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Vitamin D receptor activation and left ventricular hypertrophy in advanced kidney disease

Thadhani R*; Appelbaum E; Chang Y; Pritchett Y; Bhan I; Agarwal R; Zoccali C; Wanner C; Lloyd Jones D; Cannata J; Thompson T; Audhya P; Andress D; Zhang W; Ye J; Packham D; Singh B; Zehnder D; Manning W J; Pachika A; Solomon S D
Scopus
Harvard Medical School; NorthwesternUniversity; Indiana university School of medicine; Feinberg School of Medicine; Indiana University School of Medicine; Harvard medical school; NorthWestern University; NORTHWESTERN UNIVERSITY; harvard medical school; Beth Israel Deaconess Medical Center, Harvard; United States

摘要

Background: In chronic kidney disease (CKD), left ventricular hypertrophy (LVH) is prevalent and is associated with increased cardiovascular morbidity and mortality. Vitamin D receptor (VDR) activation attenuates LVH progression in animal models. Methods: PRIMO is a multinational, randomized, double-blinded trial with oral paricalcitol in subjects with stages 3-4 CKD, mild-to-moderate LVH and an LV ejection fraction >50%. The primary endpoint is change in the left ventricular mass index (LVMI) compared with placebo after 48 weeks of treatment. The main secondary endpoints are changes in diastolic function parameters. In this paper, we report baseline characteristics from this study. Results: LVMI was 33.0 ± 7.5 g/m2.7 for males and 30.8 ± 7.2 g/m2.7 for females (p = 0.04). LVMI correlated with systolic blood pressure (r = 0.24), urine albumin creatinine ratio (r = 0.39), troponin T (r = 0.29), high-sensitivity C-reactive protein (r = 0.25) and plasma levels of B-type brain natriuretic peptide (r = 0.22); all p < 0.01. In multiple linear regression, each remained independently associated with LVMI. The early diastolic velocity of the lateral mitral annulus (E';) was 8.1 ± 2.4 cm/s. E'; was inversely correlated with age in univariate (r = -0.14, p = 0.04) and multivariable (p = 0.02) analysis. Conclusion: Among 227 multinational subjects with stages 3-4 CKD, baseline LVMI correlates with baseline blood pressure, urine albumin creatinine ratio and cardiac biomarkers, and baseline diastolic function correlates with age. This research was funded by Abbott Laboratories; ClinicalTrials.gov No. NCT00497146.

关键词

Chronic kidney disease Left ventricular hypertrophy Vitamin D receptor