Glomerular Proteinuria: a Complex Interplay Between Unique Players

Overview

Journal Adv Chronic Kidney Dis

Specialty Nephrology

Date 2011 Jul 26

PMID 21782129

Citations 17

Authors

Puneet Garg

Ton Rabelink

Affiliations

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Abstract

Protein leak in the urine is a harbinger of disruption of the glomerular filtration barrier. It also correlates with disease progression and development of ESRD. At present, therapies are aimed at decreasing proteinuria to decrease further damage to the filter and as a marker of remission. Understanding the mechanism of molecular events that lead to protein leak is vital to developing new therapeutic interventions. There has been tremendous progress over the last decade in identifying gene defects which result in hereditary proteinuric defects. This has led to identifying pathways by which these genes regulate the structure and function of the components of the filtration barrier, namely the podocytes, mesangial cells, endothelial cells, and the basement membrane. Using gene knockout mouse models, a role of tubular cells in regulating proteinuria is also emerging. In this review, we have attempted to present some of the prevailing understanding of the underlying mechanisms and physiology of proteinuria.

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References

Kalluri R . Proteinuria with and without renal glomerular podocyte effacement. J Am Soc Nephrol. 2006; 17(9):2383-9. DOI: 10.1681/ASN.2006060628. View

Winn M, Daskalakis N, Spurney R, Middleton J . Unexpected role of TRPC6 channel in familial nephrotic syndrome: does it have clinical implications?. J Am Soc Nephrol. 2006; 17(2):378-87. DOI: 10.1681/ASN.2005090962. View

Wiggins J, Goyal M, Sanden S, Wharram B, Shedden K, Misek D . Podocyte hypertrophy, "adaptation," and "decompensation" associated with glomerular enlargement and glomerulosclerosis in the aging rat: prevention by calorie restriction. J Am Soc Nephrol. 2005; 16(10):2953-66. DOI: 10.1681/ASN.2005050488. View

El-Aouni C, Herbach N, Blattner S, Henger A, Rastaldi M, Jarad G . Podocyte-specific deletion of integrin-linked kinase results in severe glomerular basement membrane alterations and progressive glomerulosclerosis. J Am Soc Nephrol. 2006; 17(5):1334-44. DOI: 10.1681/ASN.2005090921. View

Jarad G, Cunningham J, Shaw A, Miner J . Proteinuria precedes podocyte abnormalities inLamb2-/- mice, implicating the glomerular basement membrane as an albumin barrier. J Clin Invest. 2006; 116(8):2272-9. PMC: 1523402. DOI: 10.1172/JCI28414. View

Pozzi A, Jarad G, Moeckel G, Coffa S, Zhang X, Gewin L . Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity. Dev Biol. 2008; 316(2):288-301. PMC: 2396524. DOI: 10.1016/j.ydbio.2008.01.022. View

Singh A, Friden V, Dasgupta I, Foster R, Welsh G, Tooke J . High glucose causes dysfunction of the human glomerular endothelial glycocalyx. Am J Physiol Renal Physiol. 2010; 300(1):F40-8. PMC: 3023224. DOI: 10.1152/ajprenal.00103.2010. View

Kreisberg J, Karnovsky M . Focal glomerular sclerosis in the fawn-hooded rat. Am J Pathol. 1978; 92(3):637-52. PMC: 2018261. View

Scaplehorn N, Holmstrom A, Moreau V, Frischknecht F, Reckmann I, Way M . Grb2 and Nck act cooperatively to promote actin-based motility of vaccinia virus. Curr Biol. 2002; 12(9):740-5. DOI: 10.1016/s0960-9822(02)00812-6. View

10.

Yamamoto Y, Kato I, Doi T, Yonekura H, Ohashi S, Takeuchi M . Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. J Clin Invest. 2001; 108(2):261-8. PMC: 203021. DOI: 10.1172/JCI11771. View

11.

Khoshnoodi J, Sigmundsson K, Ofverstedt L, Skoglund U, Obrink B, Wartiovaara J . Nephrin promotes cell-cell adhesion through homophilic interactions. Am J Pathol. 2003; 163(6):2337-46. PMC: 1892394. DOI: 10.1016/S0002-9440(10)63590-0. View

12.

Ciani L, Patel A, Allen N, ffrench-Constant C . Mice lacking the giant protocadherin mFAT1 exhibit renal slit junction abnormalities and a partially penetrant cyclopia and anophthalmia phenotype. Mol Cell Biol. 2003; 23(10):3575-82. PMC: 164754. DOI: 10.1128/MCB.23.10.3575-3582.2003. View

13.

Huber T, Kwoh C, Wu H, Asanuma K, Godel M, Hartleben B . Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. J Clin Invest. 2006; 116(5):1337-45. PMC: 1440708. DOI: 10.1172/JCI27400. View

14.

Ashworth S, Teng B, Kaufeld J, Miller E, Tossidou I, Englert C . Cofilin-1 inactivation leads to proteinuria--studies in zebrafish, mice and humans. PLoS One. 2010; 5(9):e12626. PMC: 2935884. DOI: 10.1371/journal.pone.0012626. View

15.

Kang Y, Li Y, Dai C, Kiss L, Wu C, Liu Y . Inhibition of integrin-linked kinase blocks podocyte epithelial-mesenchymal transition and ameliorates proteinuria. Kidney Int. 2010; 78(4):363-73. PMC: 3065782. DOI: 10.1038/ki.2010.137. View

16.

Dressler G, Woolf A . Pax2 in development and renal disease. Int J Dev Biol. 1999; 43(5):463-8. View

17.

Wharram B, Goyal M, Wiggins J, Sanden S, Hussain S, Filipiak W . Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol. 2005; 16(10):2941-52. DOI: 10.1681/ASN.2005010055. View

18.

Brown E, Schlondorff J, Becker D, Tsukaguchi H, Tonna S, Uscinski A . Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. Nat Genet. 2009; 42(1):72-6. PMC: 2980844. DOI: 10.1038/ng.505. View

19.

Srichai M, Konieczkowski M, Padiyar A, Konieczkowski D, Mukherjee A, Hayden P . A WT1 co-regulator controls podocyte phenotype by shuttling between adhesion structures and nucleus. J Biol Chem. 2004; 279(14):14398-408. DOI: 10.1074/jbc.M314155200. View

20.

Scaglia F, Vogel H, Hawkins E, Vladutiu G, Liu L, Wong L . Novel homoplasmic mutation in the mitochondrial tRNATyr gene associated with atypical mitochondrial cytopathy presenting with focal segmental glomerulosclerosis. Am J Med Genet A. 2003; 123A(2):172-8. DOI: 10.1002/ajmg.a.20315. View