Glomerular Filtration Rate (GFR) Estimation with Cystatin C—Past, Present, and Future

BACKGROUND: Cystatin C is a long-established filtration marker which can be used to assess kidney function, but it has been sparingly used for clinical care due to creatinine's role as the primary biomarker for kidney function assessment based on estimated glomerular filtration rate (eGFR). CONTENT: This review summarizes the evolution of cystatin C's role in kidney disease assessment and highlights new guidelines promoting more widespread use. Specifically, the 2021 National Kidney Foundation and American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease report, and the 2024 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD), recommend increased use of cystatin C as an alternative and complementary biomarker for kidney function assessment, since it does not differ by race like creatinine, correlates better with adverse outcomes compared to creatinine, and provides a more accurate eGFR when used in combination with creatinine. SUMMARY: While robust literature demonstrates improved accuracy with cystatin C-based eGFR (eGFRcys) in certain clinical subpopulations, future research is needed to better understand its performance relative to creatinine-based eGFR (eGFRcr) and measured glomerular filtration rate (mGFR) in additional diverse cohorts, and to achieve assay standardization to match the performance of creatinine assays. Additionally, cystatin C testing availability will need to be broadened from primarily reference laboratories to local laboratories, and partnerships will need to be developed between clinical stakeholders and the laboratory to promote cystatin C's clinical use, to achieve widespread adoption of guideline-recommended eGFR equations.