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Vitamin D Receptor Activation and Left Ventricular Hypertrophy in Advanced Kidney Disease

Thadhani R.a · Appelbaum E.b · Chang Y.a · Pritchett Y.c · Bhan I.a · Agarwal R.d · Zoccali C.e · Wanner C.f · Lloyd-Jones D.g · Cannata J.h · Thompson T.a · Audhya P.c · Andress D.c · Zhang W.c · Ye J.a · Packham D.i · Singh B.j · Zehnder D.k · Manning W.J.b, l · Pachika A.m · Solomon S.D.m
aDivision of Nephrology, Department of Medicine, Massachusetts General Hospital and bPERFUSE CMR Core Laboratory and Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass., cAbbott Laboratories, Abbott Park, Ill., dDepartment of Medicine, Indiana University School of Medicine, Indianapolis, Ind., USA; eNephrology, Dialysis and Transplantation Unit and CNR-IBIM Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy; fDivision of Nephrology, Department of Medicine, University Hospital, University of Wuerzburg, Wuerzburg, Germany; gDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., USA; hServicio de Metabolismo Óseo y Mineral, Hospital Universitario Central de Asturias, Oviedo, Spain; iMelbourne Renal Research Group, Reservoir Private Hospital, Department of Nephrology, Royal Melbourne Hospital, Department of Nephrology, Austin Hospital, Melbourne, Vic., Australia; jSouthwest Kidney Institute, Tempe, Ariz., USA; kClinical Sciences Research Institute, Warwick Medical School, The University of Warwick, Coventry, UK; lDepartment of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, and mCardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass., USA Am J Nephrol 2011;33:139–149 (DOI:10.1159/000323551)

Abstract

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.

 

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