Cystatin C

Cystatin C is a small (13 kDa) cysteine protease inhibitor produced at a constant rate by all nucleated cells, freely filtered by the glomerulus, and almost entirely reabsorbed and catabolized by the proximal tubule, making it a sensitive endogenous filtration marker. Unlike creatinine, its serum concentration is minimally influenced by muscle mass, sex, or dietary protein, though it rises with higher body fat, thyroid dysfunction, and corticosteroid use, which should be considered in interpretation. The 2021 CKD-EPI cystatin C and creatinine-cystatin C equations provide more accurate eGFR estimates in populations where creatinine is confounded by muscle mass extremes. Elevated cystatin C is a robust predictor of cardiovascular events, cognitive decline, and all-cause mortality, and epidemiological analyses suggest it may track true renal aging more faithfully than creatinine-derived eGFR.