SUN-611 - Urinary Nephrin as an Early Biomarker of Diabetic Kidney Disease: A Systematic Review and Meta-Analysis

Background
Diabetic kidney disease (DKD) remains a leading cause of chronic kidney disease worldwide, with early glomerular injury often preceding clinically overt albuminuria. Podocyte dysfunction is a key pathogenic event in DKD, and nephrin, a critical slit diaphragm protein, has emerged as a promising urinary biomarker reflecting podocyte injury. While increased urinary nephrin has been reported in diabetes, its discriminatory ability across stages of albuminuria and relative to non-diabetic controls remains incompletely assessed.
Objective
To systematically evaluate and quantify differences in urinary nephrin levels among (1) diabetic patients with microalbuminuria versus diabetic patients with normoalbuminuria, and (2) diabetic patients with normoalbuminuria versus non-diabetic controls.
Methods
A systematic review and meta-analysis was conducted following PRISMA guidelines. Eligible studies included observational studies reporting urinary nephrin levels in adults with diabetes stratified by albuminuria status, as well as non-diabetic control groups. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a random-effects inverse-variance model. Heterogeneity was assessed using the I² statistic and Cochran’s Q test. Statistical significance was defined as a two-sided p < 0.05.
Results
Eight studies comparing diabetic patients with microalbuminuria (n = 266) to diabetic patients with normoalbuminuria (n = 302) were included. Urinary nephrin levels were significantly higher in the microalbuminuric group (pooled SMD 1.28, 95% CI 0.61–1.95; p = 0.0002), with substantial heterogeneity (I² = 92%). Seven studies comparing diabetic patients with normoalbuminuria (n = 263) to non-diabetic controls (n = 237) demonstrated markedly elevated urinary nephrin levels in normoalbuminuric diabetic patients (pooled SMD 3.59, 95% CI 2.28–4.90; p < 0.00001), again with high heterogeneity (I² = 96%).
Conclusions
Urinary nephrin levels are significantly elevated across the spectrum of diabetic kidney disease, including in diabetic patients with normoalbuminuria, and further increase with the development of microalbuminuria. These findings support urinary nephrin as a sensitive biomarker of early podocyte injury that may precede conventional markers such as albuminuria. This meta-analysis underscores the potential clinical utility of urinary nephrin in early DKD risk stratification and monitoring. Prospective studies are warranted to establish standardized thresholds and evaluate their prognostic value for disease progression.

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