Nephrol Dial Transplant (2003) 18: 1806-1813
© 2003 European Renal Association-European Dialysis and Transplant Association
Antiproteinuric efficacy of losartan in comparison with amlodipine in non-diabetic proteinuric renal diseases: a double-blind, randomized clinical trial
1 Hospital 12 de Octubre, Madrid, 2 Hospital Virgen del Rocio, Sevilla, 3 Hospital Gregorio Marañón, Madrid, 4 Hospital Marques de Valdecilla Santander, 5 Hospital de Bellvitge, Barcelona, 6 Fundación Puigvert, Barcelona, 7 Hospital Josep Trueta, Gerona, 8 Hospital General de Alicante, 9 Hospital de Palamos (Gerona), 10 Hospital La Paz, Madrid, 11 Hospital de Galdakano, Vizcaya, 12 Hospital de la Princesa, Madrid, 13 Hospital Central de Asturias and 14 Hospital Clínico y Provincial, Barcelona, Spain
Correspondence and offprint requests to: Dr Manuel Praga, Servicio de Nefrología, Hospital 12 de Octubre, Carretera de Andalucía, Km 5,400, 28041 Madrid, Spain. Email: mpragat{at}senefro.org
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-ß (TGF-ß), 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-ß.
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-ß 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-ß 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-ß in patients with non-diabetic proteinuric renal diseases.
Keywords: angiotensin II blockade; losartan; progression of renal disease; proteinuria; transforming-growth factor-ß (TGF-ß)
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