Supplementary Material for: The Association of Low Hemoglobin Levels with IgA Nephropathy Progression: A Two-Center Cohort Study of 1,828 Cases

Aim: To investigate the relationship between hemoglobin levels and the progression of IgA nephropathy (IgAN). Methods: In a two-center cohort of 1,828 cases with biopsy-proven IgAN, we examined the association of hemoglobin levels with the primary outcome of a composite of all-cause mortality or kidney failure defined as a 40% decline in eGFR, or ESKD (defined as eGFR <15 mL/min/1.73 m2 or need for kidney replacement therapy including hemodialysis, peritoneal dialysis, or kidney transplantation), or the outcome of kidney failure, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. Results: At baseline, mean age, eGFR, and hemoglobin levels were 33.75 ± 11.03 years, 99.70 ± 30.40 mL/min/1.73 m2, and 123.47 ± 18.36 g/L, respectively. During a median of approximately 7-year follow-up, 183 cases reached the composite outcome. After adjustment for demographic and IgAN-specific covariates and treatments, a lower quartile of hemoglobin was nonlinearly associated with an increased risk of the primary outcome or kidney failure in the Cox proportional hazards models (primary outcome: HR for quartile 3 vs. 4, 1.37; 95% CI, 0.83–2.25; HR for quartile 2 vs. 4, 1.18; 95% CI, 0.68–2.07; HR for quartile 1 vs. 4, 1.91; 95% CI, 1.15–3.17; kidney failure: HR for quartile 3 vs. 4, 1.39; 95% CI, 0.84–2.31; HR for quartile 2 vs. 4, 1.20; 95% CI, 0.68–2.11; HR for quartile 1 vs. 4, 1.83; 95% CI, 1.09–3.07) in the fully adjusted model. Then, hemoglobin levels were transformed to a binary variable for fitting the model according to the criteria for anemia of 110 g/L in the women and 120 g/L in men in China. The participants in the anemia group had an increased risk of developing outcomes compared with the nonanemia group in both genders (primary outcome: male: HR, 1.64; 95% CI, 1.01–2.68; female: HR, 1.68; 95% CI, 1.02–2.76; kidney failure: male: HR, 1.60; 95% CI, 0.97–2.64; female: HR, 1.58; 95% CI, 0.95–2.61) in the fully adjusted model. Conclusions: A low level of hemoglobin was nonlinearly associated with IgAN progression. The anemic IgAN patients presented a higher risk of developing poor outcomes compared with the nonanemic patients.研究目的：探讨血红蛋白（hemoglobin）水平与IgA肾病（IgA nephropathy, IgAN）病情进展的关联。 研究方法：本研究纳入双中心队列中经肾活检确诊的1828例IgAN患者，以全因死亡或肾功能衰竭作为主要复合终点，其中肾功能衰竭定义为估算肾小球滤过率（estimated glomerular filtration rate, eGFR）下降40%，或终末期肾病（end-stage kidney disease, ESKD，即eGFR<15 mL/min/1.73 m²或需接受肾脏替代治疗，包括血液透析、腹膜透析或肾移植）；分别采用Cox比例风险回归（Cox proportional hazards regression）与logistic回归（logistic regression）模型分析血红蛋白水平与上述终点的关联，并对混杂因素进行校正。 研究结果：基线时，研究对象的平均年龄为33.75±11.03岁，平均eGFR为99.70±30.40 mL/min/1.73 m²，平均血红蛋白水平为123.47±18.36 g/L。在中位随访约7年期间，共183例患者达到主要复合终点。经人口学特征、IgAN特异性协变量及治疗方案校正后，完全校正模型的Cox比例风险回归分析结果显示，血红蛋白四分位水平与主要终点或肾功能衰竭风险呈非线性关联：以四分位4组为参照，四分位3组的主要终点风险比（hazard ratio, HR）为1.37，95%置信区间（confidence interval, CI）为0.83~2.25；四分位2组HR为1.18，95%CI为0.68~2.07；四分位1组HR为1.91，95%CI为1.15~3.17；肾功能衰竭方面，四分位3组HR为1.39，95%CI为0.84~2.31；四分位2组HR为1.20，95%CI为0.68~2.11；四分位1组HR为1.83，95%CI为1.09~3.07。随后，依据中国成人贫血诊断标准（女性血红蛋白≤110 g/L、男性≤120 g/L）将血红蛋白水平转换为二分类变量进行模型拟合。完全校正模型结果显示，无论男女，贫血组患者发生不良结局的风险均高于非贫血组：主要终点方面，男性HR=1.64，95%CI=1.01~2.68；女性HR=1.68，95%CI=1.02~2.76；肾功能衰竭方面，男性HR=1.60，95%CI=0.97~2.64；女性HR=1.58，95%CI=0.95~2.61。 研究结论：低血红蛋白水平与IgAN病情进展呈非线性关联。贫血IgAN患者发生不良结局的风险显著高于非贫血患者。