Long-term antiproteinuric and renoprotective efficacy and safety of losartan in children with proteinuria.
BACKGROUND
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%).


CONCLUSIONS
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.
Ellis
Demetrius
D
Division of Pediatric Nephrology, Children's Hospital of Pittsburgh and Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. ellisd@chplink.chp.edu
Vats
Abhay
A
Moritz
Michael L
ML
Reitz
Susanne
S
Grosso
Mary Jo
MJ
Janosky
Janine E
JE
D000293:Adolescent; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007674:Kidney Diseases / Q000517:prevention & control*; D019808:Losartan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D011188:Potassium / Q000097:blood; D011446:Prospective Studies; D011507:Proteinuria / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D012720:Severity of Illness Index; D013995:Time
D000959:Antihypertensive Agents; D003404:Creatinine; D019808:Losartan; D011188:Potassium