Beyond Microalbuminuria: A Narrative Review of Inflammatory, Tubular, Glomerular, and Oxidative Stress Biomarkers for Early Diabetic Kidney Disease

Purpose Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, with a rapidly rising burden in India. Microalbuminuria and estimated glomerular filtration rate (eGFR) detect disease only after substantial irreversible nephron loss, and up to 70% of diabetic patients with declining renal function remain normoalbuminuric. This narrative review critically examines evidence published mainly from 2018 onward on newer serum and urinary biomarkers for early DKD detection and progression risk stratification, with emphasis on applicability within Indian clinical practice. Methods Literature was searched across PubMed, Scopus, and Web of Science; IndMED and Google Scholar were additionally consulted for Indian studies. Biomarkers were grouped by pathophysiological category: inflammation, tubular damage, glomerular and podocyte injury, oxidative stress, and other emerging indicators. Results Soluble tumour necrosis factor receptor 1 (sTNFR1), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) emerged as the most reproducibly validated candidates for pre-albuminuric detection. sTNFR1 demonstrated predictive performance comparable to the combined UACR-eGFR model (AUC 0.73 versus 0.71), operating independently of conventional markers. Multi-marker panels raised the C-statistic for progression prediction from 0.835 to 0.896. Circulating microRNAs, CD146, nephrin, and podocalyxin showed encouraging preliminary results awaiting larger-cohort validation. Conclusion Stepwise incorporation of cystatin C, urinary KIM-1, urinary NGAL, and serum sTNFR1 into Indian clinical biochemistry workflows would meaningfully improve upon albuminuria-based screening alone. Assay standardisation, cost-effectiveness analyses, and population-specific reference intervals remain priorities for Indian laboratories.