Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy

In diabetic nephropathy, angiotensin-converting-enzyme (ACE) inhibitors have a greater effect than other antihypertensive drugs on proteinuria and the progressive decline in glomerular filtration rate (GFR). Whether this difference applies to progression of non-diabetic proteinuric nephropathies is...

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Bibliographic Details
Published in:The Lancet (British edition) 1997-06, Vol.349 (9069), p.1857-1863
Main Author: The GISEN Group
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blood pressure
Diabetes
Drug therapy
Kidneys
Medical research
Medical sciences
Pharmacology. Drug treatments
Urinary system
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Summary:In diabetic nephropathy, angiotensin-converting-enzyme (ACE) inhibitors have a greater effect than other antihypertensive drugs on proteinuria and the progressive decline in glomerular filtration rate (GFR). Whether this difference applies to progression of non-diabetic proteinuric nephropathies is not clear. The Ramipril Efficacy In Nephropathy study of chronic non-diabetic nephropathies aimed to address whether glomerular protein traffic influences renal-disease progression, and whether an ACE inhibitor was superior to conventional treatment, with the same blood-pressure control, in reducing proteinuria, limiting GFR decline, and preventing endstage renal disease. In this prospective double-blind trial, 352 patients were classified according to baseline proteinuria (stratum 1: 1–3 g/24 h; stratum 2: ≥3 g/24 h), and randomly assigned ramipril or placebo plus conventional antihypertensive therapy targeted at achieving diastolic blood pressure under 90 mm Hg. The primary endpoint was the rate of GFR decline. Analysis was by intention to treat. At the second planned interim analysis, the difference in decline in GFR between the ramipril and placebo groups in stratum 2 was highly significant (p=0·001). The Independent Adjudicating Panel therefore decided to open the randomisation code and do the final analysis in this stratum (stratum 1 continued in the trial). Data (at least three GFR measurements including baseline) were available for 56 ramipril-assigned patients and 61 placebo-assigned patients. The decline in GFR per month was significantly lower in the ramipril group than the placebo group (0·53 [0·08] vs 0·88 [0·13] mL/min, p=0·03). Among the ramipril-assigned patients, percentage reduction in proteinuria was inversely correlated with decline in GFR (p=0·035) and predicted the reduction in risk of doubling of baseline creatinine or endstage renal failure (18 ramipril vs 40 placebo, p=0·04). The risk of progression was still significantly reduced after adjustment for changes in systolic (p=0·04) and diastolic (p=0·04) blood pressure, but not after adjustment for changes in proteinuria. Blood-pressure control and the overall number of cardiovascular events were similar in the two treatment groups. In chronic nephropathies with proteinuria of 3 g or more per 24 h, ramipril safely reduces proteinuria and the rate of GFR decline to an extent that seems to exceed the reduction expected for the degree of blood-pressure lowering.
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(96)11445-8