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Clinical Significance of Renal Function in Hypertensive Patients at High Risk
Results From the INSIGHT Trial
Peter W. de Leeuw, MD, PhD;
Luis M. Ruilope, MD, PhD;
Christopher R. Palmer, PhD;
Morris J. Brown, MD, PhD;
Alain Castaigne, MD, PhD;
Giuseppe Mancia, MD, PhD;
Talma Rosenthal, MD, PhD;
Gilbert Wagener, MD
Arch Intern Med. 2004;164:2459-2464.
Background Increasing evidence suggests renal involvement in hypertension-related cardiovascular and cerebrovascular complications. To assess this role of renal function in more detail, we studied the evolution of renal function and the relationship of renal function with mortality and morbidity in the Intervention as a Goal in Hypertension Treatment (INSIGHT) study.
Methods The INSIGHT study was a double-blind, randomized, multicenter trial in patients with hypertension and at least 1 additional cardiovascular risk factor. Treatment consisted of nifedipine gastrointestinal therapeutic system, 30 mg/d, or hydrochlorothiazide-amiloride (25 mg/d of hydrochlorothiazide and 2.5 mg/d of amiloride hydrochloride). Primary outcome was a composite of cardiovascular death, myocardial infarction, heart failure, and stroke. Renal function was assessed by measuring creatinine clearance, serum creatinine level, and serum uric acid level and by the presence of proteinuria.
Results Creatinine clearance fell more in nifedipine recipients than in hydrochlorothiazide-amiloride recipients. Renal insufficiency developed in 2% of nifedipine recipients and 5% of hydrochlorothiazide-amiloride recipients. Primary outcomes occurred in 15% of patients with increased serum creatinine levels and 6% of patients with normal levels (odds ratio [OR] 2.89; 95% confidence interval [CI], 1.92-4.36; P<.001). Primary outcomes were more likely in patients with low creatinine clearance (<60 mL/min) than in those with higher clearances (9% vs 5%, respectively [OR, 1.51, 95%CI, 1.22-1.88; P<.001]).
Conclusions Renal function is an important predictor of risk in hypertensive patients at high risk. Antihypertensive treatment with a long-acting dihydropyridine calcium channel blocker may better preserve renal function than would treatment with diuretics.
Author Affiliations: Department of Medicine, University Hospital Maastricht, Maastricht, the Netherlands (Dr de Leeuw); Unidad de Hipertension, Hospital 12 de Octobre, University of Madrid, Madrid, Spain (Dr Ruilope); Centre for Applied Medical Statistics (Dr Palmer) and Clinical Pharmacology Unit (Dr Brown), University of Cambridge, Cambridge, England; Hopital Henri-Mondor, Creteil, Paris, France (Dr Castaigne); Cattedra di Medicina Interna, University of Milano-Bicocca, St Gerardo Hospital, Monza, Italy (Dr Mancia); Hypertension Unit, the Chaim Sheba Medical Centre, University of Tel Aviv, Tel Aviv, Israel (Dr Rosenthal); and Bayer AG, Pharma Research Center, Wuppertal, Germany (Dr Wagener).
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