We thank Dr. Nwaohiri1 for commenting on our work and agree with the statement that the jury is still out about the consistency of the effect of vitamin D supplementation on vascular function in CKD. Vascular disease in CKD is multifactorial, and the effect of a single intervention will be affected by a variety of patient-related factors as well as study-related factors.
Some important differences between our study and the study by Kendrick et al.2 could explain the differential findings. In addition to a younger population, a lower proportion of smokers, and exclusion of patients with diabetes, our population was more vitamin D deficient (13.2±4.8 ng/ml [placebo] and 13.4±4.4 ng/ml [cholecalciferol] in our study versus 21.7±7.7 ng/ml [calcitriol] and 23±7.6 ng/ml [cholecalciferol] in the study by Kendrick et al.2) and received a higher cholecalciferol dose (5000 versus 2000 IU/d). Importantly, the rise in 25(OH)D and the final achieved levels were greater in the group that received cholecalciferol in our study (mean change: 24.9 versus 11 ng/ml). Furthermore, Kendrick et al.2 did not notice any change in another important biologic effect of vitamin D: that on parathyroid hormone. It can be speculated that the rise in circulating 25(OH)D level was not enough to lead to significant biologic effect.
Although the uncertainty about the effect of vitamin D on vascular end points remains, evidence in favor of the beneficial effect of correcting vitamin D deficiency in CKD—including the positive effect on cardiovascular health—is growing. Observational studies and clinical trials have documented favorable modulation of vascular and endothelial function after supplementation with native or activated forms of vitamin D.3,4 In our study, the cholecalciferol-treated patients also experienced a favorable decrease in pulse wave velocity. Similar results were reported in another recent randomized, placebo-controlled clinical trial.5 In this study, patients who achieved the highest 25(OH)D levels were the ones with greatest decreases in pulse wave velocity. Also worth noting is that vitamin D supplementation has been generally safe.
Rather than persist with the one size fits all approach, studies are needed to figure out appropriate patient populations, optimal threshold, preferred formulation, and dose and target levels for vitamin D supplementation and evaluate the effects on hard cardiovascular end points so that our patients can derive the benefits from correction of the vitamin D deficiency.
Disclosures
None.
Acknowledgments
This work was supported by a grant from the Department of Biotechnology, Government of India (grant BT/PR3150/MED/30/640/2011).
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
References
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