The antiproteinuric effect of losartan is systemic blood pressure dependent.
BACKGROUND
It has been suggested that high doses of angiotensin II receptor antagonists (AIIAs) may reduce proteinuria by a non-haemodynamic action additional to their effect on systemic blood pressure.


METHODS
We tested this for the AIIA losartan using a prospective single-blind randomized design in patients with proteinuria (>1 g/24 h) due to non-diabetic chronic renal failure (stable creatinine clearance >20 ml/min) and mild to moderate hypertension (130/80 < blood pressure < 160/110 mmHg). Twenty-one patients were randomized into two groups: group A received losartan 50 mg daily for 4 weeks, then 100 mg daily for 4 weeks; group B received losartan 50 mg daily for 8 weeks. Twenty-four hour ambulatory blood pressure and renal parameters were measured at baseline and at 4 and 8 weeks of treatment.


RESULTS
Overall there was a 7 +/- 2 mmHg fall (mean +/- SEM) in mean daytime systolic blood pressure at 4 weeks, and a 22 +/- 7% fall in protein/creatinine ratio (both P < 0.05), with no difference between groups A and B or between 4 and 8 weeks. These two changes were highly correlated (r = 0.64, P = 0.006, taking both groups together). Changes in diastolic pressure and in night-time systolic pressure did not reach statistical significance. Changes in renal plasma flow (measured by Tc 99m MAGIII), glomerular filtration rate and filtration fraction (measured by 51Cr EDTA) did not reach statistical significance, did not differ between the two groups and did not correlate with effects on proteinuria.


CONCLUSIONS
This study provides no evidence that the effect of losartan on proteinuria has a non-haemodynamic component.
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001795:Blood Pressure Determination; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000175:diagnosis; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control*; D012016:Reference Values; D018570:Risk Assessment; D016037:Single-Blind Method; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D019808:Losartan