Angiotensin receptor antagonists are effective in reducing
proteinuria by an action independent of blood pressure. As a consequence, such agents retard progressive renal dysfunction in adults with chronic
proteinuria. Long-term efficacy and tolerability data in children are unavailable.
METHODS: Efficacy of
losartan in reducing
proteinuria and in preserving renal function was prospectively assessed in 52 consecutive children under 18 years of age with chronic proteinuric renal disorders, an initial
creatinine clearance > or =25 mL/min/1.73 m(2), and a minimum of two or more follow-up visits. Thirty had
proteinuria (P), and 22 had
proteinuria combined with
hypertension (P+H). Adverse effects were also evaluated.
RESULTS:
Proteinuria had persisted or increased during a mean interval of 8.5 months before initiation of
losartan at a mean dosage of 0.8 mg/kg/d. Mean
protein excretion before starting
losartan was 2453 mg/m(2)/d and fell by 34% at a mean follow-up time of six weeks (visit I, P<.05), and between 64% and 67% at mean follow-up periods of 0.38, 0.71, and 2.48 years corresponding to visits II, III, and IV (all P<.001 compared with baseline). The proportion of children with
protein excretion exceeding 40 mg/m(2)/h (nephrotic range
proteinuria) or
nephrotic syndrome (>3500 mg/1.73 m(2)/d) fell from 42% and 40% at the start, to 24% and 8%, respectively, at visit IV (P<.01). Mean
creatinine clearance as well as serum
potassium and total CO(2) levels remained unchanged during the time of follow-up. Reduction in
proteinuria in the P subgroup alone correlated with lowering in diastolic blood pressure at visit II and with both diastolic and systolic blood pressure at visits III and IV (all P<.05); it was largely independent of reduction in blood pressure in the P+H subgroup. The concomitant use of
immunosuppressive agents in 28 of the 52 children had an influence on
proteinuria only at baseline and at visit I (P<.05). There was no significant change in height or body mass index Z scores. Thirteen children had adverse effects potentially ascribed to
losartan; most of these either improved or resolved with dosage adjustment or resulted in its discontinuation in 9 of the 52 children (17%).
CONCLUSION:
Losartan therapy was associated with a marked and sustained reduction in
proteinuria and in preservation of GFR in children with chronic proteinuric disorders. The association between
proteinuria and systemic blood pressure reduction was complex: it was largely limited to the first year of
losartan therapy and was more pronounced in the normotensive subgroup.
Losartan was generally well tolerated.