Renal Transplant Associates of New England, Springfield, MA, USA.
Shoals Kidney and Hypertension Center, Florence, AL, USA.
BMC Nephrol. 2022 Nov 11;23(1):362. doi: 10.1186/s12882-022-02993-3.
Extended-release calcifediol (ERC), active vitamin D hormones and analogs (AVD) and nutritional vitamin D (NVD) are commonly used therapies for treating secondary hyperparathyroidism (SHPT) in adults with stage 3-4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). Their effectiveness for increasing serum total 25-hydroxyvitamin D (25D) and reducing elevated plasma parathyroid hormone (PTH), the latter of which is associated with increased morbidity and mortality, has varied across controlled clinical trials. This study aimed to assess real-world experience of ERC and other vitamin D therapies in reducing PTH and increasing 25D.
Medical records of 376 adult patients with stage 3-4 CKD and a history of SHPT and VDI from 15 United States (US) nephrology clinics were reviewed for up to 1 year pre- and post-ERC, NVD or AVD initiation. Key study variables included patient demographics, concomitant usage of medications and laboratory data. The mean age of the study population was 69.5 years, with gender and racial distributions representative of the US CKD population. Enrolled patients were grouped by treatment into three cohorts: ERC (n = 174), AVD (n = 55) and NVD (n = 147), and mean baseline levels were similar for serum 25D (18.8-23.5 ng/mL), calcium (Ca: 9.1-9.3 mg/dL), phosphorus (P: 3.7-3.8 mg/dL) and estimated glomerular filtration rate (eGFR: 30.3-35.7 mL/min/1.73m). Mean baseline PTH was 181.4 pg/mL for the ERC cohort versus 156.9 for the AVD cohort and 134.8 pg/mL (p < 0.001) for the NVD cohort. Mean follow-up during treatment ranged from 20.0 to 28.8 weeks.
Serum 25D rose in all cohorts (p < 0.001) during treatment. ERC yielded the highest increase (p < 0.001) of 23.7 ± 1.6 ng/mL versus 9.7 ± 1.5 and 5.5 ± 1.3 ng/mL for NVD and AVD, respectively. PTH declined with ERC treatment by 34.1 ± 6.6 pg/mL (p < 0.001) but remained unchanged in the other two cohorts. Serum Ca increased 0.2 ± 0.1 pg/mL (p < 0.001) with AVD but remained otherwise stable. Serum alkaline phosphatase remained unchanged.
Real-world clinical effectiveness and safety varied across the therapies under investigation, but only ERC effectively raised mean 25D (to well above 30 ng/mL) and reduced mean PTH levels without causing hypercalcemia.
在患有 3-4 期慢性肾脏病（CKD）和维生素 D 不足（VDI）的成年人中，通常使用活性维生素 D 激素及其类似物（AVD）和营养性维生素 D（NVD）作为治疗继发性甲状旁腺功能亢进症（SHPT）的药物。在控制良好的临床试验中，这些药物在增加血清总 25-羟维生素 D（25D）和降低升高的血浆甲状旁腺激素（PTH）方面的有效性各不相同，后者与发病率和死亡率的增加有关。本研究旨在评估 ERC 和其他维生素 D 疗法在降低 PTH 和增加 25D 方面的真实世界经验。
回顾了来自美国 15 家肾病诊所的 376 名患有 3-4 期 CKD 且有 SHPT 和 VDI 病史的成年患者的医疗记录，这些患者在 ERC、NVD 或 AVD 治疗开始前和开始后最长达 1 年的时间内进行了评估。主要研究变量包括患者的人口统计学数据、同时使用的药物和实验室数据。研究人群的平均年龄为 69.5 岁，性别和种族分布与美国 CKD 人群一致。根据治疗方法将患者分为三组：ERC 组（n=174）、AVD 组（n=55）和 NVD 组（n=147），基线时血清 25D（18.8-23.5ng/mL）、钙（Ca：9.1-9.3mg/dL）、磷（P：3.7-3.8mg/dL）和估算肾小球滤过率（eGFR：30.3-35.7mL/min/1.73m）水平相似。ERC 组的基线 PTH 平均为 181.4pg/mL，AVD 组为 156.9pg/mL，NVD 组为 134.8pg/mL（p<0.001）。治疗期间的平均随访时间为 20.0-28.8 周。
所有组的血清 25D 在治疗期间均升高（p<0.001）。与 NVD 和 AVD 组分别升高 9.7±1.5ng/mL 和 5.5±1.3ng/mL 相比，ERC 组升高幅度最大（p<0.001），升高了 23.7±1.6ng/mL。在 ERC 治疗下，PTH 下降了 34.1±6.6pg/mL（p<0.001），而其他两组则没有变化。血清 Ca 增加了 0.2±0.1pg/mL（p<0.001），而 AVD 则保持不变。血清碱性磷酸酶保持不变。
在研究的治疗方法中，真实世界的临床疗效和安全性各不相同，但只有 ERC 能有效提高血清 25D（升高至 30ng/mL 以上）和降低 PTH 水平，而不会导致高钙血症。
