Time course of the antiproteinuric and renal haemodynamic responses to losartan in microalbuminuric IDDM.
BACKGROUND
Interference in the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors has proven to be effective in lowering albuminuria in patients with insulin-dependent diabetes mellitus (IDDM). We studied whether angiotensin II receptor antagonism reduces urinary albumin excretion (UAE) in IDDM patients, and the relationship between the antiproteinuric effect and changes in systemic and renal haemodynamics.


METHODS
Nine IDDM patients with microalbuminuria (30-300 mg/24 h) were studied. 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 losartan treatment. Effective renal plasma flow (ERPF) was significantly increased on the third day of treatment and remained stable throughout the treatment period. Glomerular filtration rate (GFR) did not change throughout the study. Filtration fraction (FF) was maximally lowered on the third day of treatment and remained stable during treatment. UAE was already significantly lowered after 2 days of treatment, during both the day and night, and remained stable throughout the treatment period. The time course of the changes in UAE paralleled that of the changes in MAP, ERPF and FF.


CONCLUSIONS
The angiotensin receptor antagonist losartan effectively lowers UAE in microalbuminuric IDDM patients. The changes observed in renal haemodynamics 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.
Department of Nephrology, University Hospital Groningen, Groningen, The Netherlands.
H
H
Buter
G
G
Navis
R P
RP
Dullaart
D
D
de Zeeuw
P E
PE
de Jong
D000419:Albuminuria / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology / Q000652:urine; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D019808:Losartan / Q000008:administration & dosage* / Q000627:therapeutic use; D012079:Renal Circulation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D019808:Losartan