中性粒细胞/淋巴细胞比值和血小板/淋巴细胞比值与2型糖尿病患者肾小管损伤的相关性研究

目的探讨中性粒细胞/淋巴细胞(NLR)和血小板/淋巴细胞(PLR)与2型糖尿病(T2DM)患者肾小管损伤的相关性。方法收集2018年9月至2019年9月于中南大学湘雅三医院住院治疗的268例T2DM患者,根据尿白蛋白/肌酐比值(UACR),将其分为正常白蛋白尿组(UACR<30 mg/g)、微量白蛋白尿组(30 mg/g≤UACR<300 mg/g)和大量白蛋白尿组(UACR≥300 mg/g)。收集纳入患者的一般临床资料。空腹抽取肘静脉血检测血常规以及糖化血红蛋白、超敏C反应蛋白(hs-CRP)等生化指标,计算NLR、PLR和预估肾小球滤过率(eGFR),并检测尿α1微球蛋白(α1-MG)、β2-微球蛋白(β2-MG)、视黄醇结合蛋白(RBP)、尿肌酐(Ucr),以α1-MG/Ucr、β2-MG/Ucr和RBP/Ucr作为反映肾小管损伤的指标。采用χ2检验、方差分析及非参数检验对各组指标的差异进行比较,采用Spearman相关分析法分析各炎性指标与肾损伤标志物的相关性,采用受试者工作特征(ROC)曲线分析模型预测价值。结果大量白蛋白尿组(94例)的NLR和PLR明显高于正常白蛋白尿组(94例)和微量白蛋白尿组(80例),微量白蛋白尿组NLR高于正常白蛋白尿组,差异有统计学意义(均P<0.05)。随着NLR、PLR四分位数的递增,患者UACR及RBP/Ucr、α1-MG/Ucr、β2-MG/Ucr逐渐升高,差异具有统计学意义(均P<0.05)。Spearman相关分析显示,NLR、PLR与UACR、RBP/Ucr、α1-MG/Ucr、β2-MG/Ucr均呈正相关(r=0.254~0.385,均P<0.01),与eGFR呈负相关(r=-0.328、-0.151,均P<0.01)。ROC曲线显示,NLR判定UACR>30 mg/g、eGFR<60 ml·min^-1·(1.73 m²)^-1及肾小管损伤的曲线下面积(AUC)分别为0.700、0.679、0.717、0.702、0.737,灵敏度分别为75.29%、85.87%、80.88%、83.74%、85.59%,均优于PLR(AUC分别为0.639、0.639、0.659、0.644、0.676,灵敏度分别为58.05%、75.00%、63.24%、65.04%、58.56%)和hs-CRP(AUC分别为0.597、0.559、0.618、0.644、0.653,灵敏度分别为62.50%、30.12%、63.93%、68.42%、70.87%)。结论NLR和PLR与T2DM患者肾小管损伤密切相关,NLR在综合反映肾小球及肾小管损伤方面优于PLR和hs-CRP。

Association between neutrophil-to-lymphocyte or platelet-to-lymphocyte and renal tubular injury in type 2 diabetes mellitus patients

Objective To explore the association between neutrophil-to-lymphocyte(NLR)or platelet-to-lymphocyte(PLR)and renal tubular injury in type 2 diabetes mellitus(T2DM)patients.Methods A total of 268 patients with T2DM who were hospitalized in the Third Xiangya Hospital of Central South University from September 2018 to September 2019 were assigned to three groups according to their urine albumin/urine creatinine ratio(UACR):normal-albuminuria group(Normal group,UACR<30 mg/g),micro-albuminuria group(Micro group,30≤UACR<300 mg/g),and macro-albuminuria group(Macro group,UACR≥300 mg/g).Basic information and clinical data of the research objects were collected.Fasting extraction of elbow venous blood to test blood routine,and biochemical indicators such as glycated hemoglobin A1c and hypersensitive C-reactive protein(hs-CRP).NLR,PLR and estimated glomerular filtration rate(eGFR)was calculated.After detecting the levels ofα1-microglobulin(α1-MG),β2-microglobulin(β2-MG),retinol-binding protein(RBP)and urinary creatinine(Ucr),we regardedα1-MG/Ucr,β2-MG/Ucr and RBP/Ucr as indicators for responding renal tubular injury.Group differences were tested with Chi-square test,analysis of variance and nonparametric tests.Associations between inflammatory index and renal injury markers were performed by Spearman correlation coefficients.Receiver operator characteristic(ROC)analyses determined the prediction efficiency of model.Results NLR and PLR levels were increased in the Macral group(94 cases)than both the Micro group(80 cases)and the Normal group(94 cases),and the difference was statistically significant(P<0.01).Compared with the Micro group,NLR levels in the Macro group were increased in Macro group(P<0.05).With the increase in NLR and PLR quartiles,there were gradual increase in UACR,urine RBP/Ucr,urineα1-MG and urineβ2-MG,and the differences were statistically significant(P<0.05).Spearman correlation analysis showed that NLR and PLR had positive correletions with UACR,RBP/Ucr,α1-MG/Ucr andβ2-MG/Ucr(r=0.254-0.385,all P<0.01),and a negative correlation with eGFR(r=-0.328,-0.151,both P<0.01).In addition,ROC curve analyses showed that the AUC and sensitivities of NLR in predicting UACR>30 mg/g,eGFR<60 ml·min^-1·(1.73 m²)^-1,RBP/Ucr>0.10,α1-MG/Ucr>2.08,orβ2-MG/Ucr>0.07(AUC were 0.700,0.679,0.717,0.702,0.737,respectively;sensitivities were 75.29%,85.87%,80.88%,83.74%,85.59%,respectively)were all higher than those of PLR(AUC were 0.639,0.639,0.659,0.644,0.676,respectively;sensitivities were 58.05%,75.00%,63.24%,65.04%,58.56%,respectively)and hs-CRP(AUC were 0.597,0.559,0.618,0.644,0.653,respectively;sensitivities were 62.50%,30.12%,63.93%,68.42%,70.87%,respectively).Conclusion Both NLR and PLR are closely related to renal tubular injury in patients with T2DM,and NLR is superior to PLR or hs-CRP not only in reflecting glomerular damage but also in tubular injury.