A Case of Developing Podocyte Infolding Glomerulopathy–Like Features and Endothelial Changes Associated With an Immune-Mediated Mechanism

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We report the case of a 75-year-old man with proteinuria whose initial renal biopsy, performed at the age of 71, demonstrated only minor abnormalities, including partial podocyte foot process effacement without significant immune deposits, findings suggestive of podocyte injury. Four years later, at the age of 75, and in the absence of immunosuppressive therapy, a repeat biopsy performed after the onset of nephrotic syndrome revealed podocyte infolding associated with focal glomerular basement membrane (GBM) microspheres and endothelial alterations. The spherical structures appeared to originate directly from podocytes or from invaginated podocyte cytoplasm and were subsequently distributed within the GBM. Although immunostaining demonstrated immune deposition along the glomerular capillary walls, corresponding electron-dense deposits were not identified ultrastructurally. These findings do not support a conventional immune complex–mediated process but instead suggest possible humoral involvement. The coexistence of podocyte injury and suspected humoral mechanisms, together with podocyte infolding, endothelial alterations, and putative podocyte-derived spheres, may provide important pathological insight into the development of podocyte infolding glomerulopathy-like features.