Kimachi Miho, Fukuma Shingo, Yamazaki Shin, Yamamoto Yosuke, Akizawa Tadao, Akiba Takashi, Saito Akira, Fukuhara Shunichi
Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan.
Nephron. 2015;131(2):123-30. doi: 10.1159/000438870. Epub 2015 Sep 8.
Hemodialysis (HD) patients occasionally experience minor asymptomatic elevation in C-reactive protein (CRP) levels, which may be associated with difficulty in managing renal anemia using erythropoiesis-stimulating agents (ESAs). Here, we assessed whether elevation of CRP predicts future incidences of ESA hyporesponsiveness.
A total of 2,956 HD patients lacking ESA hyporesponsiveness and infectious diseases were enrolled, and the association between CRP levels and incidence of ESA hyporesponsiveness was assessed. CRP levels were divided into 4 categories (normal [<1.0 mg/l], mild [1.0 ≤ CRP <3.0 mg/l], moderate [3.0 ≤ CRP <10.0 mg/l] and high [≥ 10.0 mg/l]). The primary outcome was the cumulative incidence of ESA hyporesponsiveness, defined as a failure to achieve hemoglobin level ≥ 10 g/dl despite receiving high doses of ESAs (≥ 9,000 U/week recombinant human epoetin [rHuEPO]-α or rHuEPO-β and ≥ 60 μg/week darbepoetin-α) during 12 months of follow-up.
The cumulative incidence of ESA hyporesponsiveness was 134 (4.8%) occurrences over 4 months and 300 (12.4%) over 12 months. The elevated CRP groups had significantly higher incidence of ESA hyporesponsiveness over 4 months of follow-up than the normal reference group (adjusted relative risk [RR] 1.6, 95% CI 1.0-2.6 for moderate; adjusted RR 2.5, 95% CI 1.5-4.1 for high). Furthermore, the association remained consistent even over 12 months (adjusted RR 1.4, 95% CI 1.0-1.8 for moderate; adjusted RR 1.6, 95% CI 1.1-2.4 for high).
Elevated CRP levels were associated with future incidence of ESA hyporesponsiveness from low-grade inflammation (3.0 ≤ CRP <10.0 mg/l).
血液透析（HD）患者偶尔会出现C反应蛋白（CRP）水平轻微无症状升高，这可能与使用促红细胞生成素（ESA）治疗肾性贫血困难有关。在此，我们评估了CRP升高是否可预测未来ESA低反应性的发生率。
共纳入2956例无ESA低反应性和传染病的HD患者，评估CRP水平与ESA低反应性发生率之间的关联。CRP水平分为4类（正常[<1.0mg/l]、轻度[1.0≤CRP<3.0mg/l]、中度[3.0≤CRP<10.0mg/l]和重度[≥10.0mg/l]）。主要结局是ESA低反应性的累积发生率，定义为在12个月随访期间，尽管接受高剂量ESA（≥9000U/周重组人促红细胞生成素[rHuEPO]-α或rHuEPO-β以及≥60μg/周达贝泊汀-α），血红蛋白水平仍未达到≥10g/dl。
ESA低反应性的累积发生率在4个月时为134例（4.8%），12个月时为300例（12.4%）。在4个月的随访中，CRP升高组的ESA低反应性发生率显著高于正常参考组（中度调整相对风险[RR]1.6，95%CI 1.0 - 2.6；重度调整RR 2.5，95%CI 1.5 - 4.1）。此外，即使在12个月时该关联仍保持一致（中度调整RR 1.4，95%CI 1.0 - 1.8；重度调整RR 1.6，95%CI 1.1 - 2.4）。
CRP水平升高与低度炎症（3.0≤CRP<10.0mg/l）导致的未来ESA低反应性发生率相关。
