Bae Eunjin, Cha Ran-Hui, Kim Yong C, An Jung N, Kim Dong K, Yoo Kyung D, Lee Su M, Kim Myoung-Hee, Park Jung T, Kang Shin-Wook, Park Jae Y, Lim Chun S, Kim Yon S, Yang Seung H, Lee Jung P
Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon Department of Internal Medicine, National Medical Center Department of Internal Medicine, Seoul National University College of Medicine Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul Department of Internal Medicine, Dongguk University Medical Center, Gyeongju Department of Internal Medicine, Dong-A University, Busan Department of Dental Hygiene, College of Health Science, Eulji University, Seongnam Department of Internal Medicine, Yonsei University College of Medicine, Seoul Department of Internal Medicine, Dongguk University Medical Center, Goyang Kidney Research Institute, Seoul National University, Seoul, Republic of Korea.
Medicine (Baltimore). 2017 May;96(19):e6666. doi: 10.1097/MD.0000000000006666.
Cardiovascular disease (CVD) is the main public health problem in patients with chronic kidney disease (CKD); however, there is no established biomarker for predicting CVD morbidity and mortality in CKD. The aim of this study was to evaluate the role of circulating tumor necrosis factor receptors (cTNFRs) in predicting CVD risk in CKD patients.We prospectively recruited 984 patients with CKD from 11 centers between 2006 and 2012. The levels of cTNFR1 and cTNFR2 were determined by performing an enzyme-linked immunosorbent assay. During the mean follow-up period of 4 years, 36 patients experienced a CVD event. The median serum concentrations of cTNFR1 and cTNFR2 were 2703.4 (225.6-13,057.7) and 5661.0 (634.9-30,599.6) pg/mL, respectively, and the cTNFR1 level was closely correlated with the cTNFR2 level (r = 0.86, P < .0001). The urinary protein-to-creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) were significantly correlated with the cTNFR2 level (r = 0.21 for UPCR, r = -0.67 for eGFR; P < .001 for all). Similar correlations were observed for serum cTNFR1 (r = 0.21 for UPCR, r = -0.75 for eGFR; P < .001 for all). In the Cox proportional hazard analyses, cTNFR1 (hazard ratio [HR] 2.506, 95% confidence interval [CI] 1.186-5.295, P = .016) and cTNFR2 (HR 4.156, 95% CI 1.913-9.030, P < .001) predicted CVD risk even after adjustment for clinical covariates, such as UPCR, eGFR, and high-sensitivity C-reactive protein. cTNFR1 and 2 are associated with CVD and other risk factors in CKD, independently of eGFR and UPCR. Furthermore, cTNFRs could be relevant predictors of CVD in CKD patients.
心血管疾病（CVD）是慢性肾脏病（CKD）患者的主要公共卫生问题；然而，目前尚无用于预测CKD患者CVD发病率和死亡率的确立生物标志物。本研究的目的是评估循环肿瘤坏死因子受体（cTNFRs）在预测CKD患者CVD风险中的作用。我们在2006年至2012年间从11个中心前瞻性招募了984例CKD患者。通过酶联免疫吸附测定法测定cTNFR1和cTNFR2的水平。在平均4年的随访期内，36例患者发生了CVD事件。cTNFR1和cTNFR2的血清中位浓度分别为2703.4（225.6 - 13057.7）和5661.0（634.9 - 30599.6）pg/mL，且cTNFR1水平与cTNFR2水平密切相关（r = 0.86，P < .0001）。尿蛋白肌酐比（UPCR）和估算肾小球滤过率（eGFR）与cTNFR2水平显著相关（UPCR的r = 0.21；eGFR的r = -0.67；均P < .001）。血清cTNFR1也观察到类似的相关性（UPCR的r = 0.21；eGFR的r = -0.75；均P < .001）。在Cox比例风险分析中，即使在调整临床协变量（如UPCR、eGFR和高敏C反应蛋白）后，cTNFR1（风险比[HR] 2.506，95%置信区间[CI] 1.186 - 5.295，P = .016）和cTNFR2（HR 4.156，95% CI 1.913 - 9.030，P < .001）仍可预测CVD风险。cTNFR1和2与CKD中的CVD及其他风险因素相关，独立于eGFR和UPCR。此外，cTNFRs可能是CKD患者CVD的相关预测指标。
