Brunelli Steven M, Joffe Marshall M, Israni Rubeen K, Yang Wei, Fishbane Steven, Berns Jeffrey S, Feldman Harold I
Renal, Electrolyte and Hypertension Division of the Department of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Clin J Am Soc Nephrol. 2008 May;3(3):777-82. doi: 10.2215/CJN.04281007. Epub 2008 Mar 12.
Hemoglobin variability is common among dialysis patients, and has been associated with increased mortality. The causal nature of this association has been difficult to ascertain because of potential time-dependent confounding, for which traditional statistical methods do not control.
DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: A retrospective cohort of 34,963 Fresenius Medical care dialysis patients from 1996 was assembled. Hemoglobin variability, absolute hemoglobin level, and temporal hemoglobin trend were measured over rolling 6-mo exposure windows. Their association with mortality was estimated using history-adjusted marginal structural analysis that adjusts for time-dependent confounding by applying weights to observations inversely related to the predictability of observed levels of hemoglobin.
In the primary analysis, each g/dl increase in hemoglobin variability was associated with an adjusted hazard ratio (HR) [95% confidence interval (CI)] for all-cause mortality of 1.93 (1.20 to 3.10). Neither higher absolute hemoglobin level nor increasing hemoglobin trend were significantly associated with mortality; adjusted HR (95% CI) 0.85 (0.64 to 1.11) and 0.60 (0.25 to 1.45), respectively.
Marginal structural analysis demonstrates that hemoglobin variability is associated with increased mortality among chronic hemodialysis patients, and that this effect is more pronounced than appreciated using standard statistical techniques that do not take time-dependent confounding into account.
血红蛋白变异性在透析患者中很常见，且与死亡率增加有关。由于存在潜在的时间依赖性混杂因素，这种关联的因果性质难以确定，而传统统计方法无法控制此类因素。
设计、地点、参与者及测量方法：收集了1996年以来34963例费森尤斯医疗护理透析患者的回顾性队列。在滚动的6个月暴露窗口期间测量血红蛋白变异性、绝对血红蛋白水平和血红蛋白时间趋势。使用历史调整的边际结构分析估计它们与死亡率的关联，该分析通过对与观察到的血红蛋白水平可预测性呈负相关的观察值应用权重来调整时间依赖性混杂因素。
在初步分析中，血红蛋白变异性每增加1g/dl，全因死亡率的调整后风险比（HR）[95%置信区间（CI）]为1.93（1.20至3.10）。较高的绝对血红蛋白水平和上升的血红蛋白趋势均与死亡率无显著关联；调整后HR（95%CI）分别为0.85（0.64至1.11）和0.60（0.25至1.45）。
边际结构分析表明，血红蛋白变异性与慢性血液透析患者死亡率增加有关，且这种影响比未考虑时间依赖性混杂因素的标准统计技术所显示的更为明显。
