Antihypertensive and renoprotective efficacy and safety of losartanA long-term study in children with renal disorders

Abstract

Hypertension is a major risk factor for progressive renal failure. We assessed the long term efficacy and safety of losartan in lowering blood pressure (BP) and in preserving renal function in hypertensive children with chronic renal disorders. Losartan was used in 45 consecutive hypertensive children with chronic renal parenchymal disorders and mean glomerular filtration rate (GFR) 99.4 mL/min/1.73 m2. Of the children, 21 had hypertension alone (H) and 24 had both hypertension and proteinuria (H+P). Assessment was done at baseline and at preselected time points: visit I, <0.25 years; visit II, ≥0.25 and <0.5 year;visit III, 0.5 to 1.0 year; and visit IV >1 year. Both BP control and GFR were the principal outcome measures, and proteinuria was a secondary outcome measure. The mean age was 12.85 years and follow-up was 2.42 years (visit IV). Compared with baseline the systolic, diastolic, and mean arterial BP (MABP) fell by 9 to 12 mm Hg (all P < .01) in visit I. Diastolic BP and MABP remained significantly lower in all visits (P < .05 to .001), whereas systolic BP was not statistically lower in visit II. In visit IV the proportion of normotensive children increased significantly compared with baseline (P < .03 for systolic BP, P < .0004 for diastolic BP). In the H+P subgroup, optimal reduction in proteinuria ranging from 66% to 71% occurred in visits II to IV (all P < .01). Mean GFR declined at a rate of 9.3 mL/min/1.73 m2 /year before starting losartan, and 1.4 mL/min/1.73 m2 /year subsequently (P = NS). On long term follow-up, GFR fell by 15.9 mL/min/1.73 m2 in the H subgroup and by 5.5 mL/min/1.73 m2 in the H+P subgroup (P = NS). There was no correlation between BP measures and GFR or between the magnitude of BP lowering and proteinuria. Adverse effects (one serious) led to discontinuation of losartan in five children (11%). Losartan therapy was associated with prolonged and sustained antihypertensive and renoprotective benefits in children with a variety of chronic renal parenchymal disorders. Such benefit may be more pronounced in children with combined hypertension and proteinuria. The agent was well tolerated in the majority of the children.