Effect of losartan and amlodipine on proteinuria and transforming growth factor-beta1 in patients with IgA nephropathy.

Abstract

Transforming growth factor-beta1 (TGF-beta1) is the major profibrotic cytokine involved in many renal diseases, and urinary TGF-beta1 reflects intrarenal TGF-beta1 production. Urinary TGF-beta1 excretion is reported to be significantly increased in patients with immunoglobulin A (IgA) nephropathy. The aim of the present study was to compare the effects of losartan and amlodipine on proteinuria, as well as on serum and urine TGF-beta1 levels in IgA nephropathy patients with hypertension and proteinuria. The initial 4 week washout period was followed by 12 weeks of active treatment, in which patients were randomized to once-daily treatment with losartan 50 mg (group 1, n=20) or amlodipine 5 mg (group 2, n=16). Urinary protein and TGF-beta1 excretion, serum TGF-beta1 and other clinical parameters were determined at baseline and during 12 weeks of active treatment. Both treatments controlled blood pressure (BP) to a similar degree, and renal function and other biochemical parameters did not change during the study period. Urinary protein and TGF-beta1 excretions were significantly elevated in IgA nephropathy patients. Losartan significantly reduced urinary protein (from 2.3+/-1.5 g/day at baseline to 1.2+/-1.5 g/day at 12 weeks, P<0.05) and urinary TGF-beta1 excretion (from 31.2+/-14.0 pg/mg creatinine at baseline to 22.1+/-13.5 pg/mg creatinine at 12 weeks, P<0.05). In contrast, amlodipine had no affect on urinary protein and TGF-beta1 excretion. Both losartan and amlodipine failed to reduce serum TGF-beta1 levels. Losartan and amlodipine, with similar control of BP, showed different effects on urine protein or TGF-beta1 excretion. Whereas losartan improved both urinary parameters, amlodipine did not. These differences might be important for the management of IgA nephropathy.