High-dose extended-release calcifediol successfully treated advanced secondary hyperparathyroidism in an end-stage kidney disease patient: a case report

Background: This unprecedented case report supports three important conclusions pertinent to the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD): (1) serum 25-hydroxyvitamin D (25D) repletion can effectively reduce elevated intact parathyroid hormone (iPTH) in advanced CKD; (2) serum total 25D levels required for effective iPTH reduction are much higher than currently recommended targets of 20 or 30 ng/mL; and, (3) published estimates of serum 25D toxicity thresholds are probably low. Case presentation: A 41-year-old Caucasian male requiring regular hemodialysis (HD) was overdosed with 900 (rather than 300) µg/HD of extended-release calcifediol (ERC) for 10 weeks in an investigational trial. When the overdosing was recognized, serum 25D had increased 18-fold (from 19 to 339 ng/mL), 1,25-dihydroxyvitamin D (1,25D) had risen 23-fold (from 6 to 137 pg/mL), and iPTH had decreased by 67% (from 440 to 146 pg/mL) with no impact on calcium or phosphorus and no adverse events noted. Conclusions: These observations indicate that effective management of SHPT in advanced CKD is possible with effective vitamin D depletion therapy, a discovery that potentially enables an important and long overdue change to the current paradigm for treating SHPT in ESKD: the seemingly inevitable use of calcitriol or 1a-hydroxylated vitamin D analogs and the associated risk of vascular calcification may be avoided altogether by harnessing substate-driven 1,25D production in non-renal tissues expressing CYP27B1.