Wändell Per, Feldreich Tobias, Larsson Anders, Kalra Philip A, Ärnlöv Johan, Ruge Toralph, Carlsson Axel C
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
School of Health and Welfare, Dalarna University, Falun, Sweden.
Ups J Med Sci. 2024 Nov 25;129. doi: 10.48101/ujms.v129.10726. eCollection 2024.
Higher circulating levels of tumor necrosis factor (TNF) alpha receptors 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function.
To study associations between levels of TNFR1 and TNFR2 and all-cause mortality as well as estimated glomerular filtration rate (eGFR) decline.
Patients with chronic kidney disease (CKD) stages 3-5 in the Salford Kidney Study were included. Associations between one standard deviation increase in TNFR1 and TNFR2 and mortality were estimated by Cox regression models with hazard ratios (HRs) and 95% confidence intervals adjusted for age, sex, eGFR based on creatinine and cystatin C, urine-protein, C-reactive protin, cardiovascular comorbidity, smoking habits, and diabetes. Differences in eGFR decline in relation to TNFR1 and TNFR2 were estimated by both linear and logistic regression models, with regression coefficients and odds ratios (ORs).
Univariate models showed significant associations between TNFR1 and TNFR2 and all-cause mortality based on 7424 person-years at risk, but in the fully adjusted models with continuous variables significant only for TNFR2 HR 1.17 (1.03-1.34), but with a borderline value for TNFR1 HR 1.15 (1.00-1.31). For rapid decliners, that is, eGFR decline in highest TNFR-receptor quartile versus quartiles 1-3, the decline was 1.60% per month (interval 0.78-10.99). For eGFR decline in continuous models, the fully adjusted ORs were for TNFR1 1.29 (0.92-1.81) and for TNFR2 1.33 (0.90-1.98).
TNFR2 was associated with mortality, but TNFR1 was not, although showing a borderline value. Neither TNFR1 nor TNFR2 predicted decline in kidney function. TNFR1 and TNFR2 portray interesting aspects in patients with CKD, but the clinical utility seems limited.
循环中肿瘤坏死因子（TNF）α受体1（TNFR1）和2（TNFR2）水平升高与长期死亡率增加及肾功能受损有关。
研究TNFR1和TNFR2水平与全因死亡率以及估计肾小球滤过率（eGFR）下降之间的关联。
纳入索尔福德肾脏研究中3 - 5期慢性肾脏病（CKD）患者。通过Cox回归模型估计TNFR1和TNFR2每增加一个标准差与死亡率之间的关联，得出风险比（HRs）和95%置信区间，并对年龄、性别、基于肌酐和胱抑素C的eGFR、尿蛋白、C反应蛋白、心血管合并症、吸烟习惯和糖尿病进行校正。通过线性和逻辑回归模型估计与TNFR1和TNFR2相关的eGFR下降差异，得出回归系数和比值比（ORs）。
单变量模型显示，基于7424人年的风险，TNFR1和TNFR2与全因死亡率之间存在显著关联，但在对连续变量进行完全校正的模型中，仅TNFR2有显著意义，HR为1.17（1.03 - 1.34），而TNFR1的HR为1.15（1.00 - 1.31），处于临界值。对于快速下降者，即eGFR在TNFR受体最高四分位数组与第1 - 3四分位数组相比的下降情况，下降速率为每月1.60%（区间为0.78 - 10.99）。在连续模型中eGFR下降方面，完全校正后的ORs对于TNFR1为1.29（0.92 - 1.81），对于TNFR2为1.33（0.90 - 1.98）。
TNFR2与死亡率相关，但TNFR1虽处于临界值却无此关联。TNFR1和TNFR2均不能预测肾功能下降。TNFR1和TNFR2在CKD患者中呈现出有趣的方面，但临床实用性似乎有限。
