Glycated CD59 as a Novel Biomarker of Diabetic Nephropathy: Links to Microalbuminuria, Tubular Injury, and Complement Activation

Background: Diabetic nephropathy (DN) is a major complication of type 2 diabetes (T2D). Conventional markers such as microalbuminuria and HbA1c provide limited predictive value. Glycated CD59 (gCD59), a complement-regulatory protein modified under hyperglycaemia, may serve as a novel biomarker. This study evaluated the relationship of gCD59 with renal function, tubular injury, inflammation, endothelial dysfunction, and complement activation in T2D patients. Methods: A total of 320 T2D patients were enrolled and divided equally into groups with and without microalbuminuria (n = 160 each). Laboratory parameters included HbA1c, estimated glomerular filtration rate (eGFR; creatinine ± cystatin C), and plasma gCD59. Urinary neutrophil gelatinase-associated lipocalin (NGAL) or kidney injury molecule-1 (KIM-1) were measured as tubular injury markers. High-sensitivity C-reactive protein (hs-CRP), soluble ICAM-1/VCAM-1, apolipoprotein B (ApoB), and soluble membrane attack complex (sMAC, C5b-9) were assessed. Data on reno-protective medications (ACEi/ARB, SGLT2i) were recorded. Correlation and multivariate regression analyses were performed. Results: Compared with patients without microalbuminuria, those with microalbuminuria showed higher gCD59, HbA1c, urinary NGAL/KIM-1, hs-CRP, ApoB, sICAM-1/VCAM-1, and sMAC levels (all p < 0.01). Mean eGFR was significantly lower in the microalbuminuria group (p < 0.001). gCD59 correlated positively with sMAC (r = 0.62, p < 0.001), urinary NGAL/KIM-1 (r = 0.58, p < 0.001), and HbA1c (r = 0.55, p < 0.001). In multivariate regression, gCD59, urinary NGAL/KIM-1, and sMAC emerged as independent predictors of microalbuminuria after adjustment for HbA1c, lipid profile, and medication use. Use of ACEi/ARB and SGLT2i was associated with lower biomarker levels and better renal function. Conclusions: gCD59 is closely linked with microalbuminuria, tubular injury, endothelial dysfunction, and complement activation in T2D. Its integration with conventional and novel biomarkers may improve early detection and risk stratification of DN, supporting more targeted interventions.