Dysregulation of Niacin-Derived NAD+ Salvage Pathway Markers (CD38, NAMPT, SIRT1) Across Albuminuria Stages in Type 2 Diabetes

<i>Background and Objectives</i>: Diabetic nephropathy (DN) is a major cause of end-stage renal disease, yet its molecular basis remains unclear. Nicotinamide adenine dinucleotide (NAD⁺) metabolism is crucial for energy regulation, redox balance, and inflammation. This study investigated the dysregulation of key NAD⁺ salvage enzymes (CD38, NAMPT, and SIRT1) across albuminuria stages in type 2 diabetes (T2D). <i>Materials and Methods</i>: A cross-sectional study was conducted on 225 participants: healthy controls (n = 45), T2D with normoalbuminuria (n = 60), microalbuminuria (n = 60), and macroalbuminuria (n = 60). Serum CD38, NAMPT, and SIRT1 were measured by ELISA, while CD38 and SIRT1 gene expression in peripheral blood mononuclear cells was analyzed by qPCR. <i>Results</i>: CD38 and NAMPT levels increased progressively with albuminuria, whereas SIRT1 levels declined significantly. CD38 and NAMPT correlated positively with HbA1c, creatinine, and urinary albumin-to-creatinine ratio (UACR), while SIRT1 showed inverse correlations and a positive association with eGFR. Regression analysis identified CD38 and NAMPT as independent positive predictors of albuminuria, and SIRT1 as a negative predictor. ROC analysis revealed strong diagnostic performance for CD38 (AUC = 0.89) and SIRT1 (AUC = 0.88). <i>Conclusions</i>: These findings highlight disrupted NAD⁺ salvage pathways in DN and suggest that restoring NAD⁺ balance, through CD38 inhibition, SIRT1 activation, or NAD⁺ precursor supplementation, may offer promising renoprotective strategies.