Karaboyas Angelo, Morgenstern Hal, Fleischer Nancy L, Vanholder Raymond C, Dhalwani Nafeesa N, Schaeffner Elke, Schaubel Douglas E, Akizawa Tadao, James Glen, Sinsakul Marvin V, Pisoni Ronald L, Robinson Bruce M
Arbor Research Collaborative for Health, Ann Arbor, MI.
Department of Epidemiology, University of Michigan, Ann Arbor, MI.
Kidney Med. 2020 Mar 26;2(3):286-296. doi: 10.1016/j.xkme.2020.01.007. eCollection 2020 May-Jun.
RATIONALE & OBJECTIVE: Previous studies of inflammation and anemia management in hemodialysis (HD) patients may be biased due to patient differences. We used a self-matched longitudinal design to test whether new inflammation, defined as an acute increase in C-reactive protein (CRP) level, reduces hemoglobin response to erythropoiesis-stimulating agent (ESA) treatment.
Self-matched longitudinal design.
SETTING & PARTICIPANTS: 3,568 new inflammation events, defined as CRP level > 10 mg/L following a 3-month period with CRP level ≤ 5 mg/L, were identified from 12,389 HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 6 (2009-2018) in 10 countries in which CRP is routinely measured.
"After" (vs "before") observing a high CRP level.
Within-patient changes in hemoglobin level, ESA dose, and ESA hyporesponsiveness (hemoglobin < 10 g/dL and ESA dose > 6,000 [Japan] or >8,000 [Europe] U/wk).
Linear mixed models and modified Poisson regression.
Comparing before with after periods, mean hemoglobin level decreased from 11.2 to 10.9 g/dL (adjusted mean change, -0.26 g/dL), while mean ESA dose increased from 6,320 to 6,960 U/wk (adjusted relative change, 8.4%). The prevalence of ESA hyporesponsiveness increased from 7.6% to 12.3%. Both the unadjusted and adjusted prevalence ratios of ESA hyporesponsiveness were 1.68 (95% CI, 1.48-1.91). These associations were consistent in sensitivity analyses varying CRP thresholds and were stronger when the CRP level increase was sustained over the 3-month after period.
Residual confounding by unmeasured time-varying risk factors for ESA hyporesponsiveness.
In the 3 months after HD patients experienced an increase in CRP levels, hemoglobin levels declined quickly, ESA doses increased, and the prevalence of ESA hyporesponsiveness increased appreciably. Routine CRP measurement could identify inflammation as a cause of worsened anemia. In turn, these findings speak to a potentially important role for anemia therapies that are less susceptible to the effects of inflammation.
既往关于血液透析（HD）患者炎症与贫血管理的研究可能因患者差异而存在偏差。我们采用自身匹配纵向设计，以检验新出现的炎症（定义为C反应蛋白（CRP）水平急性升高）是否会降低血红蛋白对促红细胞生成素（ESA）治疗的反应。
自身匹配纵向设计。
在10个常规检测CRP的国家进行的透析预后与实践模式研究（DOPPS）第4至6阶段（2009 - 2018年）中，从12389例HD患者中识别出3568例新出现的炎症事件，定义为在3个月内CRP水平≤5mg/L后，CRP水平>10mg/L。
观察到高CRP水平后（与之前相比）。
患者体内血红蛋白水平、ESA剂量以及ESA低反应性（血红蛋白<10g/dL且ESA剂量>6000[日本]或>8000[欧洲]U/周）的变化。
线性混合模型和修正泊松回归。
比较前后两个时期，平均血红蛋白水平从ll.2g/dL降至l0.9g/dL（调整后平均变化为 - 0.26g/dL），而平均ESA剂量从6320U/周增至6960U/周（调整后相对变化为8.4%）。ESA低反应性的患病率从7.6%升至12.3%。ESA低反应性的未调整患病率比和调整患病率比均为1.68（95%CI，1.48 - 1.91）。在改变CRP阈值的敏感性分析中，这些关联是一致的，并且当CRP水平在3个月的后期持续升高时更强。
存在未测量的ESA低反应性时变风险因素导致的残余混杂。
在HD患者CRP水平升高后的3个月内，血红蛋白水平迅速下降，ESA剂量增加，且ESA低反应性的患病率显著增加。常规检测CRP可将炎症识别为贫血恶化的一个原因。反过来，这些发现表明对于不太易受炎症影响的贫血治疗可能具有潜在的重要作用。
