血管生成素-2 可预测男性而非女性终末期肾病血液透析患者的全因死亡率。
Angiopoietin-2 predicts all-cause mortality in male but not female end-stage kidney disease patients on hemodialysis.
机构信息
Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
出版信息
Nephrol Dial Transplant. 2022 Jun 23;37(7):1348-1356. doi: 10.1093/ndt/gfab332.
BACKGROUND
Angiopoietin-2 (Ang-2) plays a pivotal role in pathological vascular remodeling and angiogenesis. Both vascular mechanisms are active in patients with end-stage renal disease (ESRD) and may contribute to the high mortality in these patients. The aim of this multicenter prospective cohort study was to investigate baseline serum Ang-2 concentrations in ESRD patients on hemodialysis (HD) for their ability to predict all-cause mortality.
METHODS
We conducted a prospective cohort study in 340 stable HD patients from different chronic dialysis centers in Berlin, Germany. The primary endpoint was all-cause mortality during a 5-year follow-up period. Blood samples and clinical data were collected at baseline. Serum Ang-2 was measured with a validated enzyme-linked immunosorbent assay (Biomedica, Vienna, Austria).
RESULTS
A total of 313 HD patients (206 men and 107 women) were finally included in the study. Receiver operating characteristic (ROC) analysis of Ang-2 concentrations yielded an area under the curve (AUC) of 0.65 (P < 0.0001) for predicting all-cause mortality in the entire study population and was used to determine the optimal cut-off (111.0 pmol/L) for all-cause mortality. Kaplan-Meier survival analysis indicated that male but not female end-stage kidney disease patients on HD with higher Ang-2 concentrations had a significantly lower survival (log-rank test, P < 0.0001 and P = 0.380 for male and female patients, respectively). Multivariable Cox regression analyses adjusted for age, comorbidity, smoking, dialysis vintage, serum creatinine, hemoglobin, C-reactive protein, serum albumin, intact parathyroid hormone (iPTH), low-density lipoprotein (LDL) and Kt/V likewise indicated that elevated Ang-2 concentrations are associated with all-cause mortality in male {hazard ratio [HR] 3.294 [95% confidence interval (CI) 1.768-6.138]; P = 0.0002} but not in female end-stage kidney disease patients on HD [HR 1.084 (95% CI 0.476-2.467); P = 0.847].
CONCLUSION
Ang-2 at baseline is independently associated with all-cause mortality in male ESRD patients on HD.
背景
血管生成素 2（Ang-2）在病理性血管重塑和血管生成中起着关键作用。这两种血管机制在终末期肾病（ESRD）患者中均活跃，并可能导致这些患者死亡率升高。本多中心前瞻性队列研究的目的是研究血液透析（HD）的 ESRD 患者的基线血清 Ang-2 浓度，以评估其预测全因死亡率的能力。
方法
我们在德国柏林的不同慢性透析中心进行了一项 340 例稳定 HD 患者的前瞻性队列研究。主要终点是 5 年随访期间的全因死亡率。在基线时采集血样和临床数据。使用经过验证的酶联免疫吸附测定法（Biomedica，维也纳，奥地利）测量血清 Ang-2。
结果
共有 313 例 HD 患者（206 名男性和 107 名女性）最终纳入研究。Ang-2 浓度的受试者工作特征（ROC）分析为整个研究人群的全因死亡率预测提供了 0.65 的曲线下面积（AUC）（P<0.0001），并用于确定全因死亡率的最佳截断值（111.0 pmol/L）。Kaplan-Meier 生存分析表明，男性而非女性 HD 患者中 Ang-2 浓度较高的终末期肾病患者的生存率显著降低（对数秩检验，P<0.0001 和 P=0.380，分别为男性和女性患者）。调整年龄、合并症、吸烟、透析年限、血清肌酐、血红蛋白、C 反应蛋白、血清白蛋白、完整甲状旁腺激素（iPTH）、低密度脂蛋白（LDL）和 Kt/V 后多变量 Cox 回归分析同样表明，升高的 Ang-2 浓度与男性全因死亡率相关{风险比[HR]3.294（95%置信区间[CI]1.768-6.138）；P=0.0002}，但与女性 HD 患者的全因死亡率无关[HR 1.084（95% CI 0.476-2.467）；P=0.847]。
结论
基线时的 Ang-2 与男性 HD 患者的全因死亡率独立相关。
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