Time course of the antiproteinuric and antihypertensive effect of losartan in diabetic nephropathy.
BACKGROUND
Blockade of the renin-angiotensin system is the primary target in the treatment of diabetic kidney disease. Angiotensin II subtype 1 (AT1) receptor antagonists reduce albuminuria and lower blood pressure, but the initial time course of these effects after initiation of treatment is unknown. We evaluated the time course of the antihypertensive and antialbuminuric effect after initiation of AT1 receptor blockade by losartan in diabetic nephropathy.


METHODS
Ten hypertensive type 1 diabetic patients with diabetic nephropathy were included in the study. After a washout period of 4 weeks, patients received losartan 100 mg once daily for 28 days. Every morning, one urine sample was collected for daily determination of albumin/creatinine ratio. Twenty-four hour blood pressure (Takeda TM2420), plasma renin and plasma creatinine were measured at baseline and days 7, 14 and 28.


RESULTS
Baseline levels of urinary albumin/creatinine ratio and 24 h mean arterial blood pressure were 676 (402-1136) mg/g (geometric mean and 95% CI, respectively) and 100+/-3 mmHg (mean +/- SEM). Albumin/creatinine ratio was significantly reduced after 7 days of treatment by 29% (15-41) (95% CI) without significant further reductions during the 28 day study period (P<0.01 vs baseline). Mean arterial blood pressure was significantly lowered by 7 mmHg after 7 days of treatment and remained unchanged throughout the study (P<0.01 vs baseline). Plasma renin was significantly increased from baseline after initiation of losartan treatment and stabilized after 7 days (P<0.01). We found no changes in plasma creatinine during the study.


CONCLUSIONS
The initial time course of the reduction in arterial blood pressure and albuminuria are concordant, which suggests that systemic and renal haemodynamic mechanisms are of primary importance in the reduction of albuminuria.
Andersen
Steen
S
Steno Diabetes Center, Niels Steensensvej 2, DK-2820 Gentofte, Denmark. STAN@dadlnet.dk
Jacobsen
Peter
P
Tarnow
Lise
L
Rossing
Peter
P
Juhl
Tina R
TR
Parving
Hans-Henrik
HH
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D012083:Renin / Q000097:blood; D013997:Time Factors
D000959:Antihypertensive Agents; D003404:Creatinine; D012083:Renin; D019808:Losartan