Influence of renal dysfunction phenotype on mortality in the setting of cardiac dysfunction: analysis of three randomized controlled trials.

Pubmed ID: 21926073

Pubmed Central ID: PMC3200208

Journal: European journal of heart failure

Publication Date: Nov. 1, 2011

Affiliation: Department of Medicine, Cardiovascular Division, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. jeffrey.testani@uphs.upenn.edu

MeSH Terms: Humans, Male, Adult, Female, Aged, Cohort Studies, Middle Aged, Randomized Controlled Trials as Topic, Heart Failure, Prognosis, Retrospective Studies, Renal Insufficiency, Glomerular Filtration Rate, Phenotype

Grants: T32 HL007843, 5T32HL007843-15, K23 DK080132, R01 HL088577

Authors: Testani JM, Kimmel SE, Shannon RP, Coca SG, Cappola TP

Cite As: Testani JM, Coca SG, Shannon RP, Kimmel SE, Cappola TP. Influence of renal dysfunction phenotype on mortality in the setting of cardiac dysfunction: analysis of three randomized controlled trials. Eur J Heart Fail 2011 Nov;13(11):1224-30. Epub 2011 Sep 15.

Studies:

Abstract

AIMS: Renal neurohormonal activation leading to a reduction in glomerular filtration rate (GFR) has been suggested as a mechanism for renal insufficiency (RI) in the setting of heart failure. We hypothesized that RI occurring in the presence of renal neurohormonal activation may be prognostically more important than RI in the absence of renal neurohormonal activation. METHODS AND RESULTS: Subjects in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial (n = 429), Beta-Blocker Evaluation of Survival Trial (BEST) (n = 2691), and Studies Of Left Ventricular Dysfunction (SOLVD) trial (n = 6782) limited datasets were studied. The blood urea nitrogen to creatinine ratio (BUN/Creatinine) was employed as a surrogate for renal neurohormonal activation and the primary outcome was the interaction between BUN/Creatinine and RI associated mortality. Baseline RI (GFR < 60 mL/min/1.73 m²) was associated with mortality in all study populations (P < 0.001). In patients with higher BUN/Creatinine, the risk of mortality was consistently greater in patients with RI [adjusted hazard ratio (HR) ESCAPE = 2.8, 95% confidence interval (CI) 1.3-14.3, P = 0.019; BEST = 1.6, 95% CI 1.2-2.2, P = 0.002; SOLVD = 1.6, 95% CI 1.3-2.0, P = 0.001]. However, in patients with lower BUN/Creatinine, the risk of mortality was not elevated in patients with RI (adjusted HR ESCAPE = 0.94, 95% CI 0.35-2.4, P = 0.90, P interaction = 0.005; BEST = 0.97, 95% CI 0.64-1.4, P = 0.90, P interaction = 0.02; SOLVD = 1.0, 95% CI 0.8-1.3, P = 0.71, P interaction = 0.005). CONCLUSION: The association between RI and poor survival observed in heart failure populations appears to be contingent not simply on the presence of a reduced GFR, but possibly on the mechanism by which GFR is reduced.