Cystatin C in chronic kidney disease: enhancing diagnostic accuracy and patient outcomes

Chronic kidney disease (CKD) is a global health challenge affecting more than 850 million people worldwide. Early and accurate assessment of kidney function is crucial for timely diagnosis and management. While serum creatinine (SCr) has traditionally been the primary biomarker for estimating glomerular filtration rate (GFR), it is influenced by factors such as muscle mass, age, sex, and diet, among others, leading to potential inaccuracies. This review evaluates the biological basis, clinical performance, and limitations of cystatin C as an alternative and complementary biomarker to serum creatinine for estimating GFR in CKD. We reviewed epidemiologic, mechanistic, and clinical studies examining cystatin C metabolism, assay methodologies, and its performance in estimating GFR and predicting CKD-related outcomes. Evidence comparing creatinine-based, cystatin C–based, and combined eGFR equations was synthesized. Cystatin C, a low-molecular-weight protein produced by all nucleated cells, is less influenced by muscle mass and dietary factors than creatinine. Cystatin C based and combined creatinine–cystatin C eGFR equations demonstrate improved accuracy for detecting early CKD and more reliably predict CKD progression, cardiovascular events, and mortality. However, cystatin C levels may be affected by thyroid dysfunction, corticosteroid use, inflammation, smoking, obesity, and malignancy, requiring careful interpretation. Cystatin C provides important diagnostic and prognostic information beyond serum creatinine alone and enhances the accuracy of GFR estimation when used in combination with creatinine. Its integration into clinical practice may improve CKD detection and risk stratification, particularly in populations where creatinine-based estimates are unreliable.