Cholecalciferol supplementation may aid in cardiovascular health for patients on dialysis
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Patients on hemodialysis who received cholecalciferol supplementation for 12 weeks experienced increases a-klotho levels, results of a randomized placebo-controlled trial showed.
According to Jalal Etemadi, MD, of the Kidney Research Center at Tabriz University of Medical Sciences in Iran, and colleagues, this finding suggests supplementation may provide cardiovascular benefits to patients who also have hypovitaminosis D because “vitamin D-fibroblast growth factor-23-klotho forms an axis that takes part ... in cardiovascular complications in patients with chronic kidney disease.”
Defining klotho as “a single-pass transmembrane protein which, mainly expressed in the kidney, appears to modulate aging,” the researchers wrote that serum klotho levels begin decreasing in the early stages of chronic kidney disease and have been shown to be lower in individuals receiving hemodialysis than in those without kidney disease.
“There are growing evidence that low levels of a-Klotho were related to adverse cardiovascular outcomes, all-cause mortality rates, atherosclerosis, increased interventricular septal thickness, cerebrovascular disease, and higher coronary artery calcification score in patients receiving maintenance hemodialysis,” they wrote. “In keeping with these observations, it has been shown that upregulation of Klotho expression by inhibition of mTOR signaling protects against chronic renal failure-related vascular calcification. These potential associations make a-klotho an attractive therapeutic intervention.”
To investigate, Etemadi and colleagues randomized 86 patients to receive either 50,000 IU of cholecalciferol or placebo every week for 12 weeks. All patients were on thrice-weekly hemodialysis and had serum 25(OH)D levels less than 30 ng per mL; at baseline, serum 25(OH)D levels were significantly lower for patients in the treatment arm vs. those receiving placebo.
After the intervention, researchers observed decreases in FGF23 levels and increases in a-klotho levels for patients receiving cholecalciferol supplementation compared with placebo, though only “the before-after difference in a-klotho levels reached statistical significance.”
Further, results suggested 25 (OH) D levels rose for patients receiving supplementation, becoming significantly higher than those receiving placebo after the 12-week intervention. In addition, 60.86% of patients receiving supplementation achieved the “optimal level” of serum 25 (OH) D (ie, more than 30 ng per mL) after 12 weeks.
“Our study adds to the current literature suggesting that cholecalciferol supplementation increases a-klotho levels in the serum of [kidney failure] KF patients undergoing hemodialysis. This may suggest that patients receiving maintenance hemodialysis can benefit from using cholecalciferol supplementation and increase in serum a-klotho levels,” Etemadi and colleagues concluded. “This finding might shed light on our understanding to determine the mechanism whether nutritional cholecalciferol supplementation decelerate the development and progression of vascular calcification and mortality in the patients undergoing chronic hemodialysis. In this field, additional investigation is warranted.”
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