Morphological subtypes and clinicopathological features of podocyte infolding glomerulopathy: retrospective nationwide Japanese cohort study of 93 cases.

BACKGROUND: Podocyte infolding glomerulopathy (PIG) is a rare glomerular disease, with case reports and cohort studies lacking clear morphological diagnostic criteria. We aimed to establish transmission electron microscopy (TEM)-based diagnostic criteria for PIG and classify its morphological subtypes. METHODS: This retrospective nationwide cohort study was conducted by the PIG Working Group of the Japanese Society of Nephrology. Clinical data and TEM findings were collected from patients diagnosed with or suspected of PIG at 69 institutions across Japan between 1991-2025. PIG was defined by TEM as podocyte infolding exceeding half the glomerular basement membrane (GBM) thickness at two or more sites within a single capillary loop or the presence of microspheres or microtubules within the GBM. Cases were classified into morphological subtypes, and their clinical characteristics were analyzed. RESULTS: Among 103 registered cases, 93 met diagnostic criteria. Four morphological subtypes were identified: Type A, primary podocyte infolding without prominent microspheres or microtubules (n = 21); Type B, predominant microspheres (n = 34); Type C, microtubules with or without microspheres (n = 38); and Type D, dense clusters of microspheres (n = 10). Types B and C were more common in younger females and frequently associated with systemic lupus erythematosus (58% and 71%, respectively), whereas Types A and D occurred mainly in older males and were not associated with SLE. CONCLUSIONS: We established TEM-based diagnostic criteria for PIG and identified four morphological subtypes, suggesting two clinicopathological phenotypes: SLE-associated (B and C) and non-SLE-associated (A and D).