enalapril and Hemolytic-Uremic-Syndrome

Proteinuria is the main indicator of renal disease progression in many chronic conditions. There is currently little information available on the efficacy, safety, and individual tolerance of patients with post-diarrheal hemolytic uremic syndrome (D+ HUS) nephropathy to therapies involving diet, enalapril, or losartan. A multicenter, double-blind, randomized controlled trail was conducted to evaluate the effect of a normosodic-normoproteic diet (Phase I) and the effect of normosodic-normoproteic diet plus enalapril (0.18-0.27 mg/kg/day) or losartan (0.89-1.34 mg/kg/day) (Phase II) on children with D+ HUS, normal renal function, and persistent, mild (5.1-49.9 mg/kg/day) proteinuria. Dietary intervention reduced the mean protein intake from 3.4 to 2.2 mg/kg/day. Of 137 children, proteinuria normalized in 91 (66.4 %) within 23-45 days; the remaining 46 patients were randomized to diet plus placebo (group 1, n = 16), plus losartan (group 2, n = 16), or enalapril (group 3, n = 14). In groups 1, 2, and 3, proteinuria was reduced by 30.0, 82.0, and 66.3%, respectively, and normalized in six (37.5%), three (81.3%), and 11 (78.6%) patients, respectively (χ(2)= 8.9, p = 0.015). These results suggest that: (1) a normosodic-normoproteic diet can normalize proteinuria in the majority of children with D+ HUS with mild sequelae, (2) the addition of enalapril or losartan to such dietary restrictions of protein further reduces proteinuria, and (3) these therapeutic interventions are safe and well tolerated. Whether these short-term effects can be extended to the long-term remains to be demonstrated.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Child; Child, Preschool; Diarrhea; Diet Therapy; Double-Blind Method; Enalapril; Female; Hemolytic-Uremic Syndrome; Humans; Kidney Failure, Chronic; Losartan; Male; Proteinuria

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.. 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).. 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.. 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.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Child; Child, Preschool; Diarrhea; Drug Therapy, Combination; Enalapril; Female; Hemolytic-Uremic Syndrome; Humans; Infant; Losartan; Male; Proteinuria; Retrospective Studies; Time Factors; Treatment Outcome

Topics: Acute Kidney Injury; Antihypertensive Agents; Biopsy; Child; Diagnosis, Differential; Enalapril; Follow-Up Studies; Hemolytic-Uremic Syndrome; Humans; Hypertension, Renal; Hypertrophy, Left Ventricular; Kidney; Propranolol; Purpura, Thrombotic Thrombocytopenic; Radionuclide Imaging; Renal Dialysis; Severity of Illness Index; Technetium Tc 99m Dimercaptosuccinic Acid; Time Factors; Treatment Outcome

Five patients with severe hemolytic uremic syndrome (HUS) were followed for 10-18 years. Because of proteinuria, arterial hypertension, and reduced glomerular filtration rates, they received either captopril (n=2) or enalapril (n=3), or both (n=1) for 8-15 years. Blood pressure was normalized and proteinuria reduced in all; glomerular filtration improved in three patients and fell moderately in two. Four of the five patients have reached adult age with body weight and height, blood pressure, and serum creatinine levels within the normal range. At the last evaluation, median proteinuria was 220 mg/24 h (range 0-310) and glomerular filtration rate 56 ml/min per 1.73 m(2)(range 40-127). This long-term study indicates a renoprotective effect of angiotensin-converting enzyme inhibitors in patients with sequelae after HUS.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Child, Preschool; Creatinine; Enalapril; Follow-Up Studies; Glomerular Filtration Rate; Hemolytic-Uremic Syndrome; Humans; Hypertension; Kidney; Proteinuria; Time Factors