Infolding Glomerulopathy

Podocyte infolding glomerulopathy (PIG) is a condition first described in 2008. It has been mainly described in Japanese literature and usually presents as subnephrotic proteinuria, although nephrotic syndrome occurs in approximately a third of patients. It is characterized on renal biopsy by infolding or protrusion of podocyte cytoplasm into the glomerular basement membrane, as well as intramembranous microspherules or microtubules, evidenced by electron microscopy (Ting JA, et al. Podocyte Infolding Glomerulopathy, First Case Report From North America. Can J Kidney Health Dis. 2021;8:20543581211048357. [PubMed link]).

PIG is an alteration of uncertain origin that is commonly associated with autoimmune diseases. Its specific treatment and clinical course are unknown. To date few cases have been reported, mainly in patients of Asian origin. In general, the condition is reported in young patients, with a higher prevalence in females. On light microscopy there is thickening of capillary walls with small non-argyrophilic intramembranous bubbles similar to those found in membranous glomerulonephritis, but no deposits of electron-dense material are seen in the ultrastructure; instead, it is observed the presence of translucent microspheres generated by infolding of the podocytic cytoplasm in the basement membranes (Malvar A, et al. Podocyte infolding glomerulopathy; report of the first case in Latin America and review of the literature. Nefrologia (Engl Ed). 2020;40(4):469-473. [PubMed link]).

The largest series, published by Joh et al. with 25 cases in Japan in 2008, showed that 17 of these patients also had collagen diseases such as SLE or Sjögren's syndrome. There are also reports of isolated cases of PIG in patients with multiple myeloma, primary biliary cholangitis, tumour lysis syndrome, Takayasu's arteritis, hepatitis B, vesicoureteral reflux and even cases associated with anaerobic infections. It is also associated with patterns of membranous glomerulopathy and focal segmental sclerosis. This could indicate that PIG is a result of a non-specific podocyte injury (Malvar A, et al. Podocyte infolding glomerulopathy; report of the first case in Latin America and review of the literature. Nefrologia (Engl Ed). 2020;40(4):469-473. [PubMed link]).

In the original first descrption and proposal of PIG as a new disease entity, the authors suggest dividing it into three types: type A with only primary podocytic infolding, type B with both primary podocytic infolding and microstructures in the GBM, and type C with only microstructures in the GBM. From the immunopathological point of view, it has also been proposed to divide PIG into two: PIG without immune complexes and PIG associated to immunocomplexes glomerular disease, i.e. PIG in lupus nephritis, membranous GN (primary or secondary), and perhaps others (Ting JA, et al. Podocyte Infolding Glomerulopathy, First Case Report From North America. Can J Kidney Health Dis. 2021;8:20543581211048357. [PubMed link]).

Pandit AP, Rennke HG, Denker BM. Podocytic Infolding Glomerulopathy in a Patient with Phospholipase A2 Receptor-Positive Membranous Nephropathy and Review of the Literature. Nephron. 2021;145(5):496-502. [PubMed link]
Ting JA, Hung W, McRae SA, Barbour SJ, Copland M, Riazy M. Podocyte Infolding Glomerulopathy, First Case Report From North America. Can J Kidney Health Dis. 2021;8:20543581211048357. [PubMed link]
Malvar A, Davila P, Ferrari M, Delgado P, Iscoff P, Lococo B, Alberton V. Podocyte infolding glomerulopathy; report of the first case in Latin America and review of the literature. Nefrologia (Engl Ed). 2020;40(4):469-473. [PubMed link]
Zhang T, Sun W, Xue J, Chen J, Jiang Q, Mou L, Du H. Podocytic infolding glomerulopathy: two new cases with connective tissue disease and literature review. Clin Rheumatol. 2019;38(5):1521-1528. [PubMed link]
Kwon KW, Jeong HJ, Lee JH. Podocytic infolding glomerulopathy: A case report. Ultrastruct Pathol. 2016;40(6):374-377. [PubMed link]
Joh K, Taguchi T, Shigematsu H, Kobayashi Y, Sato H, Nishi S, Katafuchi R, Nomura S, Fujigaki Y, Utsunomiya Y, Sugiyama H, Saito T, Makino H. 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(6):421-31. [PubMed link]