Additive antiproteinuric effect of enalapril and losartan in children with hemolytic uremic syndrome

Pediatr Nephrol. 2013 May;28(5):745-50. doi: 10.1007/s00467-012-2374-7. Epub 2012 Dec 20.

Abstract

Background: Angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers decrease postdiarrheal hemolytic uremic syndrome (D + HUS) sequelar proteinuria. However, proteinuria may persist in some patients. In nephropathies other than D + HUS, an additive antiproteinuric effect with coadministration of both drugs has been observed.

Methods: To assess such an effect in D + HUS, 17 proteinuric children were retrospectively studied. After a median period of 1 year post-acute stage (range 0.5-1.9) patients received enalapril alone for a median of 2.6 years (range 0.33-12.0) at a median dose of 0.4 mg/kg/day (range 0.2-0.56). As proteinuria persisted, losartan was added at a median dose of 1.0 mg/kg/day (range 0.5-1.5) during 2.1 years (range 0.5-5.0).

Results: The decrease in proteinuria with enalapril was 58.0 %, which was further reduced to 83.8 % from the initial value after losartan introduction. The percentage of reduction was significantly greater with the association of both drugs (p = 0.0006) compared with the effect of enalapril exclusively (p = 0.023). Serum potassium, glomerular filtration rate, and blood pressure remained unchanged.

Conclusions: Our results suggest that adding losartan to persisting proteinuric D + HUS children already on enalapril is safe and reduces proteinuria more effectively. Whereas this effect is associated with long-term kidney protection, it should be determined by prospective controlled studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Child
  • Child, Preschool
  • Diarrhea / complications
  • Diarrhea / diagnosis
  • Diarrhea / drug therapy*
  • Drug Therapy, Combination
  • Enalapril / adverse effects
  • Enalapril / therapeutic use*
  • Female
  • Hemolytic-Uremic Syndrome / complications
  • Hemolytic-Uremic Syndrome / diagnosis
  • Hemolytic-Uremic Syndrome / drug therapy*
  • Humans
  • Infant
  • Losartan / adverse effects
  • Losartan / therapeutic use*
  • Male
  • Proteinuria / diagnosis
  • Proteinuria / drug therapy*
  • Proteinuria / etiology
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Enalapril
  • Losartan

Supplementary concepts

  • Diarrhea prodrome + Hemolytic-Uremic Syndrome