Time course of the antiproteinuric and renal haemodynamic responses to losartan in microalbuminuric IDDM

Background. Interference in the renin-angiotensin system with angiotensin-c onverting enzyme (ACE) inhibitors has proven to be effective in lowering al buminuria in patients with insulin-dependent diabetes mellitus (IDDM). We s tudied whether angiotensin II receptor antagonism reduces urinary albumin e xcretion (UAE) in IDDM patients, and the relationship between the antiprote inuric effect and changes in systemic and renal haemodynamics. Methods. Nine IDDM patients with microalbuminuria (30-300 mg/24 h) were stu died. patients were studied after a 4 week placebo period, on days 3, 7 and 28 of treatment with losartan 50 mg once daily, and after a 4 week placebo -controlled recovery period. Results. Mean arterial pressure (MAP) was only slightly lowered during losa rtan treatment. Effective renal plasma flow (ERPF) was significantly increa sed on the third day of treatment and remained stable throughout the treatm ent period. Glomerular filtration rate (GFR) did not change throughout the study. Filtration fraction (FF) was maximally lowered on the third day of t reatment and remained stable during treatment. UAE was already significantl y lowered after 2 days of treatment, during both the day and night, and rem ained stable throughout the treatment period. The time course of the change s in UAE paralleled that of the changes in MAP, ERPF and FF. Conclusions. The angiotensin receptor antagonist losartan effectively lower s UAE in microalbuminuric IDDM patients. The changes observed in renal haem odynamics and UAE are concordant in time and maximal within only a few days of treatment. These results support the importance of the specific effects of interference in the renin angiotensin system (RAS) in microalbuminuric IDDM on blood pressure and renal haemodynamics in reducing urinary protein leakage, rather than non-haemodynamic, structural changes of the glomerular basement membrane.