No iPTH Oversuppression With Extended-Release Calcifediol

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Intact parathyroid hormone levels decline in proportion with SHPT severity in patients taking the drug.
Intact parathyroid hormone levels decline in proportion with SHPT severity in patients taking the drug.
The following article is part of conference coverage from Kidney Week 2017 in New Orleans hosted by the American Society of Nephrology. Renal & Urology News staff will be reporting live on medical studies conducted by nephrologists and other specialists who are tops in their field in acute kidney injury, chronic kidney disease, dialysis, transplantation, and more. Check back for the latest news from Kidney Week 2017.

NEW ORLEANS—Extended-release calcifediol (ERC) reduces intact parathyroid hormone (iPTH) levels gradually, according to secondary hyperparathyroidism (SHPT) severity, with no evidence of oversuppression, researchers reported at the American Society of Nephrology's Kidney Week 2017 meeting.

PTH oversuppression is a significant concern in patients with stage 3-4 CKD treated with calcitriol or its 1α-hydroxylated analogs, as iatrogenic induction of a low PTH level is an independent strong risk factor for adynamic bone disease, fractures and cardiovascular death, the researchers explained.

In a post hoc analysis of double-blind randomized trials, Stuart Sprague, DO, of NorthShore University HealthSystem-University of Chicago, and collaborators examined iPTH suppression over 26 weeks in 429 patients with stage 3-4 chronic kidney disease, vitamin D insufficiency, and iPTH levels above 85 pg/mL who received either ERC (20 or 60 mcg daily) or placebo. According to baseline iPTH divided into tertiles, average iPTH was 98, 130, and 203 pg/mL in the ERC groups and 102, 133, and 201 pg/mL in the placebo groups. Each ERC tertile included 75 patients and each placebo tertile 40-41 patients.

In the ERC groups, average iPTH declined significantly by 18, 28, and 50 pg/mL in tertiles 1, 2, and 3, respectively, over 26 weeks. Suppression of iPTH increased from 19% to 26% of baseline from tertile 1 to 3. No cases of oversuppression were observed.

In addition, total 25-hydroxyvitamin D and total 1,25-dihydroxy vitamin D levels rose similarly in all ERC patients. Any effect of the drug on serum calcium and phosphate appeared minor and did not differ from placebo.

“ERC produced mean absolute iPTH reductions that were proportional to baseline iPTH levels, consistent with a mechanism of action involving physiological regulation of iPTH modulated by SHPT severity,” Dr Sprague told Renal & Urology News.

“These data demonstrate that ERC can be safely used to control hyperparathyroidism in vitamin D deficient patients with CKD stages 3 and 4 and is effective even in patients with the most severe hyperparathyroidism. The use of vitamin D receptor activators, which are associated with hypercalcemia, may not be necessary in this patient population.”

The team next plans to investigate the effect of ERC in patients with advanced kidney disease, especially those undergoing dialysis.

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

Visit Renal & Urology News' conference section for continuous coverage from Kidney Week 2017.


Reference

1. Sprague SM, Strugnell SA, Ashfaq A, et al. PTH Suppression with extended-release Calcifediol (ERC) Is directly proportional to severity of secondary hyperparathyroidism (SHPT). Presented in poster format at Kidney Week 2017 in New Orleans (Oct. 31 to Nov. 5). Abstract TH-PO515.

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