Proposal of podocytic infolding glomerulopathy as a new disease entity: a review of 25 cases from nationwide research in Japan
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A rare and peculiar glomerulopathy has begun to be recognized in Japan. The Japanese Society of Nephrology has established a research working group and has collected cases from all over Japan in an attempt to understand the complete spectrum of this glomerulopathy.
The diagnostic criterion, which was needed to collect the cases, was proposed as a glomerulopathy showing microspheres or microtubular structures or both associated with podocytic infolding into the glomerular basement membrane (GBM) on electron microscopy. The lesion shows a non-argentaffin hole in the GBM with periodic acid methenamine silver staining and is similar to membranous glomerulonephritis.
Twenty-five cases were collected from 17 institutions. Patients were 20–69 years old (19 women, 6 men). Seventeen patients also had collagen diseases such as lupus nephritis and Sjögren’s syndrome. All patients had proteinuria. Proteinuria showed a remission in 15 of 23 patients within 12 months, but proteinuria remained higher than 1.0 g/day in five patients despite different types of therapy. Podocytic infolding including microspheres showed either positive or negative staining for immunoglobulins. Cluster formation of microspheres was found in 4 of 17 patients with collagen disease, and in five out eight patients without collagen disease. Electron-dense deposits in the GBM were also found in 6 of 17 patients with collagen disease but were not found in eight patients without collagen disease.
Some patients might have a subtype of lupus nephritis, class V, or membranous glomerulonephritis. However, we propose a new disease entity, podocytic infolding glomerulopathy, as a common basis of all 25 patients, because we suspect that microspheres or microtubular structures or both can be derived from podocytic infolding.
KeywordsRenal biopsy Glomerulonephritis Podocytic infolding Electron microscopy Microspheres
- 1.Word Health Organization. Section 1. Classification of Glomerular Diseases. Glossary of Terms. In: Churg J, Bernstein J, Glassock RJ, editors. Renal disease classification and atlas of glomerular diseases. 2nd ed. Tokyo: Igaku-Shoin; 1995. p. 3–26.Google Scholar
- 3.Sugiyama H, Maruyama M, Morinaga H, Inoue T, Takiue K, Kikumoto Y, et al. Unique microstructures and podocytic infolding in glomerular basement membrane associated with collagen diseases: a report of three cases.Clin Exp Nephrol. 2008, doi: 10.1007/s10157-008-0098-6.
- 4.Sato M, Kogure T, Kanemitsu M. A case of systemic lupus erythematosus showing invagination of the podocyte into the glomerular basement membrane: an electron microscopic observation of a repeated-renal biopsy. Clin Exp Nephrol. 2008, doi: 10.1007/s10157-008-0091-0.
- 5.Kitazawa K, Joh K, Akizawa T. A case of lupus nephritis coexisting with podocytic infolding associated with Takayasu’s arteritis. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0094-x.
- 6.Jinguuji Y, Nukui I, Wakasugi M, Yamashita H. Two cases of systemic lupus erythematosus complicated by hydronephrosis and unique small structures observed in the glomerular basement membrane. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0092-z.
- 7.Fujigaki Y, Muranaka Y, Sakakima M, Ohta I, Sakao Y, Fujikura T, et al. Analysis of intra-GBM microstructures in a SLE case with glomerulopathy associated with podocytic infolding. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0095-9.
- 8.Miura N, Mori Y, Yoshino M, Suga N, Kitagawa W, Yamada H, et al. Membranous nephropathy (bubbling appearance and spike formation) without immunoglobulin deposition in a patient with systemic lupus erythematosus. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0096-8.
- 9.Mii A, Shimizu A, Masuda Y, Ishizaki M, Sato S, Hara K, et al. A case of lupus nephritis with diffuse podocytic infolding 5 into the glomerular basement membrane. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0097-7.
- 10.Tanaka M, Watanabe K, Asahi K, Katoh T, Watanabe T. Lupus nephritis with podocytic infolding and intramembranous microstructures. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0090-1.
- 11.Koike K, Utsunomiya Y, Ito Y, Tokudome S, Miyazaki Y, Suzuki T, et al. A case of glomerulopathy showing podocytic infolding in association with Sjo¨gren’s syndrome and primary biliary cirrhosis. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0093-y.
- 12.Matsuo T, Kobayashi Y, Nemoto N, Sano T, Kamata K, Shigematsu H. A nephrotic case of vesicoureteral reflux representing focal segmental glomerulosclerosis associated with podocytic infolding lesions. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0086-x.
- 13.Arifa N, Nakashima Y, Yan Z, Le VT, Taguchi T, Nishioka K, et al. Unusual glomerulopathy with atypical thickening of glomerular basement membrane and intramembranous microparticles. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0103-0.
- 14.Inoue Y, Kanda Y, Kinoshita C, Kanda C. Intramembranous microspherical structures in focal segmental glomerulosclerosis:a case report. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0101-2.
- 15.Yamada S, Masutani K, Katafuchi R, Fujigaki Y, Muranaka Y, Tsuruya K, et al. Focal segmental glomerulosclerosis with intramembranous vesicle-like microstructures and podocytic infolding lesion. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0088-8.
- 16.Nomura S, Inoue-Kiyohara M, Oosugi K, Ishikawa E, Obe T, Horiki T, et al. Unusual glomerulopathy with aggregated subepithelial microspheric particles resembling membranous nephropathy: a variant of glomerulopathy associated with podocytic infolding? Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0089-7.
- 17.Nishi S, Imai N, Saito T, Ueno M, Arakawa M, Oota T, et al. A nephropathy presenting the microparticles in the glomerular basement membrane in a patient of hepatitis B viral infection. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0087-9.
- 18.Yoshimura K, Joh K, Kitamura H, Takahashi Y, Yokote S, Kasai K, et al. A case report of glomerulopathy-associated podocytic infolding 5 in a patient with tumor lysis syndrome. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0099-5.
- 19.Masuda Y, Mii A, Shimizu A, Fujita E, Aki K, Ishikawa K, et al. Invagination and infolding of podocytes in glomerular basement membrane in the cases of primary membranous nephropathy. Clin Exp Nephrol. 2008. doi: 10.1007/s10157-008-0100-3.
- 20.Fujigaki Y, Kobayashi S, Nagase M, Honda N, Otawara Y, Tajima A, et al. Indentation of the glomerular basement membrane in cases with minor abnormalities. J Clin Microscopy. 1987;20:5–6.Google Scholar
- 21.Schwartz MM. Membranous glomerulonephritis. In: Jeannette JC, Olson JL, Schwartz MM, Silva FG, editors. Heptinstall’s Pathology of the Kidney. 6th ed. Philadelphia: Lippincott/Williams &Wilkins; 2007. p. 205–51.Google Scholar
- 22.D’Agati, Jennette JC, Silva FG. 7. Membranous glomerulopathy. In: King DW, editor. Atlas of Nontumor Pathology. 1st Series, Fascicle 4. Non-Neoplastic Kidney Diseases. American Registry of pathology, Armed Forces Institute of Pathology. Silver Spring: ARP Press; 2005. pp 161–188.Google Scholar
- 23.Venkataseshan VS, Lieberman K, Kim DU, Thung SN, Dikman S, D’Agati V, et al. Hepatitis-B-associated glomerulonephritis: pathology, pathogenesis, and clinical course. Medicine (Baltimore). 1990;69:200–16.Google Scholar
- 25.Debiec H, Guigonis V, Mougenot B, Haymann J-P, Bensman A, Deschenes G, et al. Antenatal membranous glomerulonephritis with vascular injury induced by anti-neutral endopeptidase antibodies: toward new concepts in the pathogenesis of glomerular diseases. Am Soc Nephrol. 2003;14:27–32.CrossRefGoogle Scholar