Patients with stage 3 to 4 chronic kidney disease (CKD) patients with vitamin D insufficiency may need to achieve higher levels of mean serum 25-hydroxyvitamin D than the 20 or 30 ng/mL currently recommended to control secondary hyperparathyroidism (SHPT), according to researchers.

Stephen A. Strugnell, PhD, of OPKO Health in Miami, and colleagues conducted a secondary analysis of pooled data from 2 randomized controlled 26-week trials of extended-release calcifediol (30 to 60 μg). The 429 patients had stage 3 or 4 CKD, elevated intact parathyroid hormone (iPTH, 85 to less than 500 pg/mL), and vitamin D insufficiency (serum total 25-hydroxyvitamin D of 10 to less than 30 ng/mL. Per protocol, patients had serum calcium and phosphorus within normal ranges.

According to results in the American Journal of Nephrology, as mean serum 25-hydroxyvitamin D rose from 13.9 to 92.5 ng/mL (quintile 1 to 5) following treatment, serum 1,25-dihydroxyvitamin D also increased, independent of patients’ CKD stage. The investigators observed concurrent decreases in iPTH and bone turnover markers. But iPTH suppression did not occur until serum 25-hydroxyvitamin D increased to at least 50.8 ng/mL.

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“ERC therapy produced exposure-dependent reductions in plasma iPTH and bone turnover markers only when mean serum total 25-hydroxyvitamin D reached at least 50.8 ng/mL, indicating that current targets for vitamin D repletion therapy in CKD are too low,” Dr Strugnell and the team stated.

Despite a warning by the Institute of Medicine not to increase serum total 25-hydroxyvitamin D levels above 50 ng/mL, no significant adverse changes occurred in the highest quintile of serum 25-hydroxyvitamin D (92.5 ng/mL). Mean serum calcium, phosphorus, fibroblast growth factor 23 (FGF23), estimated glomerular filtration rate (eGFR), and urine calcium to creatinine ratio in quintile 5 did not differ significantly from quintile 1.

“Together these findings suggest that ERC may represent a new effective therapy for treatment of vitamin D deficient SHPT, and imply a need to reevaluate the currently recommended thresholds that define vitamin D sufficiency in CKD patients,” Anders Berg, MD, PhD, and Ravi Thadhani, MD, MPH, of Cedars-Sinai Medical Center in Los Angeles, commented in an accompanying editorial. They added that it remains unknown whether complete normalization of PTH is an appropriate goal for vitamin D repletion. Higher doses of vitamin D supplementation may carry risks, such as hypercalcemia. Patients in these trials were carefully selected, so results cannot be generalized to all CKD patients.

The study was funded by OPKO, the makers of Rayaldee® (calcifediol).

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Strugnell SA, Sprague SM, Ashfaq A, et al. Rationale for raising current clinical practice guideline target for serum 25-hydroxyvitamin D in chronic kidney disease. Am J Nephrol. DOI: 10.1159/000499187

Berg AH, Thadhani RI. Aiming too low: Reevaluation of target concentrations of serum 25-hydroxyvitamin D in secondary hyperparathyroidism. Am J Nephrol. 2019;49:281–283. DOI: 10.1159/000499160