Peroxidasin expression patterns predict fibrosis and kidney function decline in IgA nephropathy

Peroxidasin (PXDN), a heme-containing peroxidase involved in basement membrane assembly, has been increasingly implicated in fibrotic processes, yet its role in kidney disease remains unclear. We therefore characterized PXDN expression in kidney biopsies from patients with IgA nephropathy (IgAN), a leading cause of CKD, and assessed its association with fibrosis. Immunofluorescence demonstrated widespread PXDN expression across renal compartments, with predominant localization in distal tubules, consistent with healthy tissue. In contrast, PXDN expression was reduced in proximal tubules, including non-atrophic segments, and markedly increased in the fibrotic interstitium. PXDN strongly correlated with collagen III deposition in sclerotic glomeruli and fibrotic interstitium, but not with collagen IV. Clinically, patients with impaired kidney function (eGFR < 60 ml/min/1.73 m²) exhibited higher PXDN expression in glomeruli, proximal tubules, and fibrotic interstitium, with glomerular PXDN inversely correlating with eGFR. These findings reveal compartment-specific alterations in PXDN expression in IgAN, associated with interstitial fibrosis, collagen III deposition, and declining kidney function. PXDN may participate in fibrotic remodeling processes and represents a potential therapeutic target, warranting further investigation in CKD progression.