Milestones in Kidney Function Testing: Reflecting on the Journey Toward Serum Creatinine Measurement Standardization and Its Impact on Chronic Kidney Disease Diagnosis and Management.

Abstract

Accurate measurement of serum creatinine is essential for estimating glomerular filtration rate (GFR), which is central to chronic kidney disease (CKD) detection, staging, and management. However, historical biases in creatinine measurement among several instrument/assay manufacturers compromised estimated GFR (eGFR) reliability, hindering CKD detection and management. Initiatives led by the National Kidney Disease Education Program (NKDEP) Laboratory Working Group and other stakeholders have standardized calibration of creatinine measurement and reporting of eGFR. To summarize the journey toward global standardization of serum creatinine measurement procedures, detailing the coordinated efforts that led to calibration traceability to the NIST (National Institute of Standards and Technology) SRM (standard reference material) 967 reference material, examining the role of proficiency testing in monitoring progress, and contrasting the current state of creatinine assay standardization with that of other key kidney function biomarkers, such as cystatin C and urine albumin. A comprehensive review of peer-reviewed literature from 2005-2025 was conducted, including landmark studies from the Archives of Pathology & Laboratory Medicine, Clinical Chemistry, and clinical practice guidelines from several professional organizations. College of American Pathologists proficiency testing and LN24 survey data were included. The global creatinine standardization initiative, driven by the NKDEP Laboratory Working Group, has dramatically reduced intermethod bias in serum creatinine measurement procedures, vastly improving the reliability of eGFR. While the metrologic traceability of calibration for creatinine measurement is now harmonized, challenges with analytical specificity, particularly for Jaffe-based methods, remain. The success of creatinine standardization serves as an important model for ongoing efforts to harmonize cystatin C and urine albumin measurements, ultimately leading to more accurate, equitable, and standardized care for patients with or at risk for CKD.