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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study.

BACKGROUND: Clinical trials of nephropathy in people with type 2 diabetes mellitus have not examined the effects of systolic blood pressure (SBP) or pulse pressure (PP) on the time to end-stage renal disease (ESRD) or death. OBJECTIVES: To evaluate the impact of baseline and treated SBP, diastolic blood pressure (DBP), and PP on composite and individual outcomes including doubling of serum creatinine, ESRD, or death in participants of the Reduction of Endpoints in NIDDM (non-insulin-dependent diabetes mellitus) With the Angiotensin II Antagonist Losartan (RENAAL) Study; to assess the specific effect of the angiotensin receptor blocker losartan potassium on composite and renal outcomes; and to explore the implications of dihydropyridine calcium channel blockers as concurrent therapy on composite and renal outcomes. DESIGN: A Cox proportional hazards regression model was used to assess the hazard risk profile of baseline SBP (categories: <130, 130-139, 140-159, 160-179, and > or =180 mm Hg), DBP (categories: <70, 70-79, 80-89, 90-99, and > or =100 mm Hg), and PP (categories: <60, 60-69, 70-79, 80-89, and > or =90 mm Hg) on renal outcomes. PARTICIPANTS: The study comprised 1513 participants with established nephropathy and hypertension associated with type 2 diabetes. INTERVENTIONS: The RENAAL study was a randomized, placebo-controlled study of losartan vs placebo, with other agents added to achieve the goal of a trough BP (ie, BP immediately prior to the next dosing) below 140/90 mm Hg, and had a mean follow-up of 3.4 years. MAIN OUTCOME MEASURES: The primary analysis was time to composite end point of doubling of serum creatinine, ESRD, or death. RESULTS: A baseline SBP range of 140 to 159 mm Hg increased risk for ESRD or death by 38% (P =.05) compared with those below 130 mm Hg. In a multivariate model, every 10-mm Hg rise in baseline SBP increased the risk for ESRD or death by 6.7% (P =.007); the same rise in DBP decreased the risk by 10.9% (P =.01) when adjusting for urinary albumin-creatinine ratio, serum creatinine, serum albumin, hemoglobin, and hemoglobin A1c. Those randomized to the losartan group with a baseline PP above 90 mm Hg had a 53.5% risk reduction for ESRD alone (P =.003) and a 35.5% risk reduction for ESRD or death (P =.02) compared with the placebo group. CONCLUSIONS: Baseline SBP is a stronger predictor than DBP of renal outcomes in those with nephropathy resulting from type 2 diabetes. Those with the highest baseline PP have the highest risk for nephropathy progression but also garner the greatest risk reduction with SBP lowered to less than 140 mm Hg.[1]


  1. Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study. Bakris, G.L., Weir, M.R., Shanifar, S., Zhang, Z., Douglas, J., van Dijk, D.J., Brenner, B.M. Arch. Intern. Med. (2003) [Pubmed]
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