Morphological analysis of podocyte injury and death in primary IgA nephropathy

Abstract

Introduction: IgA nephropathy (IgAN) is characterized by hematuria but can present with different clinical presentations. Proteinuria has been reported as the most important risk factor for the progression of IgAN and it may be related to podocyte injury. Methods: The kidney biopsy samples from patients with IgAN were analyzed using immunohistochemistry for WT1 to determine podocyte density and transmission electron microscopy to assess ultrastructural changes in podocytes and adjacent structures. A comparative group of patients diagnosed with minimal change disease (MCD) and a control group of autopsy samples without kidney disease were included. Results: Slit diaphragm density was lower in IgAN cases compared to controls but higher than in MCD cases. Podocyte density was significantly lower in the IgAN and MCD groups compared to controls, with the MCD group showing even lower density than the IgAN group. Podocyte density was lower in cases with nephrotic proteinuria both in MCD and IgAN. A significant negative correlation was detected between podocyte density and proteinuria in both conditions. A significantly lower proportion of detached podocytes was observed in cases with isolated autophagy and cases with autophagy showed a lower frequency of hematuria and a higher percentage of T0. Conclusion: We demonstrated that podocyte alterations in IgAN correlate with clinical parameters, including nephrotic proteinuria, hematuria, and interstitial fibrosis. Podocyte loss was associated with necrosis and mitotic catastrophe, while autophagy was prevalent but not apoptosis. Autophagy appears to protect against podocyte detachment. These findings highlight pathophysiological mechanisms relevant to diagnostic and clinical practice.