Renal Division, OPKO Health, Inc., Miami, Florida, USA.
Vifor Pharma, Ltd., Zurich, Switzerland.
Am J Nephrol. 2022;53(6):446-454. doi: 10.1159/000524289. Epub 2022 May 12.
Obesity increases the risk of vitamin D insufficiency, which exacerbates secondary hyperparathyroidism in chronic kidney disease. Recent studies suggest that serum total 25-hydroxyvitamin D (25OHD) levels of ≥50 ng/mL are necessary to produce significant reductions in elevated parathyroid hormone levels in nondialysis patients. Data from real-world and randomized controlled trials (RCTs) involving these patients were examined for (1) relationships between vitamin D treatments and the achieved levels of serum 25OHD and between serum 25OHD and body weight (BW)/body mass index (BMI); and (2) the impact of BW/BMI on achieving serum 25OHD levels ≥50 ng/mL with extended-release calcifediol (ERC) treatment or vitamin D supplementation (cholecalciferol or ergocalciferol).
Data obtained from nondialysis patients participating in two real-world studies, one conducted in Europe (Study 1) and the other (Study 2) in the USA, and in two US RCTs (Studies 3 and 4) were analyzed for serum 25OHD outcomes after treatment with ERC, vitamin D supplements, or placebo.
More than 50% of subjects treated with vitamin D supplements in both real-world studies (Studies 1 and 2) failed to achieve serum 25OHD levels ≥30 ng/mL, a level widely viewed by nephrologists as the threshold of adequacy; only 7.3-7.5% of subjects achieved levels ≥50 ng/mL. Data from the European study (Study 1) showed that serum 25OHD levels had significant and nearly identical inverse relationships with BW and BMI, indicating that high BW or BMI thwarts the ability of vitamin D supplements to raise serum 25OHD. One RCT (Study 3) showed that 8 weeks of ERC treatment (60 μg/day) raised serum 25OHD levels to ≥30 and 50 ng/mL in all subjects, regardless of BW, while cholecalciferol (300,000 IU/month) raised serum 25OHD to these thresholds in 56% and 0% of subjects, respectively. The other RCT (Study 4) showed that ERC treatment (30 or 60 μg/day) successfully raised mean serum 25OHD levels to at least 50 ng/mL for subjects in all BW categories, whereas no increases were observed with placebo treatment.
Real-world studies conducted in Europe and USA in nondialysis patients (Studies 1 and 2) showed that vitamin D supplements (cholecalciferol or ergocalciferol) were unreliable in raising serum total 25OHD to targets of 30 or 50 ng/mL. In contrast, ERC was demonstrated to be effective in one real-world study (Study 2) and two RCTs (Studies 3 and 4) conducted in US nondialysis patients in raising serum 25OHD to these targeted levels irrespective of BW.
肥胖会增加维生素 D 不足的风险，而维生素 D 不足会使慢性肾脏病患者的继发性甲状旁腺功能亢进恶化。最近的研究表明，非透析患者的血清总 25-羟维生素 D（25OHD）水平需要达到≥50ng/ml，才能显著降低升高的甲状旁腺激素水平。对涉及这些患者的真实世界研究和随机对照试验（RCT）的数据进行了检查，以评估（1）维生素 D 治疗与血清 25OHD 水平之间的关系，以及血清 25OHD 与体重（BW）/体重指数（BMI）之间的关系；（2）BW/BMI 对使用延长释放型碳酸钙（ERC）治疗或维生素 D 补充（胆钙化醇或麦角钙化醇）使血清 25OHD 水平达到≥50ng/ml 的影响。
对参加两项真实世界研究（研究 1 和研究 2）和两项美国 RCT（研究 3 和研究 4）的非透析患者的数据进行分析，以评估 ERC、维生素 D 补充剂或安慰剂治疗后血清 25OHD 的结果。
在两项真实世界研究（研究 1 和研究 2）中，接受维生素 D 补充剂治疗的患者中，超过 50%的患者未能达到血清 25OHD 水平≥30ng/ml，这一水平被肾病学家广泛认为是充足的阈值；只有 7.3-7.5%的患者达到了≥50ng/ml 的水平。来自欧洲研究（研究 1）的数据表明，血清 25OHD 水平与 BW 和 BMI 呈显著的负相关，这表明 BW 或 BMI 会阻碍维生素 D 补充剂提高血清 25OHD 的能力。一项 RCT（研究 3）表明，8 周的 ERC 治疗（每天 60μg）可使所有患者的血清 25OHD 水平升至≥30 和 50ng/ml，而胆钙化醇（30 万 IU/月）分别使 56%和 0%的患者的血清 25OHD 升至这些阈值。另一项 RCT（研究 4）表明，ERC 治疗（每天 30 或 60μg）可使所有 BW 类别的患者的平均血清 25OHD 水平成功升高至至少 50ng/ml，而安慰剂治疗则没有观察到这种升高。
在欧洲和美国进行的非透析患者的真实世界研究（研究 1 和研究 2）表明，维生素 D 补充剂（胆钙化醇或麦角钙化醇）在将血清总 25OHD 提高到 30 或 50ng/ml 的目标值方面不可靠。相比之下，在一项真实世界研究（研究 2）和两项在美国进行的 RCT（研究 3 和研究 4）中，ERC 被证明在提高血清 25OHD 至这些目标水平方面是有效的，而与 BW 无关。
