Amy Carpenter
May 2026—Cystatin C has notable advantages over serum creatinine as a biomarker of kidney filtration: fewer nonglomerular filtration rate determinants, more accurate dosing of medications with narrow therapeutic windows for individuals with obesity or low muscle mass, and greater accuracy in determining eligibility for a kidney transplant or for a simultaneous liver-kidney or heart-kidney transplant.
The National Kidney Foundation and American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases recommends greater use of cystatin C-based GFR estimation. And the 2024 Kidney Disease: Improving Global Outcomes guideline recommends use of a GFR estimate based on the combination of creatinine and cystatin C, if the latter is available, for chronic kidney disease staging.
The number of laboratories that are bringing the test in-house has grown. Last year, more than 400 laboratories were enrolled in the CAP cystatin C Survey, compared with fewer than 50 in 2005. This year enrollment tops 500.
“If you’re not on the train already, it may be time to jump on the train,” said Amy Karger, MD, PhD, D(ABCC), professor in the Department of Laboratory Medicine and Pathology at the University of Minnesota and director since 2015 of central laboratory testing for the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration.
Dr. Karger spoke at last year’s ADLM meeting about the barriers to widespread use of cystatin C and how to bring them down.
The cystatin C assay market is predicted to exceed $421 million by 2030, she said, owing to an aging population and increasing prevalence of chronic kidney disease, as well as greater assay accuracy.
The first manual cystatin C immunoassay was developed in 1979, relied on in-house reagents, and was used only for research. Cystatin C was first used clinically in 1993 in Europe, with commercially available antibodies. The first FDA-approved assay was available in the U.S. in 2001. “There were very different numerical results being reported by those assays and different normal ranges,” Dr. Karger said.
Certified reference material (ERM-DA471/IFCC) became available in 2010. “To my knowledge, all major FDA-approved cystatin C manufacturers now have at least one method traceable to the reference material,” she said, adding that a laboratory that uses one of the less common cystatin C reagents should ensure its traceability.
“While we have a reference material for cystatin C,” she said, “we do not have a certified reference method.” Creatinine has both.
The CAP used its 2019 cystatin C Survey to determine if the methods were in better agreement and whether the accuracy of cystatin C measurements in participating laboratories improved since 2014 (Karger AB, et al. Arch Pathol Lab Med. 2022;146[10]:1218–1223).
Three proficiency testing samples had been sent to participants in the 2014 cystatin C Survey. The CAP repeated the exercise in 2019. Two fresh frozen serum pools, the first from healthy donors without chronic kidney disease and the second from patients with CKD, were sent to 2019 CYS-A Survey participants. “They were not artificially created proficiency testing samples, so they were confident there wouldn’t be matrix effects from those samples,” said Dr. Karger, who is vice chair of the CAP Accuracy-Based Programs Committee.