Add-on angiotensin II receptor blockade lowers urinary transforming growth factor-β levels

Abstract Progression of renal failure, despite renoprotection with angiotensin-converting enzyme (ACE) inhibitors in patients with proteinuric nephropathies, may be caused by persistent renal production of transforming growth factor-β1 (TGF-β1) through the angiotensin II subtype 1 (AT1) receptors. We tested the hypothesis that AT1-receptor blocker therapy added to a background of chronic maximal ACE inhibitor therapy will result in a reduction in urinary TGF-β1 levels in such patients. Sixteen patients completed a two-period, crossover, randomized, controlled trial, details of which have been previously reported. All patients were administered lisinopril, 40 mg/d, with either losartan, 50 mg/d, or placebo. Blood pressure (BP) was measured using a 24-hour ambulatory BP monitor. Overnight specimens of urine were analyzed for urine TGF-β1, protein, and creatinine concentrations. Mean age of the study population was 53 ± 9 (SD) years; body mass index, 38 ± 5.7 kg/m 2 ; seated BP, 156 ± 18/88 ± 12 mm Hg; and urine protein excretion, 3.6 ± 0.71 g/g of creatinine. Twelve patients had diabetic nephropathy, and the remainder had chronic glomerulonephritis. At baseline, urinary TGF-β1 levels were significantly increased in the study population compared with healthy controls (13.2 ± 1.2 versus 1.7 ± 1.1 ng/g creatinine; P r 2 = 0.53; P = 0.001), as well as systolic BP and urinary TGF-β1 level ( r 2 = 0.57; P 2002 by the National Kidney Foundation, Inc.