Supplementary Material for: Mortality and Hospitalizations among Sickle Cell Disease Patients with End-Stage Kidney Disease Initiating Dialysis

<b><i>Background:</i></b> Sickle cell disease (SCD) is the most common inherited hematological disorder and a well-described risk factor for end-stage kidney disease (ESKD). Mortality and hospitalizations among patients with SCD who develop ESKD remain understudied. Furthermore, prior studies focused only on SCD patients where ESKD was caused by SCD. We aimed to describe mortality and hospitalization risk in all SCD patients initiating dialysis and explore risk factors for mortality and hospitalization. <b><i>Methods:</i></b> We performed a national observational cohort study of African American ESKD patients initiating dialysis (2000–2014) in facilities affiliated with a large dialysis provider. SCD was identified by diagnosis codes and matched to a reference population (non-SCD) by age, sex, dialysis initiation year, and geographic region of care. Sensitivity analyses were conducted by restricting to patients where SCD was recorded as the cause of ESKD. <b><i>Results:</i></b> We identified 504 SCD patients (mean age: 47 ± 14 years; 48% females) and 1,425 reference patients (mean age: 46 ± 14 years; 49% females). The median follow-up was 2.4 (IQR 1.0–4.5) years. Compared to the reference, SCD was associated with higher mortality risk (hazard ratio 1.66; 95% confidence interval [CI]: 1.36–2.03) and higher hospitalization rates (incidence rate ratio 2.12; 95% CI: 1.88–2.38) in multivariable analyses. Exploratory multivariable mortality risk models showed the largest mortality risk attenuation with the addition of time-varying hemoglobin and high-dose erythropoietin, but the association of SCD with mortality remained significant. Sensitivity analyses (restricted to ESKD caused by SCD) also showed significant associations between SCD and mortality and hospitalizations, but with larger effect estimates. High-dose erythropoietin was associated with the highest risk for mortality and hospitalization in SCD. <b><i>Conclusions:</i></b> Among ESKD patients, SCD is associated with a higher risk for mortality and hospitalization, particularly in patients where SCD is identified as the cause of ESKD.

**背景**：镰状细胞病（Sickle cell disease, SCD）是最常见的遗传性血液系统疾病，同时也是终末期肾病（end-stage kidney disease, ESKD）明确的高危致病因素。目前针对并发ESKD的SCD患者的死亡率与住院率相关研究仍较为匮乏。此外，既往研究仅聚焦于ESKD由SCD直接引发的SCD患者群体。本研究旨在全面描述所有启动透析治疗的SCD患者的死亡与住院风险，并探索其死亡与住院的危险因素。
**方法**：本研究针对2000至2014年间，在大型透析服务机构旗下医疗机构启动透析治疗的非洲裔美国ESKD患者开展一项全国性观察性队列研究。通过诊断编码识别SCD患者，并按照年龄、性别、透析启动年份以及诊疗地域与非SCD的对照人群进行匹配。本研究同时开展敏感性分析，将分析范围限定于以SCD作为ESKD致病原因的患者群体。
**结果**：本研究共纳入504例SCD患者（平均年龄47±14岁，女性占比48%）与1425例对照患者（平均年龄46±14岁，女性占比49%）。中位随访时长为2.4年（四分位间距interquartile range, IQR：1.0~4.5年）。多变量分析结果显示，相较于对照人群，SCD与更高的死亡风险相关（风险比hazard ratio：1.66；95%置信区间confidence interval, CI：1.36~2.03），同时住院率也显著升高（发病率比incidence rate ratio：2.12；95%CI：1.88~2.38）。探索性多变量死亡风险模型分析显示，加入时变血红蛋白与大剂量促红细胞生成素两个变量后，组间死亡风险差异出现最大程度的衰减，但SCD与死亡风险的相关性仍具有统计学意义。敏感性分析（限定于SCD所致ESKD患者）同样显示SCD与死亡及住院风险存在显著关联，且效应量更大。在SCD患者中，大剂量促红细胞生成素与最高的死亡及住院风险相关。
**结论**：在ESKD患者群体中，SCD与更高的死亡及住院风险显著相关，尤其在以SCD作为ESKD致病原因的患者中更为显著。