Supplementary Material for: Pre-End-Stage Renal Disease Hemoglobin Variability Predicts Post-End-Stage Renal Disease Mortality in Patients Transitioning to Dialysis

<b><i>Background:</i></b> Hemoglobin variability (Hb-var) has been associated with increased mortality both in non-dialysis dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD) patients. However, the impact of Hb-var in advanced NDD-CKD on outcomes after dialysis initiation remains unknown. <b><i>Methods:</i></b> Among 11,872 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 through September 2011, we assessed Hb-var calculated from the residual SD of at least 3 Hb values during the last 6 months before dialysis initiation (prelude period) using within-subject linear regression models, and stratified into quartiles. Outcomes included post-transition all-cause, cardiovascular, and infection-related mortality, assessed in Cox proportional hazards models and adjusted for demographics, comorbidities, length of hospitalization, medications, estimated glomerular filtration rate (eGFR), type of vascular access, Hb parameters (baseline Hb [i.e., intercept] and change in Hb [i.e., slope]), and number of Hb measurements. <b><i>Results:</i></b> Higher prelude Hb-var was associated with use of iron and antiplatelet agents, tunneled dialysis catheter use, higher levels of baseline Hb, change in Hb, eGFR, and serum ferritin. After multivariable adjustment, higher prelude Hb-var was associated with higher post-ESRD all-cause and infection-related mortality, but not cardiovascular mortality (adjusted hazard ratios [95% CI] for the highest [vs. lowest] quartile of Hb-var, 1.10 [1.02–1.19], 1.28 [0.93–1.75], and 0.93 [0.79–1.10], respectively). <b><i>Conclusions:</i></b> High pre-ESRD Hb-var is associated with higher mortality, particularly from infectious causes rather than cardiovascular causes. Further research is required to clarify the underlying mechanisms and true causal nature of the observed association.

**背景**：血红蛋白变异性（Hemoglobin variability, Hb-var）与非透析依赖性慢性肾脏病（non-dialysis dependent chronic kidney disease, NDD-CKD）及终末期肾病（end-stage renal disease, ESRD）患者的死亡率升高均存在关联。然而，晚期非透析依赖性慢性肾脏病患者的Hb-var对透析启动后临床结局的影响仍未明确。
**方法**：本研究纳入2007年10月至2011年9月期间转为维持性透析的11872名美国退伍军人晚期NDD-CKD患者。采用受试者内线性回归模型，计算透析启动前6个月（即预备期）内至少3次血红蛋白检测值的残差标准差以评估Hb-var，并将患者按Hb-var水平分为四等分位组。研究结局包括转为透析后的全因死亡、心血管死亡及感染相关死亡，采用Cox比例风险模型（Cox proportional hazards models）进行分析，并对人口学特征、合并症、住院时长、用药情况、估算肾小球滤过率（estimated glomerular filtration rate, eGFR）、血管通路类型、血红蛋白参数（基线血红蛋白[即截距项]及血红蛋白变化[即斜率]）以及血红蛋白检测次数进行校正。
**结果**：较高的预备期Hb-var与铁剂及抗血小板药物使用、隧道式透析导管置入、更高的基线血红蛋白水平、血红蛋白变化量、eGFR及血清铁蛋白水平相关。经多变量校正后，较高的预备期Hb-var与ESRD术后全因死亡及感染相关死亡风险升高相关，但与心血管死亡无显著关联（Hb-var最高四分位组相较于最低四分位组的校正后风险比[95%置信区间]依次为1.10[1.02–1.19]、1.28[0.93–1.75]及0.93[0.79–1.10]）。
**结论**：ESRD前较高的Hb-var与更高的死亡率相关，尤其是感染相关死亡而非心血管死亡。仍需开展进一步研究以阐明该关联的潜在机制及真正的因果关系。