Inulin and Other Renal Function Biomarkers: Current Standards, Practical Alternatives, And Emerging Approaches

Accurate assessment of glomerular filtration rate is essential for diagnosing and staging chronic kidney disease, evaluating potential kidney donors, adjusting drug doses, and monitoring renal function in critically ill patients. Inulin clearance remains the physiologic reference method for measured glomerular filtration rate because inulin is freely filtered by the glomerulus and is neither reabsorbed, secreted, nor metabolized by the kidney. However, its requirement for continuous infusion, timed blood and urine collection, and technically demanding laboratory procedures limits routine clinical use. Iohexol plasma clearance has emerged as the most practical and extensively validated exogenous alternative, offering acceptable accuracy, low toxicity, and simpler sampling protocols. Endogenous biomarkers, particularly serum creatinine and cystatin C, remain the basis of routine estimated glomerular filtration rate equations. Creatinine is inexpensive and widely available but is affected by muscle mass, diet, age, sex, and tubular secretion. Cystatin C is less dependent on muscle mass but may be influenced by inflammation, corticosteroid exposure, obesity, smoking, and thyroid dysfunction. Combined creatinine–cystatin C equations generally provide greater accuracy than either biomarker alone. Emerging biomarkers, including D-serine, D-asparagine, and proenkephalin, may improve kidney function assessment in selected populations but remain investigational. This review summarizes the physiologic basis, clinical utility, limitations, and future role of inulin and other markers used to measure or estimate renal function.