LBSAT131 Extended-release Calcifediol Reduced Ipth And Normalized 1,25-dihydroxyvitamin D In Esrd.

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Abstract Background Extended-release calcifediol (ERC) has been shown in randomized clinical trials to effectively and safely treat secondary hyperparathyroidism (SHPT) in adults with stage 3-4 chronic kidney disease (CKD) and vitamin D insufficiency when administered at 210 or 420 mcg per week (30 or 60 mcg/day), doses which gradually raise serum total 25-hydroxyvitamin D (25D) to mean steady-state levels of 50-56 ng/mL. Clinical Case A 41-year-old male Caucasian with end-stage renal disease (ESRD) requiring regular hemodialysis (HD) experienced an overdose during participation in a phase 2 study of ERC for treating SHPT. Medical history included hypertension, type II diabetes, glomerulonephritis, bilateral lower extremity edema, muscle cramps, pruritus, shortness of breath, sporadic hypercalcemia and hyperphosphatemia, and iron deficiency anemia. Treatment with ERC began at an incorrect dosage of 2,700 mcg per week (900 mcg per HD) for 10 weeks as the study coordinator misunderstood the protocol-specified dose of 900 mcg per week. A 2.5% calcium dialysate was used during the study. Serum 25D gradually increased from 19 to 339 ng/mL (32-100), serum total 1,25-dihydroxyvitamin D (1,25D) increased from 6.3 to 137 pg/mL (24-86), plasma iPTH decreased from 440 to 146 pg/mL (15-65), and corrected serum calcium (Ca) decreased from 9.3 to 9.1 mg/dL (8.6-10.4). The subject remained asymptomatic throughout. Discovery of the overdose was delayed due to limited monitoring access during the pandemic and occurred when the ERC supply was prematurely exhausted. A physical exam and retrospective review of study records were promptly undertaken with no abnormalities noted. ERC administration, after a 1-dose hiatus, resumed at the correct dose (900 mcg per week). Serum 25D decreased over the next 4 weeks to 251 ng/mL, 1,25D decreased to 46. 0 pg/mL, iPTH increased to 186 pg/mL, and Ca remained stable (9. 0 mg/dL). The subject completed the full 6-month treatment period without adverse events. Clinical Lessons Gradual elevation of serum 25D and 1,25D with ERC to high levels had no impact on serum Ca or adverse events in the described subject suggesting that hypercalcemia observed with other vitamin D therapies used during HD results from abrupt increases in these metabolites. Serum 1,25D normalized with 25D elevation despite the lack of functional kidneys, indicating that extra-renal 1,25D production can become sufficient to control increased iPTH in ESRD when serum 25D is elevated well above the current clinical practice target of 30 ng/mL. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

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