Supplementary Material for: Vitamin D status and treatment in ESKD; links to improved CKD-MBD laboratory parameters in a real-world setting

Introduction: Vitamin D insufficiency is common in patients who receive hemodialysis yet there is no clear guidance regarding surveillance or treatment. We hypothesized that increasing 25(OH)D3 levels is associated with lower phosphate, parathyroid hormone (PTH) and alkaline phosphatase (ALP).

Methods: Baseline 25(OH)D3 level was measured in all patients receiving in-centre hemodialysis in June, 2017. Laboratory parameters were measured every 6 (phosphate, calcium) or 12 weeks (25(OH)D3, PTH, ALP) until February, 2021. In September, 2018 a treatment algorithm of 50,000 IU weekly until sufficient, followed by 50,000 IU monthly was suggested. Generalized linear mixed regression models including linear spline effects, a log link function, and random effects were used to examine the impact of increasing 25(OH)D3 levels on calcium, phosphate, ALP and PTH.

Results: Of 697 participants, 15% and 57% had vitamin D deficiency (25(OH)D3 < 25 nmol/L) and insufficiency (between 25 and 74 nmol/L). Incorporating up to 7272 observations, increasing 25(OH)D3 was associated with significantly decreasing PTH for 25(OH)D3 levels between 25 and 75 nmol/L regardless of vitamin D treatment. In an interaction model, the negative slope between 25(OH)D3 and PTH remained significant beyond 75 nmol/L in the absence of calcitriol. Increasing 25(OH)D3 was associated with significantly decreasing phosphate for 25(OH)D3 levels between 25 and 75nmol/L regardless of vitamin D treatment, and below 25 nmol/L in values of untreated patients. Calcium increased across the spectrum of 25(OH)D3 regardless of vitamin D treatment. 0.2% of 25(OH)D3 levels exceeded 250 nmol/L and 2.1% of calcium levels exceeded the normal range.

Conclusions: Vitamin D treatment in a real-world setting was safe and associated with lower PTH levels. Whether improved biochemical markers translate to a reduction in

## 引言：
维生素D不足在血液透析患者中十分常见，但目前尚无针对其监测与治疗的明确指南。本研究假设，升高的25羟维生素D3（25(OH)D3）水平与更低的血磷、甲状旁腺激素（parathyroid hormone, PTH）及碱性磷酸酶（alkaline phosphatase, ALP）水平相关。

## 方法：
2017年6月，对所有接受中心血液透析的患者检测其基线25羟维生素D3水平。实验室指标每6周检测血磷、血钙，每12周检测25羟维生素D3、甲状旁腺激素、碱性磷酸酶，直至2021年2月。2018年9月，研究者提出一套治疗方案：每周给予50000国际单位（IU），直至维生素D水平达标，后续改为每月50000 IU。本研究采用纳入线性样条效应、对数连接函数与随机效应的广义线性混合回归模型，分析25羟维生素D3水平升高对血钙、血磷、碱性磷酸酶及甲状旁腺激素的影响。

## 结果：
共纳入697名受试者，其中15%存在维生素D缺乏（25(OH)D3 <25 nmol/L），57%存在维生素D不足（25~74 nmol/L）。本研究共纳入7272项观测数据，在25~75 nmol/L的25羟维生素D3浓度范围内，无论是否接受维生素D治疗，25羟维生素D3水平升高均与甲状旁腺激素水平显著降低相关。在交互作用模型中，未使用骨化三醇（calcitriol）的受试者中，25羟维生素D3与甲状旁腺激素之间的负相关斜率在25(OH)D3浓度超过75 nmol/L时仍具有统计学显著性。在25~75 nmol/L的25羟维生素D3浓度范围内，无论是否接受维生素D治疗，25羟维生素D3水平升高均与血磷水平显著降低相关；未接受治疗的患者在25(OH)D3浓度低于25 nmol/L时也呈现这一关联。无论是否接受维生素D治疗，血钙水平均随25羟维生素D3浓度升高而升高。有0.2%的受试者25羟维生素D3浓度超过250 nmol/L，2.1%的受试者血钙水平超出正常参考范围。

## 结论：
真实世界场景下的维生素D治疗安全性良好，且与甲状旁腺激素水平降低相关。改善的生化指标是否能转化为