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Pediatric Nephrology

, Volume 18, Issue 10, pp 1038–1043 | Cite as

Antiproteinuric effects of enalapril and losartan: a pilot study

  • Colin Thomas WhiteEmail author
  • Catherine Fiona Macpherson
  • Robert Morrison Hurley
  • Douglas George Matsell
Original Article

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.

Keywords

Proteinuria Angiotensin converting enzyme inhibitors Angiotensin receptor antagonists Randomized control trial Double-blind crossover study 

Notes

Acknowledgements

The data in this paper were presented in part at the Canadian Society of Nephrology Annual Meeting in Ottawa, March 2002. The authors would like to thank the Child Health Research Institute, at the University of Western Ontario, for their generous financial support of this study, and Daniel Noël PhD of the University of Western Ontario and Ruth Milner clinical research support group of the University of British Columbia for their assistance with the statistical analysis.

References

  1. 1.
    Taal MW, Brenner BM (2000) Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int 57:1803–1817CrossRefPubMedGoogle Scholar
  2. 2.
    Trachtman H, Gauthier B (1988) Effect of angiotensin-converting enzyme inhibitor therapy on proteinuria in children with renal disease. J Pediatr 112:295–298PubMedGoogle Scholar
  3. 3.
    Milliner DS, Morgenstern BZ (1991) Angiotensin converting enzyme inhibitors for reduction of proteinuria in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 5:587–590PubMedGoogle Scholar
  4. 4.
    Lama G, Salsano ME, Pedulla M, Grassia C, Ruocco G (1997) Angiotensin converting enzyme inhibitors and reflux nephropathy: 2 year follow-up. Pediatr Nephrol 11:714–718CrossRefPubMedGoogle Scholar
  5. 5.
    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 15:113–118CrossRefPubMedGoogle Scholar
  6. 6.
    Proesmans W, Van Wambeke I, Van Dyck M (1996) Long-term therapy with enalapril in patients with nephrotic-range proteinuria. Pediatr Nephrol 10:587–589CrossRefPubMedGoogle Scholar
  7. 7.
    Proesmans W, Knockaert H, Trouet D (2000) Enalapril in paediatric patients with Alport syndrome: 2 years' experience. Eur J Pediatr 159:430–433CrossRefPubMedGoogle Scholar
  8. 8.
    Schror K (1992) Role of prostaglandins in the cardiovascular effects of bradykinin and angiotensin-converting enzyme inhibitors. J Cardiovasc Pharmacol 20 [Suppl] 9:S68–S73Google Scholar
  9. 9.
    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 90:1932–1943PubMedGoogle Scholar
  10. 10.
    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 152:127–133CrossRefPubMedGoogle Scholar
  11. 11.
    Remuzzi G, Ruggenenti P, Benigni A (1997) Understanding the nature of renal disease progression. Kidney Int 51:2–15PubMedGoogle Scholar
  12. 12.
    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 57:1962–1967CrossRefPubMedGoogle Scholar
  13. 13.
    Aiello S, Remuzzi G, Noris M (1998) Nitric oxide/endothelin balance after nephron reduction. Kidney Int [Suppl] 65:S63–S67Google Scholar
  14. 14.
    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 57:147–158CrossRefPubMedGoogle Scholar
  15. 15.
    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–S73Google Scholar
  16. 16.
    Kriz W, Gretz N, Lemley KV (1988) Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 54:687–697Google Scholar
  17. 17.
    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 10:69–76PubMedGoogle Scholar
  18. 18.
    Nangaku M, Pippin J, Couser WG (1999) Complement membrane attack complex (C5b-9) mediates interstitial disease in experimental nephrotic syndrome. J Am Soc Nephrol 10:2323–2331PubMedGoogle Scholar
  19. 19.
    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 58:1219–1227CrossRefPubMedGoogle Scholar
  20. 20.
    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 307:652–659PubMedGoogle Scholar
  21. 21.
    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 76:612–619PubMedGoogle Scholar
  22. 22.
    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 71:68–76CrossRefPubMedGoogle Scholar
  23. 23.
    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 21:53–57CrossRefPubMedGoogle Scholar
  24. 24.
    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 34:2072–2077CrossRefPubMedGoogle Scholar
  25. 25.
    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 33:850–855PubMedGoogle Scholar
  26. 26.
    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 62:1020–1025CrossRefPubMedGoogle Scholar
  27. 27.
    Anon (1990) Laboratory reference values. In: Oski FA, DeAngelis C, Feigin RD, Warshaw JB (eds) Principles and practice of pediatrics. Lippincott, Philadelphia, p1979Google Scholar
  28. 28.
    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 98:649–658PubMedGoogle Scholar

Copyright information

© IPNA 2003

Authors and Affiliations

  • Colin Thomas White
    • 1
    Email author
  • Catherine Fiona Macpherson
    • 2
  • Robert Morrison Hurley
    • 1
  • Douglas George Matsell
    • 3
  1. 1.Division of NephrologyBritish Columbia's Children's HospitalVancouverCanada
  2. 2.Children's Hospital and Regional Health CenterSeattleUSA
  3. 3.Section of Pediatric NephrologyChildren's Hospital of Western OntarioLondonCanada

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