Oxidative Stress-Induced Expression Levels of PXDN and NF-κB in Type 2 Diabetic Patients With Nephropathy

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in patients with diabetes mellitus (DM). Early detection remains difficult, but essential for timely management. In this study, we assessed Peroxidasin (PXDN) gene expression as a biomarker for early detection of DN and for reflection of oxidative stress status. We also compared PXDN and Nuclear factor-κB (NF-κB) expression levels in DN patients, aiming to identify a reliable diagnostic biomarker.

This prospective cross-sectional study included 40 patients with T2DM with and without nephropathy, and 20 matched healthy controls. PXDN mRNA expression was quantified by real-time polymerase chain reaction (qRT-PCR). Biochemical analyses of malondialdehyde (MDA) and total antioxidant capacity (TAC) were also done to assess the oxidative stress status. Laboratory parameters, including glycated haemoglobin, urinary albumin-to-creatinine ratio, estimated glomerular filtration rate, and microalbuminuria, were measured and correlated with gene expression levels and the oxidative stress status.

PXDN mRNA expression was significantly upregulated in patients with DN compared to diabetic cases without nephropathy and control subjects. MDA levels were significantly elevated in both diabetic groups relative to controls, but no significant difference was found between DN and DM without renal impairment. TAC was significantly lower in DN cases compared to DM and controls. The NF-κB gene was upregulated in both diabetic groups compared to control subjects, but no significant difference was found between DN and DM without nephropathy. Furthermore, PXDN expression did not correlate with MDA, TAC, or NF-κB levels. Receiver operating characteristic (ROC) analysis identified PXDN as a highly specific and sensitive marker for DN, outperforming conventional oxidative stress biomarkers in distinguishing DN from both diabetic and healthy individuals.

PXDN is significantly upregulated in DN and may serve as a sensitive and specific molecular marker for early detection of nephropathy compared to NF-κB.