Correlation between podocyte foot process effacement and proteinuria in human glomerular diseases

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Article Title:	Correlation between podocyte foot process effacement and proteinuria in human glomerular diseases
Authors:	Silvia Spânu, Constantin Crăciun, Costel Spânu, Mirela Gherman-Căprioară
Affiliation:	1 University of Medicine and Pharmacy “I.Haţieganu” , Department of Nephrology, Cluj-Napoca, Romania 2 University “Babeş – Bolyai” , Electron Microscopy Center, Cluj-Napoca, Romania
Abstract:	The podocyte is a specialized epithelial cell with numerous interdigitating foot processes which play an important role in the regulation of the glomerular basement membrane (GBM) permeability. The nephrotic syndrome results from increased glomerular permeability to proteins and is structurally belived to be associated with podocyte foot process effacement. Despite increasing knowledge of the molecular composition of the glomerular filtration barrier, the relationship between proteinuria and foot process effacement remains unclear. The aim of this study is to analyze the relationship between podocyte foot process effacement and the level of proteinuria. Morphometric analysis was performed on electron microscopy images taken randomly from 37 patients diagnosed with various glomerular diseases. 17 of the patients had nephrotic syndrome and 20 had subnephrotic proteinuria. The mean foot process width (FPW) was quantitated for each patient and for each group and correlated with the level of proteinuria. In the non nephrotic group segmental effacement of the foot processes was present and the mean FPW was 422 ± 90 nm. In the nephrotic group the foot processes were diffusely effaced, reflected by a FPW of 1196 ± 517 nm, significantly larger than in the subnephrotic group. The level of proteinuria correlated with the FPW only when all 37 patients were analyzed together. There was no correlation when the groups were studied separately. The mean FPW was significantly larger in the nephrotic group compared to the non nephrotic group. Podocyte foot process effacement correlated with proteinuria.
Keywords:	podocyte, foot process effacement, foot process width, proteinuria
References:	Assmann KJ, van Son JP, Dijkman HB, Koene RA (1992) A nephritogenic rat monoclonal antibody to mouse aminopeptidase A. Induction of massive albuminuria after a single intravenous injection. J Exp Med , 175: 623-635. Bertani T, Poggi A, Pozzoni R, et al (1982) Adriamycininduced nephrotic syndrome in rats: Sequence of pathologic events. Lab Invest, 46:16-23. Bonsib SM. (2007) Renal anatomy and histology. In: Jennette JC, ed. Heptinstall’s Pathology of the Kidney. Philadelphia: Lippincott Williams & Wilkins, 25-32. Branten AJ, van den Born J, Jansen JL, et al (2001) Familial nephropathy differing from minimal change nephropathy and focal glomerulosclerosis. Kidney Int, 59: 693-701. D’Agati V.(2003) Pathologic classification of focal segmental glomerulosclerosis. Semin Nephrol, 23: 117-134. Deegens JKJ, Dijkman HBPM, Borm GF, et al (2008) Podocyte foot process effacement as a diagnostic tool in focal segmental glomerulosclerosis. Kidney Int, 74: 1568-1576. Farquhar MG, Vernier RL, Good RA. (1957) An electron microscope study of the glomerulus in nephrosis, glomerulonephritis, and lupus erithematosus. J Exp Med, 106: 649-660. Fries JW, Rumpelt HJ, Thoenes W. (1987) Alterations of glomerular podocytic processes in immunologically mediated glomerular disorders. Kidney Int, 32: 742-748. Gundersen HJ, Seefeldt T, Osterby R. (1980) Glomerular epithelial foot processes in normal man and rats: distribution of true width and its intra- and interidividual variation. Cell Tissue Res, 205: 147-155. Heymann W, Hachtel DB, Harwood S et al (1959) Production of nephrotic syndrome in rats by Freunds adjuvant in rat kidneys. Proc Soc Exp Biol Med, 100: 660-664. Kaplan BS, Renaud L, Drummond KN. (1976) Effect of aminonucleoside, daunomycin, and adriamycin on carbon oxidation by glomeruli. Lab Invest, 34: 174-278. Kerjaschki D.(1994) Dysfunctions of cell biological mechanisms of visceral epithelial cell (podocytes) in glomerular diseases. Kidney Int, 45: 300-313. Kerjaschki D, Schulze M, Binder S et al (1989) Transcellular transport and membrane insertion of the C5b-9 membrane attack complex of complement by glomerular epithelial cells in experimental membranous nephropathy. J Immunol, 143: 546-552. Liu G, Kaw B, Kurfis J, et al (2003) Neph1 and nephrin interaction in the slit diafragm is an importsnt determinant of glomerular permeability. J Clin Invest, 112: 209-221. Matsui K, Breiteneder-Gelef S, Kerjaschki D. (1998) Epitope-specific antibodies to the 43-kD glomerular membrane protein podoplanin cause proteinuria and rapid flattening of podocytes. J Am Soc Nephrol, 9: 2013-2026. Michael AF, Blau E, Vernier RL. (1970) Glomerular polyanion. Alteration in aminonucleoside nephrosis. Lab Invest, 23: 649-657. Orikasa M, Matsui K, Oite T, Shimitsu F. (1988) Massive proteinuria induced in rats by a single intravenous injection of a monoclonal antibody. J Immunol, 141: 807-814. Patalunan M, Miller P, Jumping-Eagle S et al (1997) Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest, 99: 342-348. Pavenstadt H, Kriz W, Kretzler M. (2003) Cell biology of the glomerular podocyte. Physiol Rev, 83:253-307. Ryan GB, Karnovski MJ. (1957) An ultrastructural study of the mechanisms of proteinuria in aminonucleoside nephrosis. Kidney Int, 8: 219-232. Powell HR. (1976) Relationship between proteinuria and epithelial cell changes in minimal lesion glomerulopathy. Nephron, 16: 310-317. Song YC, Dae EC, Beom JL. (2010) Morphometric Analysis of Podocyte Foot Process Effacement in IgA Nephropathy and Its Associacion with Proteinuria. Ultrastruct Pathol, 34: 195-198. van den Berg JC, van den Berg Weerman MA, Assmann KJ et al (2004) Podocyte foot process effacement is not correlated with the level of proteinuria in human glomerulopathies. Kidney Int, 66: 1901-1906.
*Correspondence:	Silvia Spânu, University of Medicine and Pharmacy “I.Haţieganu”, Department of Nephrology, Cluj-Napoca, Clinicilor St., no. 3-5, 400006, Cluj-Napoca, Romania, Tel. +40745192191, email: silvia_spanu@yahoo.com