Podocyte Infolding Glomerulopathy: A Special Morphology of Podocyte Injury Caused by Heterogeneous Diseases
Hong Ling, Lin Wang, Honglei Wang, Qihua Wang, Shicong Yang, Tian Tian, Tianjiao Cui, Shuling Yue, Xiaotao Hou, Zhihua Zheng, Wenfang Chen
Abstract
BackgroundPodocyte infolding glomerulopathy (PIG) is a newly recognized rare glomerular injury. The clinical significance and mechanism of this injury pattern remains unclear.MethodsWe conducted a retrospective study of renal biopsies from January 2018 to December 2020 in Kingmed Diagnostics. The renal biopsy features and clinical data were reviewed. Laser scanning microdissection and mass spectrometry (LMD/MS) was conducted to analyze the potential mechanism.ResultsTotally 116 (0.92‰) out of 126,086 biopsies were diagnosed as PIG during the period. 89 (76.7%) cases were found to have PIG coexisting with immune-complex associated glomerulonephritis (IC-PIG) while 27 (23.3%) were identified as isolated PIG without immunoglobulin or complement deposition. Systemic lupus erythematosus (SLE) especially with membranous lupus nephritis, was diagnosed in most (70.8%) IC-PIG cases. 51.9% of the isolated PIG had no known underlying conditions, yet a relatively high positive rate (42.1%) of antinuclear antibody (ANA) was detected. Nearly half (47.5%) of the patients presented with nephrotic syndrome. PIG grade was associated with proteinuria in isolated PIG (P=0.035). LMD/MS revealed dysregulated cytoskeletal protein α-actinin4 (ACTN4) and Tubulin Beta-4 Chain (TUBB4A) in PIG compared with normal donor kidney and minimal change disease (MCD). The displacement of ACTN4 into the glomerular basement membrane (GBM) was confirmed by the confocal microscope.ConclusionPIG is a rare podocyte injury that can exist alone without underlying disease or be concurrent with various diseases, especially SLE. Podocyte cytoskeletal protein ACTN4 and TUBB4A were dysregulated which may be involved in the mechanism of PIG.