title: Antiproteinuric efficacy of losartan in comparison with amlodipine in non-diabetic proteinuric renal diseases: a double-blind, randomized clinical trial.
abstract: 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.
authors.affiliation: Hospital 12 de Octubre, Madrid, Hospital Virgen del Rocio, Sevilla, Hospital Gregorio Marañón, Madrid, Spain. mpragat@senefro.org
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.forename: Carlos Fernández
authors.initials: CF
authors.lastname: Andrade
authors.forename: José
authors.initials: J
authors.lastname: Luño
authors.forename: Manuel
authors.initials: M
authors.lastname: Arias
authors.forename: Rafael
authors.initials: R
authors.lastname: Poveda
authors.forename: Jose
authors.initials: J
authors.lastname: Mora
authors.forename: Marti Valles
authors.initials: MV
authors.lastname: Prat
authors.forename: Francisco
authors.initials: F
authors.lastname: Rivera
authors.forename: Jose María
authors.initials: JM
authors.lastname: Galceran
authors.forename: Jorge Martínez
authors.initials: JM
authors.lastname: Ara
authors.forename: Román
authors.initials: R
authors.lastname: Aguirre
authors.forename: Carmen
authors.initials: C
authors.lastname: Bernis
authors.forename: Rafael
authors.initials: R
authors.lastname: Marín
authors.forename: Jose María
authors.initials: JM
authors.lastname: Campistol
mesh_terms: 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
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D016212:Transforming Growth Factor beta; D017311:Amlodipine; D019808:Losartan