disease, progression into end-stage renal disease and death13.

Cystatin C with stronger correlation with mGFR:

The graphs to the left illustrate the stronger correlation observed between cystatin C serum concentrations and iohexol clearance rates relative to that which is seen with creatinine. This improved correlation can be of clinical significance and lead to improved patient care14.



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  1. Dharnidharka VR et al. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysisAm J Kidney Dis. 2002
  2. Ebert N, Shlipak MG. Cystatin C is ready for clinical useCurr Opin Nephrol Hypertens. 2020
  3. Tangri N et al. Changes in dietary protein intake has no effect on serum cystatin C levels independent of the glomerular filtration rateKidney Int. 2011
  4. Grubb A. Cystatin C is Indispensable for Evaluation of Kidney DiseaseEJIFCC. 2017
  5. KDIGO Guidelines 2012 published in Kidney International Supplements Vol3 Issue 1, Jan 2013
  6. Miller WG et al. National Kidney Foundation Laboratory Engagement Working Group Recommendations for Implementing the CKD-EPI 2021 Race-Free Equations for Estimated Glomerular Filtration Rate: Practical Guidance for Clinical LaboratoriesClin Chem. 2022
  7. Hsu CY et al. Race, Genetic Ancestry, and Estimating Kidney Function in CKDN Engl J Med. 2021
  8. Delgado C et al. Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report From the NKF-ASN Task ForceAm J Kidney Dis. 2021
  9. Gounden V, BH, Jialal, StatPearls. 2021, StatPearlsPublishing.
  10. Schaeffner ES et al. Two novel equations to estimate kidney function in persons aged 70 years or olderAnn Intern Med. 2012
  11. Inker LA et al. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without RaceN Engl J Med. 2021
  12. Murty MS, Sharma UK, Pandey VB, Kankare SB. Serum cystatin C as a marker of renal function in detection of early acute kidney injuryIndian J Nephrol. 2013
  13. Shlipak MG et al. Cystatin C versus creatinine in determining risk based on kidney functionN Engl J Med. 2013
  14. Flodin M et al. Evaluation of Gentian cystatin C reagent on Abbott Ci8200 and calculation of glomerular filtration rate expressed in mL/min/1.73 m(2) from the cystatin C values in mg/LScand J Clin Lab Invest. 2007

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