CKD: Does Vitamin D Improve LV Mass and Function:

Angela Yee-Moon Wang, MD, PhD  Department of Medicine, Queen Mary Hospital University of Hong Kong, Hong Interview with:
Angela Yee-Moon Wang, MD, PhD

Department of Medicine, Queen Mary Hospital
University of Hong Kong, Hong Kong What are the main findings of the study?

Dr. Wang: The OPERA Trial is a prospective, double-blind, randomized placebo-controlled trial aiming to determine whether oral activated vitamin D, paricalcitol, reduces left ventricular (LV) mass in stages 3 -5 CKD patients with LV hypertrophy.

Primary endpoint of the study was change in cardiac magnetic resonance imaging estimated LV mass index over 52 weeks. Secondary endpoints included changes in LV volume, echocardiographic measures of systolic and diastolic function, biochemical parameters of mineral bone disease, 24-hour urine protein and estimated glomerular filtration rate.

Our results showed that 52-week treatment with oral paricalcitol 1µg daily significantly improved secondary hyperparathyroidism but did not reduce LV mass and volume, or improve systolic and diastolic dysfunction in stages 3-5 CKD patients. Our findings are confirmatory to the PRIMO study showing that 48-week therapy with paricalcitol did not alter LV mass index or diastolic dysfunction in patients with CKD. It is important to point out some key differences between the OPERA study and PRIMO study in that the LV mass index of the OPERA study subjects was at least 70% higher than that in PRIMO Study with a large proportion of subjects exhibited diastolic dysfunction. In addition, OPERA’s study subjects had more severe CKD and secondary hyperparathyroidism as compared to PRIMO study. Furthermore, the dose of paricalcitol used in our study was half of that in PRIMO study but was already sufficient in suppressing iPTH and alkaline phosphatase in ≥ 70% of the CKD subjects, suggesting potential racial differences in the responsiveness to activated vitamin D therapy.


                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Were any of the findings unexpected?

Dr. Wang: As part of the adverse events monitoring, we observed significantly lower rates of cardiovascular-related hospitalizations in paricalcitol-treated group as compared to placebo group This observation was rather unexpected, given that our sample size (adequately powered for primary endpoint) was small and not powered to examine hard outcomes. This made our preliminary observation even more significant. Our findings are in keeping with the PRIMO study showing also significantly lower incidence of cardiovascular-related hospitalizations and fewer hospitalization days among paricalcitol-treated patients compared to placebo-treated patients. However, we cautioned that our observations can only be considered hypothesis generating, given the small sample size. The mechanisms by which oral activated vitamin D reduced cardiovascular-related hospitalizations are currently unclear. We speculate that paricalcitol may exert cardioprotective effect by reducing left atrial volume and N-terminal-pro-brain natriuretic peptide as reported in the post-hoc analysis of PRIMO study or may exert vascular benefit and this would require further investigations. What should clinicians and patients take away from this study?

Dr. Wang: Treatment with oral activated vitamin D treatment, paricalcitol, at 1µg daily for 1 year is highly effective in controlling secondary hyperparathyroidism but does not retard cardiac hypertrophy or improve cardiac dysfunction in patients with stages 3 -5 CKD. What recommendations do you have for future research as a result of your study?

Dr. Wang: We believe further prospective, adequately powered follow-up study is needed to determine if activated vitamin D treatment may improve survival and cardiovascular outcomes in patients with chronic kidney disease.


JASN ASN.2013010103; published ahead of print September 19, 2013, doi:10.1681/ASN.2013010103

Angela Yee-Moon Wang, Fang Fang, John Chan, Yue-Yi Wen, Shang Qing, Iris Hiu-Shuen Chan, Gladys Lo, Kar-Neng Lai, Wai-Kei Lo, Christopher Wai-Kei Lam, and Cheuk-Man Yu

JASN ASN.2013010103; published ahead of print September 19, 2013, doi:10.1681/ASN.2013010103

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Not for specific medical advice. Please consult your physician for recommendations and questions. Editor: Marie Benz