C反应蛋白/白蛋白比值是腹膜透析患者死亡的独立影响因素

C⁃reactive protein to albumin ratio is an independent influencing factor of mortality in peritoneal dialysis patients

目的探讨C反应蛋白(C-reactive protein,CRP)/白蛋白(albumin,ALB)比值(CRP to ALB ratio,CAR)与腹膜透析(peritoneal dialysis,PD)患者死亡的相关性。方法回顾性收集2004年1月1日至2019年12月31日苏州大学附属第二医院PD中心791例PD患者的临床资料,按照入选患者基线CAR三分位数分为3组:低CAR组(CAR≤0.161 mg/g,n=264)、中CAR组(CAR 0.162~0.214 mg/g,n=263)、高CAR组(CAR≥0.215 mg/g,n=264),比较3组临床资料的差异。随访截至2020年3月31日,终点事件为死亡、转为血液透析、肾移植、肾功能恢复终止PD。采用Kaplan-Meier法、多因素Cox回归模型及Fine-Gray竞争风险模型分析CAR水平和PD患者全因死亡和心脑血管疾病死亡的关系。使用受试者工作特征曲线(ROC曲线)比较CAR和其他炎症指标[CRP、ALB和中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)]与PD患者死亡的相关性。结果入选患者年龄为(59.8±15.7)岁,男性447例(56.5%),高血压714例(90.3%),合并糖尿病233例(29.5%),合并心血管疾病182例(23.0%)。中位随访时间为55(31,88)个月,至随访终点236例(29.8%)患者死亡,其中心脑血管疾病死亡95例(12.0%)。Kaplan-Meier生存分析结果显示,高CAR组患者的总体生存率明显低于低CAR组和中CAR组(Log-rank检验χ^(2)=109.50,P<0.001)。多因素Cox回归分析结果显示,校正混杂因素后,CAR与PD患者全因死亡风险独立相关(HR=2.891,95%CI 1.921~4.351,P<0.001)。Fine-Gray竞争风险模型分析结果显示,校正混杂因素后,CAR与心脑血管疾病死亡风险相关(SHR=1.297,95%CI 1.128~1.490,P<0.001)。ROC曲线分析结果显示,CAR预测PD患者全因死亡风险的ROC曲线下面积(AUC)为0.737(95%CI 0.700~0.774),显著高于CRP(AUC=0.643,95%CI 0.599~0.687)、NLR(AUC=0.608,95%CI 0.563~0.653)和PLR(AUC=0.554,95%CI 0.508~0.601)等炎症指标,略低于ALB(AUC=0.752,95%CI 0.716~0.788),其最佳截断值为0.19 mg/g,敏感度和特异度分别为70.8%和68.3%。结论CAR水平升高是PD患者全因死亡和心脑血管疾病死亡的独立危险因素,其与PD患者死亡的相关性高于CRP、NLR及PLR等传统炎症指标。

Objective To investigate the association between C⁃reactive protein(CRP)/albumin(ALB)ratio(CAR)and mortality in peritoneal dialysis(PD)patients.Methods Clinical data of 791 PD patients in the Second Affiliated Hospital of Soochow University from January 1,2004 to December 31,2019 were retrospectively collected.According to the baseline quartiles of CAR,patients were divided into three groups:low⁃level CAR group(CAR≤0.161 mg/g,n=264),medium⁃level CAR group(CAR 0.162-0.214 mg/g,n=263)and high⁃level CAR group(CAR≥0.215 mg/g,n=264).The clinical data among the three groups were compared.Follow⁃up was ended on March 31,2020,or when the patients stopped PD due to death,shift to hemodialysis,renal transplantation or recovery of renal function.Kaplan⁃Meier survival curve,multivariate Cox proportional hazard model and Fine⁃Gray competing risk model were used to assess the relationship between CAR and all⁃cause mortality and cardiovascular and cerebrovascular mortality.The association between CAR,CRP,ALB,neutrophil to lymphocyte ratio(NLR),or platelet to lymphocyte ratio(PLR)and mortality in PD patients was compared by receiver⁃operating characteristic curve(ROC curve)analysis.Results The age of the patients was(59.8±15.7)years old,and 447(56.5%)patients were males.714(90.3%)patients had hypertension.233(29.5%)patients had diabetes.182(23.0%)patients had cardiovascular diseases.The median follow⁃up time was 55(31,88)months.By the end of the follow⁃up,236 deaths(29.8%)happened,and 95 patients(12.0%)died from cardiovascular and cerebrovascular diseases.Kaplan⁃Meier survival analysis results showed that the overall survival rate of the high⁃level CAR group was lower than those of the low⁃level CAR group and medium⁃level CAR group(Log⁃rank testχ^(2)=109.50,P<0.001).Multivariate Cox regression analysis and Fine⁃Gray competing risk model revealed that CAR was independently correlated with all⁃cause mortality and cardiovascular and cerebrovascular mortality after adjusting for confounding factors(HR=2.891,95%CI 1.921-4.351,P<0.001;SHR=1.297,95%CI 1.128-1.490,P<0.001).ROC curve analysis results showed that the area under the curve(AUC)of CAR for predicting the risk of all⁃cause mortality in PD patients was 0.737(95%CI 0.700-0.774),which was superior to those of CRP(AUC=0.643,95%CI 0.599-0.687),NLR(AUC=0.608,95%CI 0.563-0.653)and PLR(AUC=0.554,95%CI 0.508-0.601),and slightly lower than ALB(AUC=0.752,95%CI 0.716-0.788).The optimal cutoff value of CAR for death was 0.19 mg/g,with the sensitivity and specificity of 70.8%and 68.3%,respectively.Conclusions Increasing CAR level is an independent risk factor of all⁃cause mortality and cardiovascular and cerebrovascular mortality in PD patients,and its correlation with mortality is higher than those of inflammatory parameters such as CRP,NLR and PLR.