目的 研究外周血双特异性磷酸酶6(dual-specificity phosphatase 6，Dusp6)联合临床参数对维持性腹膜透析患者全因死亡及心血管事件死亡的预测价值。 方法 选择行腹膜透析置管并开始进行持续性腹膜透析的患者进行前瞻性队列研究，检测外周血Dusp6水平并收集基线临床资料，随访全因死亡和心血管事件死亡。采用Kaplan-Meier法比较不同Dusp6水平患者的死亡率，采用COX回归模型分析全因死亡和心血管事件死亡的影响因素，采用ROC曲线分析全因死亡和心血管事件死亡的预测指标。 结果 共纳入138例患者，随访时间19(15，23)月；外周血Dusp6水平的中位数为38.9 pg/ml，外周血Dusp6≥38.9 pg/ml患者的全因死亡率和心血管事件死亡率均高于Dusp6＜38.9 pg/ml(χ2=17.500， P＜0.001，χ2=10.560,P=0.001)；年龄、低密度脂蛋白胆固醇、C反应蛋白、Dusp6水平是患者全因死亡的影响因素(HR =1.104、3.105、21.929、1.075，95% CI：1.021～1.193、1.069～9.013、6.280～76.575、1.008～1.147，P=0.013、0.037、＜0.001、0.028)，4项指标联合预测全因死亡的灵敏度为81.11%、特异度为80.17%；年龄、尿酸、C反应蛋白、Dusp6水平是患者心血管事件死亡的影响因素(HR=1.095、2.985、4.646、1.105，95% CI：1.003～1.195、1.219～8.938、1.597～13.517、1.003～1.184，P=0.042、0.032、0.005、0.004)，4项指标联合预测心血管事件死亡的灵敏度为81.25%、特异度为80.77%。 结论 外周血Dusp6高表达与维持性腹膜透析患者全因死亡及心血管事件死亡有关，Dusp6与不同临床参数联合对全因死亡及心血管事件死亡具有一定预测价值。
Objective To investigate dual-specificity phosphatase 6 (Dusp6) in peripheral blood combined with clinical parameters to predict all-cause death and cardiovascular event death in maintenance peritoneal dialysis (PD) patients. Methods Patients who underwent PD catheterization and maintenance PD were selected for the single-center and prospective cohort study. Dusp6 in peripheral blood was measured. Baseline clinical data, all-cause death and cardiovascular event death were collected. Kaplan-Meier method was used to compare the mortality of PD patients with different levels of Dusp6. Cox regression model was used to analyze the influencing factors for all-cause death and cardiovascular event death. ROC curve was used to evaluate the predictive indicators for all-cause death and cardiovascular event death. Results A total of 138 PD patients were included and followed up for 19 (15, 23) month. There were 48 all-cause death cases (34.78%) and 26 cardiovascular death cases (18.84%). The median level of Dusp6 in peripheral blood was 38.9pg/ml. The all-cause mortality and cardiovascular event mortality in patients with peripheral blood Dusp6 ≥38.9pg/ml were higher than in those with Dusp6 ＜38.9 pg/ml (χ²=17.5, P＜0.001; χ²=10.56, P=0.001). Age, low density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP) and Dusp6 were the influencing factors for all-cause death (HR=1.104, 3.105, 21.929 and 1.075 respectively; 95% CI:1.021～1.193, 1.069～9.013, 6.280～76.575 and 1.008～1.147 respectively; P=0.013, 0.037, ＜0.001 and 0.028 respectively); when combined the 4 influencing factors to predict all-cause death, the sensitivity and specificity were 81.11% and 80.17% respectively. Age, uric acid, CRP and Dusp6 were the influencing factors for cardiovascular event death; when combined the 4 influencing factors to predict cardiovascular event death, the sensitivity and specificity were 81.25% and 80.77% respectively. Conclusion The high expression of Dusp6 in peripheral blood is associated with all-cause death and cardiovascular event death in PD patients. The combination of Dusp6 and other related clinical parameters has better predictive values for all-cause death and cardiovascular event death in PD patients.
[1]Min L, Jin Y, Hao Z, et al. Analysis of outcome and factors correlated with maintenance peritoneal dialysis[J]. Journal of International Medical Research, 2019, 47(10): 4683-4690.
[2]Shymova A, Shifris I, Dudar I, et al. Nutritional status and survival of End-Stage Renal Disease patients treated with continuous ambulatory peritoneal dialysis[J]. Ukrainian Journal of Nephrology and Dialysis, 2019, 2(62): 33-40.
[3]Zhou X, Zhang C, Wu X, Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction[J]. Nature Communications, 2022, 13(1): 6672.
[4]王鸿利, 何琴, 刘帆, 等. miR-145-5p 通过靶向 DUSP6 抑制 LPS 诱导的血管内皮细胞氧化损伤和炎症[J]. 中国免疫学杂志, 2021, 37(20): 2457-2461.
[5]Baldolli A, Daurel C, Verdon R, et al. High mortality in peritonitis due to Mycobacterium avium complex: retrospective study and systematic literature review[J]. Infectious diseases, 2019, 51(2): 81-90.
[6]Fabbian F, De Giorgi A, Ferrara F, et al. Comorbidity and in-hospital mortality in peritoneal dialysis patients: data of the Emilia Romagna region of Italy[J]. European review for medical and pharmacological sciences, 2023, 27(14): 6867-6875.
[7]Banshodani M, Kawanishi H, Moriishi M, et al. Association between Dialysis Modality and Cardiovascular Diseases: A Comparison between Peritoneal Dialysis and Hemodialysis[J]. Blood purification, 2020, 49(3): 302-309.
[8]Li J, Huang N, Zhong Z, et al. Risk factors and outcomes of cardiovascular disease readmission within the first year after dialysis in peritoneal dialysis patients[J]. Renal failure, 2021, 43(1): 159-167.
[9]Dev J, Yeoungjee C, David J, et al. Clinical Studies of Interventions to Mitigate Cardiovascular Risk in Peritoneal Dialysis Patients[J]. Seminars in Nephrology, 2018, 38(3): 277-290.
[10]Gennip A, Broers N, Meulen K, et al. Endothelial dysfunction and low-grade inflammation in the transition to renal replacement therapy[J]. PloS one, 2019, 14(9): e0222547.
[11]Kocyigit H, Koyuncu S, Kocyigit I, et al. The effect of sodium exchange and dialytic biochemical parameters on blood pressure, arterial stiffness, and endothelial functions in patients with peritoneal dialysis[J]. International urology and nephrology, 2020, 52(11): 1-7.
[12]Sacnun J, Hoogenboom R, Eibensteiner F, et al. Proteome-Wide Differential Effects of Peritoneal Dialysis Fluid Properties in an In Vitro Human Endothelial Cell Model[J]. International Journal of Molecular Sciences, 2022, 23(14): 8010.
[13]Zhang Z, Chen Y, Zheng L, et al. A DUSP6 inhibitor suppresses inflammatory cardiac remodeling and improves heart function after myocardial infarction[J]. Dis Model Mech, 2023, 16(5): dmm049662.
[14]Qiu Y, Ye H, Wang Y, et al. Age Difference in the Association between Hyponatremia and Infection-Related Mortality in Peritoneal Dialysis Patients[J]. Blood purification, 2020, 49(5): 631-640.
[15]郐婷婷, 王志宏, 金蕊, 等. 血清基线低密度脂蛋白胆固醇水平对维持性血液透析患者预后影响的回顾性队列研究[J]. 中国实用内科杂志, 2022, 42(6): 495-499.
[16]郭雪梅, 朱朕男, 许杨, 等. 血清尿酸与维持性血液透析患者死亡的相关性[J]. 临床肾脏病杂志, 2023, 23(5): 381-387.
[17]Dao B, Pham N, Nguyen M, et al. High Serum Uric Acid and High-Sensitivity C Reactive Protein Concentrations Predict Three-Year Cardiovascular Mortality in Patients Treated With Continuous Ambulatory Peritoneal Dialysis[J]. 2021, 13(9): e17900.
[18]于源, 张东伟, 李辉, 等. PLR、PTH 及 CRP 与老年维持性血液透析患者全因 及心血管事件死亡的关系[J]. 分子诊断与治疗杂志, 2023, 15(8): 1353-1356, 1361.
