Xiang Fangfang, Zhang Zhen, Nie Yuxin, Cao Xuesen, Li Yang, Chen Xiaohong, Gong Shaomin, Zou Jianzhou, Teng Jie, Ding Xiaoqiang, Shen Bo
Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Shanghai Key Laboratory of Renal Disease and Blood Purification, Shanghai, People's Republic of China.
J Inflamm Res. 2025 Jan 27;18:1267-1279. doi: 10.2147/JIR.S498575. eCollection 2025.
Infection is the most common cause of hospitalization and the second most common cause of mortality among patients undergoing hemodialysis (HD). The enzyme CD73, a cell surface 5'-nucleotidase, regulates the balance between pro-inflammatory nucleotides and anti-inflammatory adenosine. Diminished CD73-adenosine signaling contributes to severe infections.
In this prospective cohort study, 393 patients who underwent HD for over six months were evaluated for CD73Tcell ratios and were followed up for three years to track infection events. Kaplan-Meier curves and Cox regression analyses were used to evaluate the relationship between CD73T cells and infections; meanwhile, multiple logistic regression analysis was used to analyze differences among infection groups. In addition, a 5/6 nephrectomy (5/6 Nx) rat model and cecal ligation and puncture (CLP) were used to verify the effect of chronic kidney disease (CKD) and sepsis on CD73-adenosine signaling.
Decreased CD73 T cells were independently associated with increased infection risk over one and three years. The hazard ratios for one- and three-year infection incidences were 3.173 (95% CI 1.782-5.650, p < 0.001) and 1.429 (95% CI 1.052-1.992, p = 0.035), respectively. Furthermore, they were associated with recurrent and fatal severe infections. Animal models demonstrated reduced CD73 mRNA transcript and adenosine receptor levels, along with decreased serum adenosine levels in CKD. Impairment of CD73-adenosine signaling was more pronounced after CLP in CKD rats.
Lower CD73T cell levels are strongly associated with infection complications in patients undergoing HD. Altered CD73-adenosine signaling likely plays a substantial role in immune dysfunction in CKD.
感染是住院治疗最常见的原因，也是接受血液透析（HD）患者死亡的第二大常见原因。酶CD73是一种细胞表面5'-核苷酸酶，可调节促炎核苷酸和抗炎腺苷之间的平衡。CD73-腺苷信号减弱会导致严重感染。
在这项前瞻性队列研究中，对393例接受HD治疗超过六个月的患者进行了CD73 T细胞比例评估，并随访三年以追踪感染事件。采用Kaplan-Meier曲线和Cox回归分析来评估CD73 T细胞与感染之间的关系；同时，采用多元逻辑回归分析来分析感染组之间的差异。此外，使用5/6肾切除术（5/6 Nx）大鼠模型和盲肠结扎穿刺术（CLP）来验证慢性肾脏病（CKD）和脓毒症对CD73-腺苷信号的影响。
CD73 T细胞减少与一年和三年期间感染风险增加独立相关。一年和三年感染发生率的风险比分别为3.173（95%CI 1.782 - 5.650，p < 0.001）和1.429（95%CI 1.052 - 1.992，p = 0.035）。此外，它们与复发性和致命性严重感染相关。动物模型显示CKD中CD73 mRNA转录本和腺苷受体水平降低，同时血清腺苷水平下降。CKD大鼠在CLP后CD73-腺苷信号的损伤更为明显。
HD患者中较低的CD73 T细胞水平与感染并发症密切相关。CD73-腺苷信号改变可能在CKD的免疫功能障碍中起重要作用。
