Optimal dose of losartan for renoprotection in diabetic nephropathy.
BACKGROUND
Angiotensin II subtype-1 receptor antagonists represent a valuable new class of drugs in the treatment of diabetic nephropathy. The aim of our study was to evaluate the optimal dose of losartan for renoprotection and blood pressure reduction in diabetic nephropathy.


METHODS
Fifty consecutive hypertensive type 1 diabetic patients with diabetic nephropathy received increasing doses of losartan, 50, 100, and 150 mg once daily in three periods each lasting 2 months. At baseline and at the end of each treatment period, albuminuria, 24-h blood pressure (TM2420 A&D), and glomerular filtration rate (GFR) ([(51)Cr]EDTA plasma clearance) were determined.


RESULTS
Baseline values of albuminuria (geometric mean (95% CI)) and GFR (means+/-SEM) were 1138 (904-1432) mg/24 h and 91+/-3 ml/min/1.73 m(2), respectively. The blood pressure at baseline was 155/81+/-3/2 mmHg. All doses of losartan reduced albuminuria and blood pressure. Albuminuria was reduced by 30% (95% CI (15-41)) on losartan 50 mg, 48% (35-57) by losartan 100 mg, and 44% (32-56) by losartan 150 mg (all P values <0.01 vs baseline). Losartan 100 mg daily was significantly more effective than 50 mg daily in reducing albuminuria (P<0.01) without differences between the two high doses. Losartan 50, 100, and 150 mg daily decreased systolic/diastolic blood pressures by 7/4, 12/6, and 10/5 mmHg, respectively (all P<0.05). Losartan 100 mg daily was more effective than 50 mg daily in reducing systolic, diastolic, and mean arterial blood pressure (P=0.05), without differences between the high doses. Treatment with losartan 100 and 150 mg lowered GFR by 4 ml/min/1.73 m(2) (P<0.05).


CONCLUSIONS
Our study suggests that the optimal dose of losartan is 100 mg daily for renoprotection and blood pressure reduction in type 1 diabetic patients with diabetic nephropathy.
Andersen
Steen
S
Steno Diabetes Center, Copenhagen, Denmark. STAN@dadlnet.dk
Rossing
Peter
P
Juhl
Tina R
TR
Deinum
Jaap
J
Parving
Hans-Henrik
HH
D000419:Albuminuria; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000150:complications*; D003971:Diastole / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D019808:Losartan / Q000627:therapeutic use*; D013599:Systole / Q000187:drug effects; D013997:Time Factors
D000959:Antihypertensive Agents; D019808:Losartan