In Hemodialysis Patients, Physiologic Cholecalciferol Affects Bone, Mineral Biochemistry

By Lorraine L. Janeczko

NEW YORK - Replenishing cholecalciferol in hemodialysis patients can normalize their calcidiol, calcitriol, and calcium levels, new research suggests.

Oral weekly doses of 25,000 International Units (IU) of cholecalciferol for 13 weeks is an effective, safe, inexpensive, and manageable way to increase calcidiol (25-hydroxyvitamin D) and calcitriol (1,25-dihydroxyvitamin D) levels in these patients, the study authors reported online May 22 in the American Journal of Kidney Diseases.

"Many clinicians already know that administering 'supraphysiological' doses of nutritional vitamin D increases calcitriol levels in end-stage kidney disease, including in anephric patients. Our study emphasized the fact that 'physiological' doses of cholecalciferol increased the blood levels of calcitriol in maintenance hemodialysis patients with 25-hydroxyvitamin D insufficiency/deficiency," said lead author Dr. Annick Massart of Erasme Hospital of the Universite Libre de Bruxelles in Brussels, Belgium.

"We were surprised by the observation that nine patients in the placebo group (out of 29) experienced bone fracture episodes while no bone fractures at all were detected in the treatment group. This single observation merits confirmation in bigger prospective studies but already meets the conclusions of previous observational and physiopathology studies," she told Reuters Health by email.

"We suggest that any treatment with active forms of vitamin D be preceded by cholecalciferol repletion above 30 ng/mL," Dr. Massart said.

The authors explain that the 2009 Kidney Disease: Improving Global Outcomes clinical practice guideline suggests restoring calcidiol levels to over 30 ng/mL in patients treated with maintenance hemodialysis, but does not provide a specific treatment protocol.

To learn more, Dr. Massart and colleagues conducted a 13-week double-blind, randomized, controlled trial followed by a 26-week open-label study in two nephrology centers in Belgium. They recruited 55 adult maintenance hemodialysis patients with calcidiol levels under 30 ng/mL.

Eligible patients had chronic kidney disease stage 5 and had been receiving hemodialysis for at least three months with a minimum of three sessions per week.

Patients were excluded if they had vitamin D formulations adjusted one month prior to enrollment, plasma calcium level over 10.2 mg/dL, prior parathyroidectomy, granulomatous disorder, or estimated life expectancy less than one year.

During the first portion of the study, patients were randomly assigned to receive either 25,000 IU of weekly oral cholecalciferol (n=26) or a placebo (n=29). During the following open-label period, patients in both groups received individualized cholecalciferol adjusted to their most recent calcidiol assessment.

The researchers measured blood calcium and phosphate weekly and intact parathyroid hormone (iPTH), calcidiol, calcitriol, and bone turnover markers every three months.

They found the proportion of patients with calcidiol levels 30 ng/mL or higher at 13 weeks was significantly greater in the treatment group compared with the placebo group (61.5% vs. 7.4%; P<0.001), and the proportion of patients achieving the target calcium level in the treatment group was also higher (76.9% vs. 48.2%; P=0.03).

The incidence of hypercalcemia and phosphate and iPTH levels were similar between groups. The open-label study phase did not significantly change the prevalence of calcidiol level 30 ng/mL or higher in patients from the placebo group. No patient had hypervitaminosis D (over 100 ng/mL).

The authors say the small size of their study population was a limitation and suggest further research.

Dr. Janice P. Lea of Emory University School of Medicine in Atlanta, Georgia, told Reuters Health in an email, "Cholecalciferol repletion in dialysis patients has not been the recommended standard of care and has not been addressed by many studies. I believe it may start to change clinical practice and that, with more studies, it will become standard of care."

"We need more conclusive data on cholecalciferol repletion and effects on PTH," Dr. Lea added. A hypertension specialist, she was not involved in the study.

The study was supported by Genzyme-Sanofi and S.M.B. One of the authors has received consulting fees from Amgen, and the rest declared no related conflicts of interest.

SOURCE: https://bit.ly/1pvjOre

Am J Kidney Dis 2014.

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