Supplementary Material for: Race, Mineral Homeostasis and Mortality in Patients with End-Stage Renal Disease on Dialysis

<b><i>Background:</i></b> Abnormalities in mineral homeostasis are ubiquitous in patients on dialysis, and influenced by race. In this study, we determine the race-specific relationship between mineral parameters and mortality in patients initiating hemodialysis. <b><i>Methods:</i></b> We measured the levels of fibroblast growth factor 23 (FGF23) and 25-hydroxyvitamin D (25 D) in 184 African American and 327 non-African American hemodialysis patients who enrolled between 1995 and 1998 in the Choices for Healthy Outcomes in Caring for ESRD Study. Serum calcium, phosphorus, parathyroid hormone (PTH) and total alkaline phosphatase levels were averaged from clinical measurements during the first 4.5 months of dialysis. We evaluated the associated prospective risk of mortality using multivariable Cox proportional hazards models stratified by race. <b><i>Results:</i></b> PTH and total alkaline phosphatase levels were higher, whereas calcium, phosphorus, FGF23 and 25 D levels were lower in African Americans compared to those of non-African Americans. Higher serum phosphorus and FGF23 levels were associated with greater mortality risk overall; however, phosphorus was only associated with risk among African Americans (HR 5.38, 95% CI 2.14-13.55 for quartile 4 vs. 1), but not among non-African Americans (p-interaction = 0.04). FGF23 was associated with mortality in both groups, but more strongly in African Americans (HR 3.91, 95% CI 1.74-8.82 for quartiles 4 vs. 1; p-interaction = 0.09). Serum calcium, PTH, and 25 D levels were not consistently associated with mortality. The lowest and highest quartiles of total alkaline phosphatase were associated with higher mortality risk, but this did not differ by race (p-interaction = 0.97). <b><i>Conclusions:</i></b> Aberrant phosphorus homeostasis, reflected by higher phosphorus and FGF23, may be a risk factor for mortality in patients initiating hemodialysis, particularly among African Americans.

**背景：** 矿物质稳态（mineral homeostasis）异常在透析患者中普遍存在，且受种族因素影响。本研究旨在明确初始血液透析患者中，矿物质代谢指标与死亡率之间的种族特异性关联。
**方法：** 本研究纳入1995年至1998年间参与「终末期肾病护理健康结局选择研究（Choices for Healthy Outcomes in Caring for ESRD Study）」的184名非裔美国人及327名非非裔美国人血液透析患者，检测其成纤维细胞生长因子23（fibroblast growth factor 23, FGF23）与25-羟维生素D（25-hydroxyvitamin D, 25(OH)D）水平。采集患者透析开始后前4.5个月内的临床检测结果，计算血清钙、磷、甲状旁腺激素（parathyroid hormone, PTH）及总碱性磷酸酶的平均水平。采用按种族分层的多变量Cox比例风险回归模型（multivariable Cox proportional hazards models），评估死亡率的前瞻性关联风险。
**结果：** 与非非裔美国人相比，非裔美国人的PTH及总碱性磷酸酶水平更高，而血清钙、磷、FGF23及25(OH)D水平更低。总体而言，血清磷及FGF23水平升高与死亡率风险升高相关；但磷水平仅在非裔美国人中与死亡率风险相关（第4四分位数组vs第1四分位数组的风险比（hazard ratio, HR）为5.38，95%置信区间（confidence interval, CI）为2.14~13.55），而非非裔美国人中无此关联（交互作用P=0.04）。两组中FGF23水平均与死亡率相关，但非裔美国人中的关联更强（第4四分位数组vs第1四分位数组的HR为3.91，95%CI为1.74~8.82；交互作用P=0.09）。血清钙、PTH及25(OH)D水平与死亡率未呈现一致的关联。总碱性磷酸酶最低及最高四分位数组均与死亡率风险升高相关，但该关联不存在种族差异（交互作用P=0.97）。
**结论：** 以血清磷及FGF23水平升高反映的磷稳态异常，可能是初始血液透析患者的死亡率风险因素，尤其在非裔美国人中更为显著。