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Published in: Pediatric Nephrology 5/2013

01-05-2013 | Original Article

Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome

Authors: Nicholas J. A. Webb, Shahnaz Shahinfar, Thomas G. Wells, Rachid Massaad, Gilbert W. Gleim, Christine McCrary Sisk, Chun Lam

Published in: Pediatric Nephrology | Issue 5/2013

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Abstract

Background

A previous subgroup analysis of a 12-week, double-blind study demonstrated that losartan significantly lowered proteinuria versus placebo and amlodipine and was well tolerated in children (1–17 years old) with proteinuria secondary to Alport syndrome. The present subgroup analysis of the open-label, extension phase of this study assessed the long-term efficacy and tolerability of losartan versus enalapril.

Methods

Patients who had completed the double-blind study were re-randomized to losartan or enalapril and followed for proteinuria and renal function for up to 3 years.

Results

Twenty-seven patients with Alport syndrome were randomized to losartan (0.44-2.23 mg/kg/day; n = 15) or enalapril (0.07-0.72 mg/kg/day; n = 12). The least-squares (LS) mean percent change from week 12 in urinary protein to creatinine ratio (UPr/Cr was +1.1 % in the losartan group versus a further 13.9 % reduction in the enalapril group (GMR [95 % CI] = 1.2 [0.7, 2.0]); the LS mean change from week 12 in estimated glomerular filtration rate (eGFR) was −6.4 ml/min/1.73 m2 in the losartan group versus −9.1 ml/min/1.73 m2 in the enalapril group. The adverse event incidence was low and comparable in both treatment groups.

Conclusions

In children with proteinuria secondary to Alport syndrome, losartan maintained proteinuria reduction, and enalapril produced a further proteinuria reduction over the 3-year study period. Both agents were generally well tolerated.
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Literature
1.
go back to reference Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Kashtan CE, Gubler MC (2009) Inherited glomerular diseases. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N (eds) Pediatric nephrology. Springer, Berlin Heidelberg New York, pp 622–628CrossRef Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Kashtan CE, Gubler MC (2009) Inherited glomerular diseases. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N (eds) Pediatric nephrology. Springer, Berlin Heidelberg New York, pp 622–628CrossRef
2.
go back to reference Gross O, Kashtan CE (2009) Treatment of Alport syndrome: beyond animal models. Kidney Int 76:599–603PubMedCrossRef Gross O, Kashtan CE (2009) Treatment of Alport syndrome: beyond animal models. Kidney Int 76:599–603PubMedCrossRef
3.
go back to reference Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869PubMedCrossRef Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869PubMedCrossRef
4.
go back to reference Fernandez-Andrade C, Russo D, Iversen B, Zucchelli P, Aranda P, Guerra L, Casado S (1998) Comparison of losartan and amlodipine in renally impaired hypertensive patients. Kidney Int Suppl 68:S120–S124PubMed Fernandez-Andrade C, Russo D, Iversen B, Zucchelli P, Aranda P, Guerra L, Casado S (1998) Comparison of losartan and amlodipine in renally impaired hypertensive patients. Kidney Int Suppl 68:S120–S124PubMed
5.
go back to reference Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329:1456–1462PubMedCrossRef Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329:1456–1462PubMedCrossRef
6.
go back to reference Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I (2001) Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345:851–860PubMedCrossRef Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I (2001) Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345:851–860PubMedCrossRef
7.
go back to reference Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, Ponticelli C, Ritz E, Zucchelli P (1996) Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 334:939–945PubMedCrossRef Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, Ponticelli C, Ritz E, Zucchelli P (1996) Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 334:939–945PubMedCrossRef
8.
go back to reference GISEN The 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. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet 349:1857–1863CrossRef GISEN The 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. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet 349:1857–1863CrossRef
9.
go back to reference Kashtan CE, Ding J, Gregory M, Gross O, Heidet L, Knebelmann B, Rheault M, Licht C (2012) Clinical practice recommendations for the treatment of Alport syndrome: a statement of the Alport Syndrome Research Collaborative. Pediatr Nephrol. doi:10.1007/s00467-012-2138-4 Kashtan CE, Ding J, Gregory M, Gross O, Heidet L, Knebelmann B, Rheault M, Licht C (2012) Clinical practice recommendations for the treatment of Alport syndrome: a statement of the Alport Syndrome Research Collaborative. Pediatr Nephrol. doi:10.​1007/​s00467-012-2138-4
10.
go back to reference Webb NJ, Lam C, Shahinfar S, Strehlau J, Wells TG, Gleim GW, Le Bailly DT (2011) Efficacy and safety of losartan in children with Alport syndrome–results from a subgroup analysis of a prospective, randomized, placebo- or amlodipine-controlled trial. Nephrol Dial Transplant 26:2521–2526PubMedCrossRef Webb NJ, Lam C, Shahinfar S, Strehlau J, Wells TG, Gleim GW, Le Bailly DT (2011) Efficacy and safety of losartan in children with Alport syndrome–results from a subgroup analysis of a prospective, randomized, placebo- or amlodipine-controlled trial. Nephrol Dial Transplant 26:2521–2526PubMedCrossRef
11.
go back to reference Webb NJ, Lam C, Loeys T, Shahinfar S, Strehlau J, Wells TG, Santoro E, Manas D, Gleim GW (2010) Randomized, double-blind, controlled study of losartan in children with proteinuria. Clin J Am Soc Nephrol 5:417–424PubMedCrossRef Webb NJ, Lam C, Loeys T, Shahinfar S, Strehlau J, Wells TG, Santoro E, Manas D, Gleim GW (2010) Randomized, double-blind, controlled study of losartan in children with proteinuria. Clin J Am Soc Nephrol 5:417–424PubMedCrossRef
12.
go back to reference Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263PubMed Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263PubMed
13.
go back to reference Webb NJA, Shahinfar S, Wells TG, Massaad R, Gleim GW, Santoro EP, Sisk CM, Lam C (2012) Losartan and enalapril are comparable in reducing proteinuria in children. Kidney Int. doi:10.1038/ki.2012.210 Webb NJA, Shahinfar S, Wells TG, Massaad R, Gleim GW, Santoro EP, Sisk CM, Lam C (2012) Losartan and enalapril are comparable in reducing proteinuria in children. Kidney Int. doi:10.​1038/​ki.​2012.​210
14.
go back to reference National High Blood Pressure Education Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576CrossRef National High Blood Pressure Education Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576CrossRef
15.
go back to reference Wuhl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Moller K, Wigger M, Peruzzi L, Mehls O, Schaefer F (2009) Strict blood-pressure control and progression of renal failure in children. N Engl J Med 361:1639–1650PubMedCrossRef Wuhl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Moller K, Wigger M, Peruzzi L, Mehls O, Schaefer F (2009) Strict blood-pressure control and progression of renal failure in children. N Engl J Med 361:1639–1650PubMedCrossRef
16.
go back to reference Gross O, Licht C, Anders HJ, Hoppe B, Beck B, Tonshoff B, Hocker B, Wygoda S, Ehrich JH, Pape L, Konrad M, Rascher W, Dotsch J, Muller-Wiefel DE, Hoyer P, Knebelmann B, Pirson Y, Grunfeld JP, Niaudet P, Cochat P, Heidet L, Lebbah S, Torra R, Friede T, Lange K, Muller GA, Weber M (2012) Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int 81:494–501PubMedCrossRef Gross O, Licht C, Anders HJ, Hoppe B, Beck B, Tonshoff B, Hocker B, Wygoda S, Ehrich JH, Pape L, Konrad M, Rascher W, Dotsch J, Muller-Wiefel DE, Hoyer P, Knebelmann B, Pirson Y, Grunfeld JP, Niaudet P, Cochat P, Heidet L, Lebbah S, Torra R, Friede T, Lange K, Muller GA, Weber M (2012) Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int 81:494–501PubMedCrossRef
Metadata
Title
Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome
Authors
Nicholas J. A. Webb
Shahnaz Shahinfar
Thomas G. Wells
Rachid Massaad
Gilbert W. Gleim
Christine McCrary Sisk
Chun Lam
Publication date
01-05-2013
Publisher
Springer-Verlag
Published in
Pediatric Nephrology / Issue 5/2013
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-012-2372-9

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