Cell invasion in glomerular basement membrane: infolding glomerulopathy

We describe the case of a 35-year-old woman with Sjogren’s syndrome and scleroderma for several years who was not receiving immunosuppressive therapy. Her urinary protein turned positive with a progressive reduction in complement levels and positive anti-DNA antibodies. Kidney biopsy indicated mild mesangial proliferation with focal glomerular basement membrane (GBM) thickening and lucencies (Supplementary Figure S1, part 1). Immunofluorescent staining revealed mesangial Ig and complement deposition of a full house pattern with faint peripheral capillary IgG deposition (Supplementary Figure S1, parts 2 and 3). Mesangial electron-dense deposition with scarce subepithelial electron-dense deposition and tubuloreticular inclusion was observed by electron microscopy analysis. Because of serological and pathological findings, the patient was diagnosed with lupus nephritis International Society of Neuphrology/Renal Pathology Society class II. However, GBM was thickened with irregularities and numerous intra-GBM microstructures (Figures 1 and 2; Supplementary Figure S2). The findings were consistent with podocyte infolding glomerulopathy. Podocyte infolding glomerulopathy, a rare and unique histological finding that was first reported from Japan 1 Joh K. Taguchi T. Shigematsu H. et al. Proposal of podocytic infolding glomerulopathy as a new disease entity: a review of 25 cases from nationwide research in Japan. Clin Exp Nephrol. 2008; 12: 421-431 Crossref PubMed Scopus (30) Google Scholar and is now starting to be recognized worldwide, 2 Wostmann F. Muller R.U. Gobel H. et al. Case report: a peculiar glomerulopathy in a patient suffering from nephrotic syndrome. BMC Nephrol. 2019; 20: 326 Crossref PubMed Scopus (8) Google Scholar is characterized by the appearance of numerous microstructures in the GBM. The microstructures are believed to be of invaginated podocyte and/or endothelial cells. 1 Joh K. Taguchi T. Shigematsu H. et al. Proposal of podocytic infolding glomerulopathy as a new disease entity: a review of 25 cases from nationwide research in Japan. Clin Exp Nephrol. 2008; 12: 421-431 Crossref PubMed Scopus (30) Google Scholar In this case, the cells invade into the GBM and appear to connect with each other (Figure 1). Moreover, invaded cells spread their processes into the GBM (Figure 2), which resembles microspherules and microtubules. We further prepared serial ultra-thin tissue sections of 80 nm (Supplementary Figure S3). Serial electron microscopy analysis revealed that the cellular bodies of podocytes invaded the GBM dynamically and spread their processes into it. The endothelial cells also invaded the GBM with surrounding microstructures. Although the mechanism of this cell invasion into GBM remains unclear, in our case study membrane attack complex was positive in GBM (Supplementary Figure S1, parts 4 and 5), suggesting intra-GBM complement activation, which might attract the cells into GBM. However, additional histopathological studies are required to further elucidate this rare and unique histopathological entity. Figure 2Podocytes invade the glomerular basement membrane (GBM) and extend their processes (arrowhead), which might spread through the GBM (original magnification ×12,000). To optimize viewing of this image, please see the online version of this article at www.kidney-international.org. View Large Image Figure Viewer Download Hi-res image