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Randomized controlled trial: lisinopril reduces proteinuria, ammonia, and renal polypeptide tubular catabolism in patients with chronic allograft nephropathy.

Author(s): Amara AB, Sharma A, Alexander JL, Alfirevic A, Mohiuddin A, Pirmohamed M, Close GL, Grime S, Maltby P, Shawki H, Heyworth S, Shenkin A, Smith L, Sharma AK, Hammad A, Rustom R

Affiliation(s): Pathophysiology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom.

Publication date & source: 2010-01-15, Transplantation., 89(1):104-14.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Angiotensin-converting enzyme inhibitors in native nephropathies reduce proteinuria and delay progression to renal failure. Data in renal transplantation remain limited. A negative effect on glomerular filtration rate was concluded in a recent systematic review. METHODS: In this novel randomized controlled trial, 47 patients with chronic allograft nephropathy, severe renal impairment, and more than or equal to 1 g/24 hr proteinuria were randomized to lisinopril (group A) or other hypotensives (group B) for 1 year. Sodium bicarbonate was given to all patients to treat metabolic acidosis prophylactically (acidosis increases significantly with lisinopril). The annual rate of decline of graft function was measured isotopically (primary outcome) and 24 hr proteinuria, genotyping, radiolabeled polypeptide aprotinin proximal tubular catabolic studies (in group A only) as secondary outcome measurements were undertaken. RESULTS: At baseline, groups were comparable except for greater proteinuria in group A. After 1 year, the rate of decline of graft function and graft survival were comparable in both groups. Proteinuria decreased significantly in group A patients only. Lisinopril also significantly reduced radiolabeled aprotinin uptake and metabolism, plasma aldosterone, and ammonia excretion. Plasma potassium, bicarbonate, and mean arterial pressures were comparable in both groups. Patients with more than or equal to 30% reduction in proteinuria had a significant association with rs699 polymorphism in the angiotensinogen gene. CONCLUSIONS: The rate of decline of renal graft function in patients with chronic allograft nephropathy was not adversely affected by lisinopril therapy given for 1 year. Lisinopril significantly reduced proteinuria, renal proximal tubular polypeptide catabolism, plasma aldosterone, and ammonia excretion suggesting relative preservation of graft function. Treating metabolic acidosis allowed safe and prolonged use of angiotensinogen-converting enzyme inhibitors.

Page last updated: 2010-10-05

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