LBSAT229 Extended-release Calcifediol Effectively Raised 25-hydroxyvitamin D In CKD Despite Obesity

Inadequate levels of serum total 25-hydroxyvitamin D (25D) in chronic kidney disease (CKD) are associated with an increased risk of secondary hyperparathyroidism (SHPT). Serum 25D can be difficult to raise sufficiently with vitamin D supplements (cholecalciferol or ergocalciferol) to effectively lower elevated parathyroid hormone (PTH) levels especially in overweight patients. Obesity is common in CKD and requires attention when vitamin D repletion is considered. Vitamin D supplements are fat-soluble molecules which accumulate in adipose tissue. They have low affinity for serum vitamin D binding protein and are poorly mobilized from adipose tissue into circulation for hepatic activation. Recent studies suggest that serum 25D levels of ≥50 ng/mL are necessary to produce significant PTH reductions in nondialysis patients. Data were analyzed from two identical randomized clinical trials investigating the efficacy and safety of treating adult nondialysis patients with extended-release calcifediol (ERC; n=285) or placebo (n=144) to see if ERC raised 25D to at least 50 ng/mL in all body weight categories, with subgroup analyses by race, gender and age. On enrollment, subjects had eGFR of ≥15 and <60 mL/min/1.73 m2, PTH ≥85 and <500 pg/mL, serum 25D ≥10 and <30 ng/mL, corrected serum calcium ≥8.4 and <9.8, serum phosphorus ≥2. 0 and <5. 0, absence of nephrotic range proteinuria (>3 mg/mg creatinine) and no history of parathyroidectomy or renal transplantation. These subjects had mean (SD) age of 65.4 (10.9) years, serum 25D at baseline of 19.6 (5.4) ng/mL, body weight of 97.8 (24.3) kg and BMI of 34.7 (7.9) kg/m2. Fifty percent were male, 64. 0% White, 32.9% African-American or Black, and 3.1% Other, and 20% were Hispanic. A total of 356 subjects completed a 20- to 26-week treatment period per-protocol and were included in the analysis. Enrolled subjects ingested a 30 mcg capsule of ERC (OPKO Pharmaceuticals, Miami) daily for 12 weeks followed by one or two capsules (30 or 60 mcg) daily for a 14 more weeks. Control subjects received matching placebo. Mean (SD) serum 25D remained unchanged with placebo treatment but rose progressively with ERC treatment to 67.1 (21.6) ng/mL (mean of weeks 20-26). The observed increases in serum 25D were inversely related to body weight but exceeded 50 ng/mL in all body weight categories, irrespective of race (White vs. African-American or black), gender or age (<70 vs. ≥70 years). Side effects observed at these levels were similar to placebo. These data showed that ERC successfully raised mean serum 25D to at least 50 ng/mL irrespective of body weight, race, gender or age. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.