Antiproteinuric efficacy of losartan in comparison with amlodipine in non-diabetic proteinuric renal diseases: a double-blind, randomized clinical trial.
BACKGROUND
Proteinuria is a significant independent determinant of the progression of chronic renal diseases. It induces an increased synthesis of angiotensin II, endothelin and profibrogenic growth factors, such as transforming growth factor-beta (TGF-beta), by mesangial and tubular cells. The antiproteinuric effect of angiotensin-converting enzyme inhibitors (ACEIs) in diabetic and non-diabetic nephropathies predicts long-term renoprotection afforded by these drugs. Angiotensin II receptor antagonists are renoprotective in patients with type 2 diabetes, but studies about their effect in non-diabetic proteinuric nephropathies are very scarce.


METHODS
We randomly assigned 97 patients with non-diabetic nephropathies and proteinuria >1.5 g/24 h to treatment with losartan (50 mg daily) or amlodipine (5 mg daily) for 20 weeks. Doses of the study medications were titrated to achieve a target blood pressure <140/90 mmHg in both groups. Primary outcome was the decrease in the level of 24 h proteinuria. Secondary outcomes were changes in the plasma and urinary levels of TGF-beta.


RESULTS
The baseline characteristics in both groups were similar. Proteinuria decreased by 32.4% (95% confidence interval -38.4 to -21.8%) after 4 weeks of treatment and by 50.4% (-58.9 to -40.2%) after 20 weeks in the losartan group, whereas no significant proteinuria changes were observed in the amlodipine group (P < 0.001). There was no significant correlation between the level of baseline proteinuria and the proteinuria decrease induced by losartan. Both losartan and amlodipine induced a similar and significant blood pressure reduction. Target blood pressure was achieved with the initial dose of study medication (50 mg daily) in 76% of losartan group patients and in 68% of the amlodipine group patients (5 mg daily). Urinary TGF-beta significantly decreased with losartan (-22.4% of the baseline values after 20 weeks of treatment), whereas it tended to increase with amlodipine (between-group difference P < 0.05). A significant correlation between proteinuria decrease and urinary TGF-beta reduction was found in the losartan group (r = 0.41, P < 0.005). Serum creatinine and serum potassium remained stable during the study in both groups.


CONCLUSIONS
Losartan induced a drastic decrease in proteinuria accompanied by a reduction in urinary excretion of TGF-beta in patients with non-diabetic proteinuric renal diseases.
Praga
Manuel
M
Hospital 12 de Octubre, Madrid, Hospital Virgen del Rocio, Sevilla, Hospital Gregorio Marañón, Madrid, Spain. mpragat@senefro.org
Andrade
Carlos Fernández
CF
Luño
José
J
Arias
Manuel
M
Poveda
Rafael
R
Mora
Jose
J
Prat
Marti Valles
MV
Rivera
Francisco
F
Galceran
Jose María
JM
Ara
Jorge Martínez
JM
Aguirre
Román
R
Bernis
Carmen
C
Marín
Rafael
R
Campistol
Jose María
JM
D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003920:Diabetes Mellitus; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy*; D016212:Transforming Growth Factor beta / Q000097:blood; D016896:Treatment Outcome
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D016212:Transforming Growth Factor beta; D017311:Amlodipine; D019808:Losartan