血清miR-155和Smad5水平对急性肾衰竭血液透析患者的预后价值评估

    Prognostic value of serum levels of miR-155 and Smad5 in hemodialysis patients with acute renal failure

      摘要
    • 摘要:
      目的  分析血清miR-155和Smad5水平对急性肾衰竭血液透析患者的预后评估价值。
      方法  本研究选取2018年8月至2019年7月恩施土家族苗族自治州中心医院收治的接受血液透析的急性肾衰竭患者120例作为研究组，另选取健康体检者116名作为对照组,根据3年的电话随访记录患者是否存活分为存活组和死亡组；采用定量反转录PCR（quantitative reverse transcriptase-mediated PCR，qRT-PCR）法检测血清miR-155和Smad5 mRNA的表达水平；采用Pearson法分析血清miR-155和Smad5 mRNA表达水平的相关性以及二者与肌酐和尿素氮的相关性；采用 Kaplan-Meier对急性肾衰竭血液透析患者的生存情况进行分析。用Cox回归分析影响急性肾衰竭血液透析患者预后的因素；受试者工作特征曲线（receiver operating characteristic curve, ROC）分析血清miR-155和Smad5 mRNA水平对急性肾衰竭血液透析患者预后的预测价值。
      结果  研究组血清miR-155（2.65±0.71）比（1.01±0.24）、肌酐（289.32±35.64）µmoL/L比（87.65±10.32）µmoL/L和尿素氮(14.78±3.69)mmoL/L比(5.69±1.23)mmoL/L水平显著高于对照组（P＜0.05），Smad5 mRNA(0.78±0.21)比(1.02±0.23)水平显著低于对照组（P＜0.05）。根据Pearson相关性分析，血清miR-155和Smad5 mRNA水平呈负相关（r = −0.538，P＜0.05），血清miR-155表达水平与肌酐、尿素氮水平呈正相关（r = 0.489、0.532，P均＜0.05），血清Smad5 mRNA表达水平与肌酐、尿素氮水平呈负相关（r = −0.475、−0.558，P均＜0.05）。存活组血清miR-155(2.38±0.59)和(3.22±0.90)和肌酐(223.21±29.35)µmoL/L和(426.62±48.32)µmoL/L和尿素氮(11.95±3.15)mmoL/L和(20.67±4.78)mmoL/L的水平显著低于死亡组（P＜0.05），Smad5 mRNA(0.84±0.23)和(0.67±0.18)的表达水平显著高于死亡组（P＜0.05）。根据Kaplan-Meier生存曲线分析表明，miR-155高表达组生存率显著低于低表达组（χ2 = 4.219，P = 0.040），Smad5 mRNA高表达组生存率显著高于低表达组（χ2 = 7.590，P = 0.006）。根据Cox回归分析得知，miR-155、Smad5 mRNA、肌酐和尿素氮是影响急性肾衰竭血液透析患者预后的危险因素（P＜0.05）。血清miR-155预测急性肾衰竭血液透析患者预后的曲线下面积为0.824，血清Smad5 mRNA预测急性肾衰竭血液透析患者预后的AUC为0.851，二者联合预测急性肾衰竭血液透析患者预后的AUC为0.930，二者联合优于血清miR-155和Smad5 mRNA各自单独预测（Z联合vs miR-155 = 3.543、Z联合vs Smad5 mRNA = 4.325，P均＜0.05）。
      结论  miR-155高表达和Smad5低表达是影响急性肾衰竭血液透析患者预后的危险因素，二者联合检测可以更好地评估患者的预后情况。

       

      Abstract:
      Objective  To explore the prognostic value of serum levels of miR-155 and Smad5 in hemodialysis (HD) patients with acute renal failure (ARF).
      Methods  From August 2018 to July 2019, 120 ARF patients on HD were selected as study group while another 116 healthy subjects as control group; the serum expressions of miR-155 and Smad5 mRNA were detected by quantitative reverse transcriptase-mediated polymerase chain reaction (qRT-PCR). Pearson’s method was utilized for examining the correlation between serum expression levels of miR-155 and Smad5 mRNA and the levels of creatinine and blood urea nitrogen (BUN); Kaplan-Meier method was employed for examining the survival of HD patients with ARF; COX regression for analyzing the prognostic factors; receiver operating characteristic curve (ROC) curve for assessing the predictive value of serum miR-155 and Smad5 mRNA levels.
      Results  The levels of serum miR-155, creatinine and BUN were obviously higher in study group than those in control group (P<0.05). And the level of Smad5 mRNA was obviously lower than that in control group (P<0.05). According to Pearson’s correlation analysis, the serum levels of miR-155 and Smad5 mRNA were correlated negatively (r=−0.538, P<0.05). The expression level of serum miR-155 was correlated positively with the levels of creatinine and BUN (r=0.489, 0.532, both P<0.05). The serum expression level of Smad5 mRNA was correlated negatively with the levels of creatinine and BUN (r=−0.475, −0.558, both P<0.05). The serum levels of miR-155, creatinine and BUN were obviously lower in survival group than those in death group (P<0.05). And the expression level of Smad5 mRNA was obviously higher than that in death group (P<0.05). According to Kaplan-Meier survival curve analysis, the survival rate of miR-155 high-expression group was obviously lower than that of low-expression group (χ2=4.219, P=0.040). And the survival rate of Smad5 high mRNA expression group was obviously higher than that of Smad5 low mRNA expression group (χ2=7.590, P=0.006). According to COX regression analysis, miR-155, Smad5 mRNA, creatinine and BUN were risk factors affecting the prognosis of HD patients with ARF (P<0.05). AUC of serum miR-155 in predicting the prognosis was 0.824, AUC of serum Smad5 mRNA 0.851 and AUC of both 0.930, combining both methods was superior to the prediction of serum miR-155 and Smad5 mRNA separately (Z combination vs miR-155=3.543, Z combination vs Smad5 mRNA=4.325, P<0.05）.
      Conclusions  A high expression of miR-155 and a low expression of Smad5 are risk factors affecting the prognosis of HD patients with ARF. And a co-detection of miR-155 and Smad5 may better evaluate the prognosis of HD patients with ARF.

       

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