Am J Epidemiol. 2020 May 5;189(5):433-444. doi: 10.1093/aje/kwz246.
Persons with chronic kidney disease (CKD) are at high risk of infection. While low-grade inflammation could impair immune response, it is unknown whether inflammatory markers are associated with infection risk in this clinical population. Using 2003-2013 data from the Chronic Renal Insufficiency Cohort Study (3,597 participants with CKD), we assessed the association of baseline plasma levels of 4 inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 receptor antagonist (IL-1RA), and transforming growth factor-β (TGF-β)) with incident hospitalization with major infection (pneumonia, urinary tract infection, cellulitis and osteomyelitis, and bacteremia and sepsis). During follow-up (median 7.5 years), 36% (n = 1,290) had incident hospitalization with major infection. In multivariable Cox analyses with each inflammatory marker modeled as a restricted cubic spline, higher levels of IL-6 and TNF-α were monotonically associated with increased risk of hospitalization with major infection (for 95th vs. 5th percentile, hazard ratio = 2.11 (95% confidence interval: 1.68, 2.66) for IL-6 and 1.88 (95% confidence interval: 1.51, 2.33) for TNF-α), while corresponding associations for IL-1RA or TGF-β were nonsignificant. Thus, higher plasma levels of IL-6 and TNF-α, but not IL-1RA or TGF-β, were significantly associated with increased risk of hospitalization with major infection. Future studies should investigate whether inflammatory pathways that involve IL-6 and TNF-α increase susceptibility to infection among individuals with CKD.
患有慢性肾病(CKD)的人感染的风险很高。虽然低水平的炎症可能会损害免疫反应,但目前尚不清楚在这种临床人群中,炎症标志物是否与感染风险相关。本研究利用 2003-2013 年慢性肾功能不全队列研究(3597 例 CKD 患者)的数据,评估了基线血浆中 4 种炎症标志物(白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1 受体拮抗剂(IL-1RA)和转化生长因子-β(TGF-β))水平与主要感染(肺炎、尿路感染、蜂窝织炎和骨髓炎、菌血症和败血症)住院事件的相关性。在随访期间(中位 7.5 年),36%(n=1290)发生了主要感染住院事件。在对每个炎症标志物采用限制立方样条模型的多变量 Cox 分析中,IL-6 和 TNF-α 水平越高,主要感染住院风险越高(第 95 个百分位数与第 5 个百分位数相比,IL-6 的危险比为 2.11(95%置信区间:1.68,2.66),TNF-α 的危险比为 1.88(95%置信区间:1.51,2.33)),而 IL-1RA 或 TGF-β 的对应相关性则无统计学意义。因此,较高的 IL-6 和 TNF-α 血浆水平与主要感染住院风险增加显著相关,而 IL-1RA 或 TGF-β 则没有。未来的研究应探讨涉及 IL-6 和 TNF-α 的炎症途径是否会增加 CKD 患者对感染的易感性。