糖尿病肾脏疾病患者的光镜下肾小管病变与临床指标关系及对预后的影响

    Associations between renal tubular lesions and clinical parameters as well as prognosis in diabetic kidney disease

    • 摘要: 目的 探讨糖尿病肾脏疾病(diabetic kidney disease,DKD)患者的光镜下肾小管病变与临床指标关系及对预后的影响,为预测DKD患者不良进展提供临床病理依据。方法 纳入2018年1月至2021年4月在新乡医学院第一附属医院经肾活检明确诊断为DKD的患者126例,随访至2021年9月结束,以肾功能不良进展(肾脏替代疗法或血肌酐加倍)作为结局指标。根据肾脏病理光镜下肾小管病变程度分为3组,轻度肾小管病变(light tubulopathy,LT)组41例,中度肾小管病变(moderate tubulopathy,MT)组40例,重度肾小管病变(severe tubulopathy,ST)组45例。结果 相比MT和ST组,LT组的血肌酐、血尿素氮、胱抑素C(cystatin C,Cys C)、总胆固醇、低密度脂蛋白、α1微球蛋白(α1-microglobulin,α1-MG)、β2 微球蛋白(β2-microglobulin,β2-MG)、视黄醇结合蛋白(retinol binding protein,RBP)、尿白蛋白/肌酐比值、超敏C-反应蛋白(high sensitivity C-reactive protein,hs-CRP)、中性粒细胞/淋巴细胞比值(neutrophil/lymphocyte ratio,NLR)、单核细胞/淋巴细胞比值(monocytes/lymphocyteratio,MLR)、肾小球硬化比例、病理分级及临床分期程度偏低,估算肾小球滤过率(estimated glomerularfiltration rate,eGFR)、血钙、血白蛋白水平偏高(P<0.05)。Spearman相关分析显示,肾小管病变与NLR(r=0.205,P=0.021)、MLR(r=0.196,P=0.028)、hs-CRP(r=0.203,P=0.023)、α1-MG(r=0.280,P=0.001)、β2-MG(r=0.348,P<0.001)、RBP(r=0.495,P<0.001)、血肌酐(r=0.627,P<0.001)、血尿素氮(r=0.587,P<0.001)、Cys C(r=0.727,P<0.001)、肾小球硬化比例(r=0.416,P<0.001)、病理分级(r=0.628,P<0.001)、临床分期(r=0.578,P<0.001)均呈正相关。单因素Cox回归分析显示MT、ST、血肌酐、血尿素氮、Cys C、NLR、血小板/淋巴细胞比值(platelet/lymphocyte ratio,PLR)是肾功能不良进展的危险因素,血白蛋白、血钙、eGFR是其保护因素。多因素Cox回归分析显示在模型1、模型2和模型3中MT、ST是肾功能不良进展的独立危险因素。K-M生存曲线显示肾小管病变程度与肾功能不良进展发生存在显著相关(P<0.001)。ROC曲线显示NLR、MLR、PLR、α1-MG、β2-MG、RBP、CysC、血肌酐、血尿素氮在判定肾功能不良进展曲线下面积(AUC)分别为0.638、0.635、0.553、0.678、0.732、0.770、0.853、0.804、0.793,灵敏度为38.8%、42.5%、81.3%、67.5%、81.3%、72.5%、77.5%、72.5%、62.5%,特异度为85.0%、82.5%、32.5%、65.0%、67.5%、75.0%、85.0%、80.0%、87.5%,截断值分别为3.60、0.22、105.37、39.34 mg/L、0.69mg/L、2.74mg/L、1.42mg/L、77.90μmol/L、7.80mmol/L。结论 肾小管病变是肾功能不良进展的独立危险因素。NLR、MLR、α1-MG、β2-MG、RBP、Cys C、血肌酐、血尿素氮在预测肾功能不良进展方面有一定的临床价值。

       

      Abstract: Objective To explore the associations between renal tubular lesions under light microscope and clinical parameters in diabetic kidney disease(DKD)and provide clinicopathological evidence for adverse progression of DKD patients. Methods From January 2018 to April 2021, a total of 126 DKD patients diagnosed by renal biopsy were recruited. Follow-ups ended in September 2021. Progression of renal dysfunction(renal replacement therapy or doubling of serum creatinine)was employed as an outcome parameter. According to microscopic degree of renal tubular lesions, there were light tubulopathy(LT, n=41), moderate tubulopathy(MT, n=40)and severe tubulopathy(ST, n=45). Results Compared with MT and ST groups, serum creatinine, blood urea nitrogen, cystatin C(Cys C), total cholesterol, low-density lipoprotein, α1-microglobulin(α1-MG), β2-microglobulin(β2-MG), retinol binding protein(RBP), urinary albumin/creatinine ratio, high sensitivity C-reactive protein(hs-CRP), neutrophil/lymphocyte ratio(NLR), monocyte/lymphocyte ratio(MLR), glomerulosclerosis ratio, pathological classification and clinical stage were lower in LT group. And eGFR, blood calcium and blood albumin was higher in LT group(P<0.05). Spearman's correlation analysis revealed that renal tubular lesions with NLR(r=0.205, P=0.021), MLR(r=0.196, P=0.028), hs-CRP(r=0.203, P=0.023) with α1-MG (r=0.280, P=0.001), β2-MG (r=0.348, P<0.001), RBP (r=0.495, P<0.001), with serum creatinine(r=0.627, P<0.001), blood urea nitrogen(BUN)(r=0.587, P<0.001), Cys C(r=0.727, P<0.001), glomerulosclerotic ratio(r=0.416, P<0.001), pathological classification(r=0.628, P<0.001)and clinical stage(r=0.578, P<0.001)were positively correlated. Univariate Cox regression analysis showed MT, ST, serum creatinine, blood urea nitrogen, Cys C, NLR and platelet/lymphocyte ratio(PLR)were the risk factors of adverse progression. Serum albumin, blood calcium and estimated glomerular filtration rate(eGFR)were the protective factors. Multivariate Cox regression analysis indicated that both MT and ST were independent risk factors for progression of renal dysfunction in models 1, 2 and 3. Kaplan-Meier survival curve showed that degree of renal tubular lesions was significantly correlated with progression of renal dysfunction(P<0.001). ROC curve indicated that AUCs of NLR, MLR, PLR, α1-MG, β2-MG, RBP, Cys C, serum creatinine and BUN for renal dysfunction were 0.638, 0.635, 0.553, 0.678, 0.732, 0.770, 0.853, 0.804, 0.793, sensitivities 38.8%, 42.5%, 81.3%, 67.5%, 81.3%, 72.5%, 77.5%, 72.5% and 62.5%;specificities 85.0%, 82.5%, 32.5%, 65.0%, 67.5%, 75.0%, 85.0%, 80.0% and 87.5%;cut-off values 3.60, 0.22, 105.37, 39.34 mg/L, 0.69 mg/L, 2.74 mg/L, 1.42 mg/L, 77.90 umol/L and 7.80 mmol/L. Conclusion Tubulopathy is an independent risk factor for progression of renal dysfunction.NLR, MLR, α1-MG, β2-MG, RBP, Cys C, serum creatinine and BUN have certain clinical values in predicting progression of renal dysfunction.

       

    /

    返回文章
    返回