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Pediatric Nephrology

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01.10.2007 | Brief Report

Renin-angiotensin axis blockade reduces proteinuria in presymptomatic patients with familial FSGS

verfasst von: Lawrence Copelovitch, Marta Guttenberg, Martin R. Pollak, Bernard S. Kaplan

Erschienen in: Pediatric Nephrology | Ausgabe 10/2007

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Abstract

Familial and genetic forms of focal segmental glomerulosclerosis (FSGS) are associated with six different mutations in genes affecting the podocyte (NPHS2, ACTN4, CD2AP, WT1, TRPC6, and PLCE1). Immunosuppressive agents are often unsuccessful in treating this condition. Data regarding the efficacy of renoprotection through blockage of the renin-angiotensin axis is lacking. We describe three children from two different families with familial FSGS in whom partial to complete remission of proteinuria was attained through early blockade of the renin-angiotensin axis. In addition, there was no deterioration of renal function. We speculate that presymptomatic patients with normal renal function who have genetic or familial FSGS may benefit from early blockade of the renin-angiotensin axis and that this may also prevent progressive renal disease.

Goumenos DS, Tsagalis G, El Nahas AM, Shortland JR, Davlouros P, Vlachojannis JG, Brown CB (2006) Immunosuppressive treatment of idiopathic focal segmental glomerulosclerosis: A five year follow-up study. Nephron Clin Practice 104:c75–c82CrossRef

Deegens JK, Assmann KJ, Steenbergen EJ, Hilbrands LB, Gerlag PG, Jansen JL, Wetzels JF (2005) Idiopathic focal segmental glomerulosclerosis: a favourable prognosis in untreated patients? Neth J Med 63:393–398PubMed

Korbet SM (2003) Angiotensin antagonists and steroids in the treatment of focal segmental glomerulosclerosis. Semin Nephrol 23:219–228CrossRefPubMed

Cattran DC, Rao P (1998) Long-term outcome in children and adults with classic focal segmental glomerulosclerosis. Am J Kidney Dis 32:72–79PubMed

Stirling CM (2006) Focal segmental glomerulosclerosis-Does treatment work? Nephron Clin Pract 104:c83–c84CrossRefPubMed

Fogo AB (2001) Progression and potential regression of glomerulosclerosis. Kidney Int 59:804–819CrossRefPubMed

Adamczak M, Gross ML, Krtil J, Koch A, Tyralla K, Amann K, Ritz E (2003) Reversal of glomerulosclerosis after high dose enalapril treatment in subtotally nephrectomized rats. J Am Soc Nephrol 14:2833–2842CrossRefPubMed

Ma L, Nakamura S, Aldigier JC, Rossini M, Yang H, Liang X, Nakamura I, Marcantoni C, Fogo AB (2005) Regression of glomerulosclerosis with high-dose angiotensin inhibitor is linked to decreases plasminogen activator inhibitor-1. J Am Soc Nephrol 16:966–976CrossRefPubMed

Fogo AB (2006) Can glomerulosclerosis by reversed? Nat Clin Pract Nephrol 2:290–291CrossRefPubMed

10.

Ruf RG, Schultheiss M, Lichtenberger A, Karle SM, Zalewski I, Mucha B, Everding AS, Neuhaus T, Patzer L, Plank C, Haas JP, Ozaltin F, Imm A, Fuchshuber A, Bakkaloglu A, Hildebrant F, Members of the APN study group (2004) Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome. Kidney Int 66: 564–570CrossRefPubMed

11.

Daskalakis N, Winn MP (2005) Focal and segmental glomerulosclerosis: Varying biologic mechanisms underlie a final histologic end point. Semin Nephrol 26:89–94CrossRef

12.

Hinkes B, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nürnberg G, Garg P, Verma R, Chaib H, Hoskins BE, Ashraf S, Becker C, Hennies HC, Goyal M, Wharram BL, Schachter AD, Mudumana S, Drummond I, Kerjaschki D, Waldherr R, Dietrich A, Ozaltin F, Bakkaloglu A, Cleper R, Basel-Vanagaite L, Pohl M, Griebel M, Tsygin AN, Soylu A, Müller D; Sorli CS, Bunney TD, Katan M, Liu J, Attanasio M, O’toole JF, Hasselbacher K, Mucha B, Otto EA, Airik R, Kispert A, Kelley GG, Smrcka AV, Gudermann T, Holzman LB, Nürnberg P, Hildebrandt F (2006) Postional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet 38:1397–1405CrossRefPubMed

13.

Benzing T (2006) Genetic testing comes of age: WT1 mutations in steroid-resistant nephrotic syndrome. Pediatr Res 59:165–166CrossRefPubMed

14.

Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf EM, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkalouglu A, Hildebrant F, The arbeitsgemeinschaft fur padiatrische nephrology (2004) Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 15:722–732CrossRefPubMed

15.

Tsukaguchi H, Sudhakar A, Le TC, Nguyen T, Yao J, Schwimmer JA, Schachter AD, Poch E, Abreu PF, Appel GB, Pereira AB, Kalluri R, Pollak MR (2002) NPHS2 mutations in late-onset focal segmental glomerulosclerosis: R229Q is a common disease-associated allele. J Clin Invest 110:1659–1666CrossRefPubMedPubMedCentral

16.

Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, Daskalakis N, Kwan SY, Ebersviller S, Burchette JL, Pericak-Vance MA, Howell DN, Vance JM, Rosenberg PB (2005) A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 308:1801–1804CrossRefPubMed

17.

Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ, Mathis BJ, Rodrigues-Perez JC, Allen PG, Beggs AH, Pollak MR (2000) Mutations in ACTN4, encoding alpha-actinin, cause familial focal segmental glomerulosclerosis. Nat Genet 24:251–256CrossRefPubMed

18.

Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM (1981) Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol 241:F85–F93PubMed

19.

Hoy WE, Hughson MD, Bertram JF, Douglas-Denton R, Amann K (2005) Nephron number, hypertension, renal disease and renal failure. J Am Soc Nephrol 16:2557–2564CrossRefPubMed

20.

Meyrier A (2005) Treatment of focal segmental glomerulosclerosis. Expert Opin Pharmacother 6:1539–1549CrossRefPubMed

21.

The GISEN Group (1997) Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric non-diabetic nephropathy. Lancet 349:1857–1863CrossRef

22.

Remuzzi A, Puntorieri S, Battaglia C, Bertani T, Remuzzi G (1990) Angiotensin converting enzyme inhibition ameliorates glomerular filtration of macromolecules and water and lessens glomerular injury in the rat. J Clin Invest 85:541–549CrossRefPubMedPubMedCentral

23.

Lapinski R, Perico N, Remuzzi A, Sangalli F, Benigni A, Remuzzi G (1996) Angiotensin II modulates glomerular capillary permselectivity in rat isolated perfused kidney. J Am Soc Nephrol 7:653–660PubMed

24.

Gloy J, Henger A, Fischer KG, Nitschke R, Bleich M, Mundel P, Schollmeyer P, Greger R, Pavenstadt H (1998) Angiotensin II modulates cellular functions of podocytes. Kidney Int 67:S168–S170CrossRef

25.

Macconi D, Abbate M, Morigi M, Angioleti S, Mister M, Buelli S, Bonomelli M, Mundel P, Endlich K, Remuzzi A, Remuzzi G (2006) Permselctive dysfunction of podocyte-podocyte contact upon angiotensin II unravels the molecular target for renoprotective intervention. Am J Pathol 168:1073–1085CrossRefPubMedPubMedCentral

26.

Singh A (2006) Dual blockade of renin-angiotensin system in primary focal segmental glomerulosclerosis. Nephrol Dial Transplant 21:830–831CrossRefPubMed

27.

Remuzzi G, Remuzzi A (2005) Is regression of chronic nephropathies a therapeutic target? J Am Soc Nephrol 16:840–842CrossRefPubMed

28.

Stiles KP, Abbott KC, Welch PG, Yuan CM (2001) Effects of angiotensin-converting enzyme inhibitor and steroid therapy on proteinuria in FSGS: a retrospective study in a single center. Clin Nephrol 56:89–95PubMed

29.

Usta M, Ersoy A, Dilek K, Ozdemir B, Yavuz M, Gullulu M, Yurtkuran (2003) Efficacy of losartan in patients with primary focal segmental glomerulosclerosis resistant to immunosuppressive treatment. J Intern Med 253:329–334CrossRefPubMed

30.

Mucha B, Ozaltin F, Hinkes B, Hasselbacher K, Ruf RG, Schultheiss M, Hangan D, Hoskins BE, Everding AS, Bogdanovic R, Seeman T, Hoppe B, Hildebrandt F (2006) Mutations in the Wilms’ tumor 1 gene cause isolated steroid resistant nephrotic syndrome and occur in exons 8 and 9. Pediatr Res 59:325–331CrossRefPubMed

31.

Zietse R, Wenting GJ, Kramer P, Schalekamp MA, Weimar W (1992) Effects of cyclosporin A on glomerular barrier function in the nephrotic syndrome. Clin Sci 82:641–650CrossRef

32.

Remuzzi A, Fassi A, Bertani T, Perico N, Remuzzi G (1999) ACE inhibition induces regression of proteinuria and halts progression of renal damage in a genetic model of progressive nephropathy. Am J Kidney Dis 34:626–632CrossRefPubMed

33.

Wagner KD, Wagner N, Guo JK, Elger M, Dallman MJ, Bugeon L, Schedl A (2006) An Inducible mouse model for PAX2-dependent glomerular disease: Insights into a complex pathogenesis. Curr Biol 16: 793–800CrossRefPubMed

Titel: Renin-angiotensin axis blockade reduces proteinuria in presymptomatic patients with familial FSGS
verfasst von: Lawrence Copelovitch
Marta Guttenberg
Martin R. Pollak
Bernard S. Kaplan
Publikationsdatum: 01.10.2007
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology / Ausgabe 10/2007
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-007-0505-3

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