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Published in: Pediatric Nephrology 10/2003

01-10-2003 | Original Article

Antiproteinuric effects of enalapril and losartan: a pilot study

Authors: Colin Thomas White, Catherine Fiona Macpherson, Robert Morrison Hurley, Douglas George Matsell

Published in: Pediatric Nephrology | Issue 10/2003

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Abstract

In this randomized double-blind crossover trial we compared the antiproteinuric effects of enalapril and losartan in six children with proteinuria and underlying renal injury. The primary endpoint was reduction in proteinuria during therapy. The study had two 8-week on-drug arms, with a 4-week washout period between. Baseline proteinuria was similar, enalapril 87 mg/m2 per hour and losartan 77 mg/m2 per hour. The mean reduction in proteinuria with enalapril was 48% (37%–57%) with a standard error of the mean of 3%; with losartan it was 31% (14%–52%) with a standard error of the mean of 7%. Although there was a significant reduction in proteinuria with the use of both drugs, the difference in reduction of proteinuria, 48% versus 31%, was not considered clinically significant. Potassium remained below 4.5 mmol/l in all patients. No patient's creatinine rose more than the standard deviation of our assay. Blood pressure (BP) control was acceptable in four of the six patients; two patients had persistently elevated or increased BP on each drug. Side effects were minimal; none requiring withdrawal, one requiring dose reduction. Studies have shown that angiotensin converting enzyme inhibitors can reduce proteinuria in children with renal disorders. No studies to date have examined the reduction of proteinuria achieved by angiotensin receptor blockers. Our study, although small, suggests that angiotensin receptor blockers may reduce proteinuria as effectively, and as safely, as angiotensin converting enzyme inhibitors.
Literature
1.
go back to reference Taal MW, Brenner BM (2000) Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int 57:1803–1817CrossRefPubMed Taal MW, Brenner BM (2000) Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int 57:1803–1817CrossRefPubMed
2.
go back to reference Trachtman H, Gauthier B (1988) Effect of angiotensin-converting enzyme inhibitor therapy on proteinuria in children with renal disease. J Pediatr 112:295–298PubMed Trachtman H, Gauthier B (1988) Effect of angiotensin-converting enzyme inhibitor therapy on proteinuria in children with renal disease. J Pediatr 112:295–298PubMed
3.
go back to reference Milliner DS, Morgenstern BZ (1991) Angiotensin converting enzyme inhibitors for reduction of proteinuria in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 5:587–590PubMed Milliner DS, Morgenstern BZ (1991) Angiotensin converting enzyme inhibitors for reduction of proteinuria in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 5:587–590PubMed
4.
go back to reference Lama G, Salsano ME, Pedulla M, Grassia C, Ruocco G (1997) Angiotensin converting enzyme inhibitors and reflux nephropathy: 2 year follow-up. Pediatr Nephrol 11:714–718CrossRefPubMed Lama G, Salsano ME, Pedulla M, Grassia C, Ruocco G (1997) Angiotensin converting enzyme inhibitors and reflux nephropathy: 2 year follow-up. Pediatr Nephrol 11:714–718CrossRefPubMed
5.
go back to reference Soergal M, Verho M, Wühl E, Gellermann J, Teichert L, Schärer K (2000) Effect of ramipril on ambulatory blood pressure and albuminuria in renal hypertension. Pediatr Nephrol 15:113–118CrossRefPubMed Soergal M, Verho M, Wühl E, Gellermann J, Teichert L, Schärer K (2000) Effect of ramipril on ambulatory blood pressure and albuminuria in renal hypertension. Pediatr Nephrol 15:113–118CrossRefPubMed
6.
go back to reference Proesmans W, Van Wambeke I, Van Dyck M (1996) Long-term therapy with enalapril in patients with nephrotic-range proteinuria. Pediatr Nephrol 10:587–589CrossRefPubMed Proesmans W, Van Wambeke I, Van Dyck M (1996) Long-term therapy with enalapril in patients with nephrotic-range proteinuria. Pediatr Nephrol 10:587–589CrossRefPubMed
7.
go back to reference Proesmans W, Knockaert H, Trouet D (2000) Enalapril in paediatric patients with Alport syndrome: 2 years' experience. Eur J Pediatr 159:430–433CrossRefPubMed Proesmans W, Knockaert H, Trouet D (2000) Enalapril in paediatric patients with Alport syndrome: 2 years' experience. Eur J Pediatr 159:430–433CrossRefPubMed
8.
go back to reference Schror K (1992) Role of prostaglandins in the cardiovascular effects of bradykinin and angiotensin-converting enzyme inhibitors. J Cardiovasc Pharmacol 20 [Suppl] 9:S68–S73 Schror K (1992) Role of prostaglandins in the cardiovascular effects of bradykinin and angiotensin-converting enzyme inhibitors. J Cardiovasc Pharmacol 20 [Suppl] 9:S68–S73
9.
go back to reference Riser BL, Cortes P, Zhao X, Berstein J, Dumler F, Nairns RG (1992) Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat. J Clin Invest 90:1932–1943PubMed Riser BL, Cortes P, Zhao X, Berstein J, Dumler F, Nairns RG (1992) Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat. J Clin Invest 90:1932–1943PubMed
10.
go back to reference Romero F, Rodriguez-Iturbe B, Pons H, Parra G, Quiroz Y, Rincon J, Gonzalez L (2000) Mycophenolate mofetil treatment reduces cholesterol-induced atherosclerosis in the rabbit. Atherosclerosis 152:127–133CrossRefPubMed Romero F, Rodriguez-Iturbe B, Pons H, Parra G, Quiroz Y, Rincon J, Gonzalez L (2000) Mycophenolate mofetil treatment reduces cholesterol-induced atherosclerosis in the rabbit. Atherosclerosis 152:127–133CrossRefPubMed
11.
go back to reference Remuzzi G, Ruggenenti P, Benigni A (1997) Understanding the nature of renal disease progression. Kidney Int 51:2–15PubMed Remuzzi G, Ruggenenti P, Benigni A (1997) Understanding the nature of renal disease progression. Kidney Int 51:2–15PubMed
12.
go back to reference Hebert LA, Agarwal G, Sedmak DD, Mahan JD, Becker W, Nagaraja HN (2000) Proximal tubular epithelial hyperplasia in patients with chronic glomerular proteinuria. Kidney Int 57:1962–1967CrossRefPubMed Hebert LA, Agarwal G, Sedmak DD, Mahan JD, Becker W, Nagaraja HN (2000) Proximal tubular epithelial hyperplasia in patients with chronic glomerular proteinuria. Kidney Int 57:1962–1967CrossRefPubMed
13.
go back to reference Aiello S, Remuzzi G, Noris M (1998) Nitric oxide/endothelin balance after nephron reduction. Kidney Int [Suppl] 65:S63–S67 Aiello S, Remuzzi G, Noris M (1998) Nitric oxide/endothelin balance after nephron reduction. Kidney Int [Suppl] 65:S63–S67
14.
go back to reference Mezzano SA, Droguett MA, Burgos ME, Ardiles LG, Aros CA, Caorsi I, Egido J (2000) Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human membranous nephropathy. Kidney Int 57:147–158CrossRefPubMed Mezzano SA, Droguett MA, Burgos ME, Ardiles LG, Aros CA, Caorsi I, Egido J (2000) Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human membranous nephropathy. Kidney Int 57:147–158CrossRefPubMed
15.
go back to reference Terzi F, Burtin M, Friedlander G (1998) Early molecular mechanisms in the progression of renal failure: role of growth factors and protooncogenes. Kidney Int [Suppl] 65:S68–S73 Terzi F, Burtin M, Friedlander G (1998) Early molecular mechanisms in the progression of renal failure: role of growth factors and protooncogenes. Kidney Int [Suppl] 65:S68–S73
16.
go back to reference Kriz W, Gretz N, Lemley KV (1988) Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 54:687–697 Kriz W, Gretz N, Lemley KV (1988) Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 54:687–697
17.
go back to reference Tang S, Sheerin NS, Zhou W, Brown Z, Sacks SH (1999) Apical proteins stimulate complement synthesis by cultured human proximal tubular epithelial cells. J Am Soc Nephrol 10:69–76PubMed Tang S, Sheerin NS, Zhou W, Brown Z, Sacks SH (1999) Apical proteins stimulate complement synthesis by cultured human proximal tubular epithelial cells. J Am Soc Nephrol 10:69–76PubMed
18.
go back to reference Nangaku M, Pippin J, Couser WG (1999) Complement membrane attack complex (C5b-9) mediates interstitial disease in experimental nephrotic syndrome. J Am Soc Nephrol 10:2323–2331PubMed Nangaku M, Pippin J, Couser WG (1999) Complement membrane attack complex (C5b-9) mediates interstitial disease in experimental nephrotic syndrome. J Am Soc Nephrol 10:2323–2331PubMed
19.
go back to reference Brown NJ, Nakamura S, Ma L, Nakamura I, Donnert E, Freeman M, Vaughan DE, Fogo AB (2000) Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo. Kidney Int 58:1219–1227CrossRefPubMed Brown NJ, Nakamura S, Ma L, Nakamura I, Donnert E, Freeman M, Vaughan DE, Fogo AB (2000) Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo. Kidney Int 58:1219–1227CrossRefPubMed
20.
go back to reference Brenner BM, Meyer TW, Hostetter TH (1982) Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med 307:652–659PubMed Brenner BM, Meyer TW, Hostetter TH (1982) Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med 307:652–659PubMed
21.
go back to reference Anderson S, Meyer TW, Rennke HG, Brenner BM (1985) Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest 76:612–619PubMed Anderson S, Meyer TW, Rennke HG, Brenner BM (1985) Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest 76:612–619PubMed
22.
go back to reference Maillard MP, Wurzner G, Nussberger J, Centeno C, Burnier M, Brunner HR (2002) Comparative angiotensin II receptor blockade in healthy volunteers: the importance of dosing. Clin Pharmacol Ther 71:68–76CrossRefPubMed Maillard MP, Wurzner G, Nussberger J, Centeno C, Burnier M, Brunner HR (2002) Comparative angiotensin II receptor blockade in healthy volunteers: the importance of dosing. Clin Pharmacol Ther 71:68–76CrossRefPubMed
23.
go back to reference Roig E, Perez-Villa F, Morales M, Jimenez W, Orus J, Heras M, Sanz G (2000) Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur Heart J 21:53–57CrossRefPubMed Roig E, Perez-Villa F, Morales M, Jimenez W, Orus J, Heras M, Sanz G (2000) Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur Heart J 21:53–57CrossRefPubMed
24.
go back to reference Struthers AD, MacFadyen R, Fraser Callum, Robson J, Morton JJ, Junot C, Ezan E (1999) Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failure. J Am Coll Cardiol 34:2072–2077CrossRefPubMed Struthers AD, MacFadyen R, Fraser Callum, Robson J, Morton JJ, Junot C, Ezan E (1999) Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failure. J Am Coll Cardiol 34:2072–2077CrossRefPubMed
25.
go back to reference Mazzolai L, Maillard M, Rossat J, Nussberger J, Brunner HR, Burnier M (1999) Angiotensin II receptor blockade in normotensive subjects: a direct comparison of three AT1 receptor antagonists. Hypertension 33:850–855PubMed Mazzolai L, Maillard M, Rossat J, Nussberger J, Brunner HR, Burnier M (1999) Angiotensin II receptor blockade in normotensive subjects: a direct comparison of three AT1 receptor antagonists. Hypertension 33:850–855PubMed
26.
go back to reference Laverman GD, Navis G, Henning RH, De Jong PE, De Zeeuw D (2002) Dual renin-angiotensin system blockade at optimal doses for proteinuria. Kidney Int 62:1020–1025CrossRefPubMed Laverman GD, Navis G, Henning RH, De Jong PE, De Zeeuw D (2002) Dual renin-angiotensin system blockade at optimal doses for proteinuria. Kidney Int 62:1020–1025CrossRefPubMed
27.
go back to reference Anon (1990) Laboratory reference values. In: Oski FA, DeAngelis C, Feigin RD, Warshaw JB (eds) Principles and practice of pediatrics. Lippincott, Philadelphia, p1979 Anon (1990) Laboratory reference values. In: Oski FA, DeAngelis C, Feigin RD, Warshaw JB (eds) Principles and practice of pediatrics. Lippincott, Philadelphia, p1979
28.
go back to reference Anon (1996) Update on the 1997 Task Force Report on High Blood Pressure in Children and Adolescents: a Working Group Report from the National High Blood Pressure Education Program. Pediatrics 98:649–658PubMed Anon (1996) Update on the 1997 Task Force Report on High Blood Pressure in Children and Adolescents: a Working Group Report from the National High Blood Pressure Education Program. Pediatrics 98:649–658PubMed
Metadata
Title
Antiproteinuric effects of enalapril and losartan: a pilot study
Authors
Colin Thomas White
Catherine Fiona Macpherson
Robert Morrison Hurley
Douglas George Matsell
Publication date
01-10-2003
Publisher
Springer-Verlag
Published in
Pediatric Nephrology / Issue 10/2003
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-003-1190-5

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