FP368THE ASSOCIATION OF β-BLOCKER USE AND THE PROGRESSION OF RENAL FAILURE IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract

Introduction and Aims: CKD is one of the major risks for CVD. Experimental and clinical studies have suggested that sympathetic overactivity in kidney disease is involved in the genesis of hypertension, the progression of kidney disease, and the cardiac complications among CKD patients. The beta-blocker (BB) is one of the counter-regulatory agents of the sympathetic nerve system, and its clear benefits of mortality reduction among patients with a prior history of CVD have been demonstrated in many clinical trials. However, such evidence in CKD patients without CVD has not yet been established. The aim of this study is to evaluate the association between the use of BB and the progression of kidney disease in CKD patients without CVD. Methods: We used the data from a Japanese longitudinal, observational study (OVIDS-CKD), consisting of 738 predialysis CKD outpatients. Those with medication data but without prior CVDs (n=340) were included in analysis. The prior CVD was defined as a history of stroke, coronary artery disease, heart failure, aortic disease, valvular disease, or peripheral artery disease. The subjects were followed regularly at <3-month intervals. The primary endpoint was a composite of doubling of Cr, initiation of renal RRT, and death. We performed Cox proportional hazards models to estimate the hazards ratio (HR) of BB use at baseline adjusting for other clinical parameters, such as age, gender, eGFR, urinary protein, diabetes, BMI, blood pressure, the number of anti-hypertensive drugs except for BB, administration of ACEI/ARBs, Hb, Alb, corrected Ca, iP, and FGF23. We additionally employed 1:k (k = 1-6) propensity-score full matching, where one treated patient matched to at most k controls. Results: The patients on BB presented significantly-lower eGFR, more prominent proteinuria, higher BMI, use of more anti-hypertensive drugs, lower Alb, higher 1-84 PTH, higher FGF23, and lower 25OHD levels, most of which suggested a poor risk for CVD at baseline. During a median follow-up of 4.4 years, 109 patients reached the primary endpoint. Of those, 12 (11.0%) patients died before RRT, 71 (65.1%) reached a doubling of Cr, and 26 (23.9%) started dialysis. Although the Kaplan Meier curves suggested a worse outcome in BB users (P for log-rank test = 0.0562, unadjusted HR = 1.60 (95% C.I. 0.98 - 2.59)), when a multivariable Cox proportional hazards model was employed only with the variables that were significantly-different between the two groups at baseline, the adjusted HR was 1.58 with a wider confidence interval of 0.86 - 2.90. We also evaluated a fully-adjusted model and a parsimonious model with a stepwise backward-elimination method, both models failed to show statistically significant differences; 1.48 (0.72 - 3.03) and 1.48 (0.82 - 2.61), respectively. The 1:k (k=1-6) full matching using propensity score did not show a significant HR for BB users; adjusted HR = 0.93 (0.52 - 1.68). Conclusions: The BB use was not associated with better or worse renal outcomes in CKD patients without a prior history of CVD. However, because the results might have been inconclusive, confirmation in a larger study should be required.