Urinary glypican-5 concentration as an early associated biomarker for diabetic nephropathy

Abstract

Objective: Early diagnosis of diabetic nephropathy (DN) is limited by the low sensitivity of albuminuria and estimated glomerular filtration rate (eGFR). Urinary glypican‑5 (GPC5), a podocyte heparan sulfate proteoglycan, is a candidate biomarker. This cross‑sectional study evaluated the association between urinary GPC5 and DN severity in type 2 diabetes mellitus (T2DM).

Methods: We enrolled 100 Iraqi T2DM patients (65 male, 35 female; mean age 58.3 years) and 50 healthy controls (32 male, 18 female; mean age 54.6 years). Fasting blood glucose, HbA1c, urine albumin‑to‑creatinine ratio (UACR), eGFR (CKD‑EPI), and urinary GPC5 (ELISA) were measured. Patients were stratified by albuminuria (normo‑/micro‑/macro‑albuminuria) and eGFR stages (G1–G4). Analyses used t‑tests, ANOVA with Tukey post‑hoc, and Pearson correlation.

Results: Urinary GPC5 was higher in patients than controls (1.97±0.45 vs. 1.17±0.25 ng/mL, p<0.001). GPC5 was already elevated in normoalbuminuric patients (1.62±0.32 ng/mL) and increased across micro-albuminuric (1.92±0.36) and macroalbuminuric (2.32±0.40) groups (p<0.001 for trend). Similarly, GPC5 rose with declining eGFR: normal (1.54±0.30), mild (1.84±0.28), moderate (1.98±0.35), severe (2.27±0.43 ng/mL; all p<0.001 vs. controls). GPC5 correlated positively with HbA1c (r=0.68, p<0.001) and negatively with eGFR (r=−0.76, p<0.001).

Conclusions: Urinary GPC5 is strongly associated with DN presence and severity, including in normoalbuminuric patients. These findings support further evaluation of GPC5 as an early diagnostic biomarker, but prospective validation is needed.