Supplementary Material for: Mean Corpuscular Volume and Mortality in Incident Hemodialysis Patients

<b><i>Background/Aims:</i></b> Anemia is common in patients with advanced chronic kidney disease (CKD). A proportion of patients present with macrocytic anemia, manifested by elevated mean corpuscular volume (MCV), which has been associated with worse outcomes in CKD patients. However, it is unknown whether elevated MCV is associated with higher mortality risk in incident hemodialysis (HD) patients. <b><i>Methods:</i></b> This retrospective observational cohort study examined all-cause, cardiovascular, and infectious mortality associations with both baseline and time-varying MCV in 109,501 incident HD patients using Cox proportional hazards models with 3 levels of hierarchical multivariable adjustment. Odds ratios of high versus low baseline MCV were evaluated using logistic regression. <b><i>Results:</i></b> The mean age of patients was 65 ± 15 (standard deviation) years and the cohort was 44% female, 58% diabetic, and 31% African American. Higher MCV was associated with older age, female sex, non-Hispanic White race-ethnicity, alcohol consumption, and having a decreased albumin or protein intake. Patients with higher MCV levels (&gt; 98 fL) had a higher all-cause, cardiovascular, and infectious mortality risk in both baseline and time varying models, and across all levels of adjustment. In the fully adjusted models, compared to a reference of MCV 92–&lt; 94 fL, patients with a baseline MCV &gt; 100+ fL had a 28% higher risk of all-cause mortality (hazard ratio [HR] 1.28, 95% CI 1.22–1.34), 27% higher risk of cardiovascular mortality (HR 1.27, 95% CI 1.18–1.36), and 18% higher risk of infectious mortality (HR 1.18, 95% CI 1.02–1.38). Associations of higher MCV with these adverse outcomes persisted across all examined subgroups of clinical characteristics. <b><i>Conclusions:</i></b> Higher MCV was associated with higher all-cause, cardiovascular, and infectious mortality in HD patients. Further investigation is necessary to understand the underlying nature of the observed association.

**背景与目的：** 贫血在晚期慢性肾脏病（chronic kidney disease，CKD）患者中十分常见。部分患者会表现为大细胞性贫血，以平均红细胞体积（mean corpuscular volume，MCV）升高为特征，该指标升高与慢性肾脏病患者的不良预后相关。然而，目前尚不清楚在新发血液透析（hemodialysis，HD）患者中，MCV升高是否与更高的死亡风险存在关联。

**研究方法：** 本回顾性观察队列研究纳入109501名新发血液透析患者，采用Cox比例风险模型结合三级分层多变量校正策略，分析基线状态及随时间变化的MCV与全因死亡、心血管死亡及感染性死亡的关联；同时通过logistic回归分析基线MCV高低分组的比值比。

**研究结果：** 本队列患者的平均年龄为65±15岁（标准差），其中女性占比44%，糖尿病患者占比58%，非裔美国人占比31%。MCV水平更高的患者多为高龄人群、女性、非西班牙裔白人种族族裔，存在饮酒习惯，且白蛋白水平降低或蛋白质摄入不足。MCV＞98fL的患者，无论在基线分析模型还是随时间变化的分析模型中，且在所有校正层级下，均呈现出更高的全因死亡、心血管死亡及感染性死亡风险。在完全校正模型中，以MCV 92~<94fL作为参照组，基线MCV＞100fL的患者全因死亡风险升高28%（风险比[hazard ratio，HR] 1.28，95%置信区间[confidence interval，CI] 1.22~1.34），心血管死亡风险升高27%（HR 1.27，95%CI 1.18~1.36），感染性死亡风险升高18%（HR 1.18，95%CI 1.02~1.38）。在所有检测的临床特征亚组中，MCV升高与上述不良结局的关联均持续存在。

**研究结论：** 血液透析患者的MCV升高与更高的全因死亡、心血管死亡及感染性死亡风险相关。未来需开展进一步研究以阐明该关联的潜在机制。