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Are two biomarkers better than one in kidney health?

Written by Kristin Hart | Apr 7, 2025 9:47:08 AM

Kidney function assessment with cystatin c and creatinine

Estimated glomerular filtration rate (eGFR) plays a crucial role in assessing kidney function and guiding clinical decisions, and is especially important in diagnosing chronic kidney disease (CKD).1 Today eGFR is most often calculated using the biomarker serum creatinine alone (CKD-EPI creatinine equation). Creatinine is a widely used and cost-effective biomarker, it can, in some cases, offer an incomplete assessment of kidney function.

Kidney health advocates and organisations suggest that combining two biomarkers - cystatin C and creatinine - can improve the accuracy and clinical utility of kidney function estimates.

So, are two biomarkers better than one?

 

Creatinine: widely used, but not without limitations

Creatinine is a by-product of muscle metabolism2, and its levels in the blood can be influenced by several non-renal factors, including age, gender, ethnicity, muscle mass and diet (e.g., meat, creatine intake).3-7 These variables can lead to over- or underestimation of kidney function, particularly in populations such as:

  • Older adults/elderly
  • Patients with muscle-wasting conditions
  • Paediatric patients
  • Amputees
  • Critically ill individuals
  • Individuals with risk factors for kidney disease complications

Serum creatinine levels typically rise only after ~50% of renal function is lost, creating a “blind area” (30–70 mL/min/1.73 m²) where early CKD may go undetected.5 Relying on creatinine alone can delay diagnosis and timely intervention.

 

 

Cystatin C: A More accurate biomarker for CKD

Cystatin C is a low-molecular-weight protein produced at a constant rate by all nucleated cells. It is freely filtered by the glomeruli and metabolised in the proximal tubules, with negligible reabsorption into the bloodstream.6,8 Unlike creatinine, cystatin C levels are largely unaffected by non-GFR factors such as muscle mass, sex, age, and dietary protein intake.3-5,9

This physiological stability makes cystatin C a more reliable indicator of kidney function, particularly in patients where creatinine-based estimates may be misleading. In the context of CKD, this improved precision is critical for detecting early-stage renal impairment and ensuring accurate staging. By enhancing diagnostic accuracy, cystatin C enables more informed clinical decisions, better risk stratification, and more personalised treatment strategies for patients with CKD.

However, it is important to acknowledge that cystatin C is not without limitations. Its levels may be influenced by factors such as corticosteroid use, hyperthyroidism, smoking, and obesity—considerations that clinicians should account for when interpreting results.

 

 

The power of combination: cystatin C and creatinine

Using cystatin C alongside creatinine for eGFR assessment offers a more accurate and dependable evaluation of kidney function. Using both biomarkers in combination offers several clinical benefits:

  • Earlier detection of CKD
  • Improved diagnostic accuracy
  • Reduced variability in eGFR estimation
  • Better dosing of medications

Studies have shown that adding cystatin C can reclassify a significant portion of patients into more appropriate CKD stages, leading to better-informed clinical decisions.10

 

Clinical guidelines support the combination of the two biomarkers

Leading international organisations have updated their recommendations adding cystatin C alongside creatinine:

 

Are the two biomarkers better than one?

Yes, particularly when the goal is to improve diagnostic precision, patient outcomes, and resource allocation in kidney health.


The combination of cystatin C and creatinine represents a smarter, evidence-based approach to eGFR estimation. For healthcare providers looking to elevate kidney diagnostics, it's time to consider adding cystatin C to the equation. 


Gentian Cystatin C Immunoassay

Broadly compatible. Clinically trusted. High-performance.

The Gentian Cystatin C Immunoassay is a turbidimetric assay designed for use on most automated clinical chemistry analysers. As an open-channel assay, it can be easily integrated into a wide range of clinical chemistry platforms for flexible, high-throughput testing.

  • FDA 510(k) cleared since 2008

  • CE-marked and IVDR-certified (CE 0123)

  • Developed and manufactured in Norway

  • Utilises avian antibodies to reduce interference

Trusted globally and shipped from within the U.S, the Gentian Cystatin C Immunoassay offers a robust solution for enhancing kidney function diagnostics, supporting clinical decision-making with precision and consistency.

 

 

Visit Gentian at SCM25 at booth #921 to discuss:

  • Clinical case studies and data
  • How cystatin C testing can be seamlessly integrated into your lab
  • Practical implementation support

 

Get in touch about cystatin C

Interested in learning more about the Gentian Cystatin C Immunoassay or the clinical value of cystatin C in kidney diagnostics?

Fill out the form below or email us directly at marketing@gentian.com  — we’d be happy to answer your questions and provide additional resources.

 

References:

  1. Levey AS et al. A New Equation to Estimate Glomerular Filtration Rate. Annals of Internal Medicine. 2009
  2. Mussap M and M Plebani. Biochemistry and clinical role of human cystatin C. Crit Rev Clin Lab Sci. 2004
  3. Tangri N et al. Changes in dietary protein intake has no effect on serum cystatin C levels independent of the glomerular filtration rate. Kidney Int. 2011
  4. Grubb A. Cystatin C is Indispensable for Evaluation of Kidney DiseaseEJIFCC. 2017
  5. Schaeffner E et al. Two novel equations to estimate kidney function in persons aged 70 years or olderAnn Intern Med. 2012
  6. Ebert N and MG Shlipak. Cystatin C is ready for clinical use. Curr Opin Nephrol Hypertens. 2020
  7. Aakjær M et al. Differences in Kidney Function Estimates Based on Creatinine and/or Cystatin C in Non-Traumatic Amputation Patients and Their Impact on Drug Prescribing. J Clin Med. 2019
  8. Hsu CY et al. Race, Genetic Ancestry, and Estimating Kidney Function in CKD. N Engl J Med. 2021
  9. Delgado C et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney DiseaseAm J Kidney Dis. 2022
  10. Gottlieb ER et al. Estimated GFR With Cystatin C and Creatinine in Clinical Practice: A Retrospective Cohort Study. Kidney Medicine. 2023