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Abstract Disclosure: C.W. Bishop: Employee; Self; OPKO Health Inc. A. Ashfaq: Employee; Self; OPKO Health Inc. S.A. Strugnell: Employee; Self; OPKO Health Inc. J. Choe: Employee; Self; OPKO Health Inc. N. Patel: Employee; Self; OPKO Health Inc. K. Norris: None. S.M. Sprague: Consulting Fee; Self; OPKO Health Inc. Low serum 25-hydroxyvitamin D (25D) increases the risk of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). SHPT advances in most CKD patients because elevated parathyroid hormone (PTH) levels are not promptly and effectively controlled. While SHPT is associated with accelerated CKD progression, the association of effective control of SHPT with mitigation of disease progression has not been previously examined. In an attempt to define an appropriate PTH target, pooled RCT data from non-dialysis (ND) CKD patients treated with extended-release calcifediol (ERC) were evaluated to examine the potential impact on CKD progression of controlling plasma intact PTH (iPTH) to modestly elevated levels (≤100 pg/mL). Estimated glomerular filtration rate (eGFR) was examined post-hoc in 126 patients with vitamin D insufficiency, SHPT and stage 3-4 CKD treated for 1 year with ERC in pivotal trials. ERC was administered daily at 30 μg increasing, as needed, after 12 weeks to 60 µg to achieve a ≥30% reduction in iPTH. The majority of subjects (74%) titrated to 60 µg/day. Measurements of eGFR, serum intact fibroblast growth factor 23 (FGF23), serum bone turnover markers and spot urine albumin-to-creatinine ratio were obtained at baseline (BL) and at quarterly intervals, and serum total 25D total 1,25-dihydroxyvitamin D (1,25D), calcium (corrected for low albumin) and phosphorus, and plasma iPTH at BL and biweekly or monthly intervals. Mean iPTH levels at BL and the four quarterly intervals were considered consistently controlled if ≤100 pg/mL. ERC treatment increased mean serum 25D from 20.5±0.49 (SE) ng/mL at BL to 79.0±2.28 ng/mL after 52 weeks of treatment (EOT; p0.001). Serum 1,25D increased progressively from 34.9±1.18 pg/ml to 45.1±2.14 (p0.001) and iPTH decreased from 143.8±5.79 pg/mL to 108.8±7.16 (p0.001) with rising 25D. The relationship across all subjects between rising 1,25D and decreasing iPTH was linear (R2=0.83) showing that, on average, each 10 pg/mL increase in circulating 1,25D yielded a 37 pg/mL decrease in iPTH, irrespective of eGFR. Mean eGFR was stable during the 52-week treatment period in subjects achieving consistent iPTH control (n=25) but declined by -4.1±0.68 mL/min/1.73m2 (-17.9±2.86%; p0.05) in subjects who never achieved control (n=35), with intermittent declines seen with intermediate durations of control. Duration of iPTH control had no negative effect on safety parameters. Sustained suppression of elevated iPTH with ERC to levels of ≤100 pg/mL was safe and associated with slower rates of eGFR decline in patients with stage 3 or 4 CKD. Presentation: 6/1/2024
Bishop et al. (Tue,) studied this question.