肾病综合征患者尿液外泌体microRNA-146a、microRNA-200p表达与肾损伤的关系

Relationship between urinary exosome microRNA-146a and microRNA-200p expression levels and renal function injury in patients with nephrotic syndrome

摘要:

目的 探讨肾病综合征（NS）患者尿液外泌体microRNA-146a（miR-146a）、microRNA-200p（miR-200p）表达与肾损伤的关系。方法 选取2019年8月—2022年8月成都大学附属医院收治的106例NS患者为观察组，另选取120例同期来医院体检的健康者为对照组。根据NS患者是否发生肾损伤分为非损伤组74例和损伤组32例。采用实时荧光定量聚合酶链反应检测研究对象的尿液外泌体miR-146a、miR-200p表达。采用受试者工作特征（ROC）曲线评估miR-146a、miR-200p对NS患者肾损伤的诊断效能；采用Pearson法分析尿液外泌体miR-146a、miR-200p与肾功能指标的相关性；采用多因素Logistic逐步回归模型分析影响NS患者肾损伤的相关因素。结果 观察组尿液外泌体miR-146a表达高于对照组（P <0.05），miR-200p表达低于对照组（P <0.05）。非损伤组尿液外泌体miR-146a表达低于损伤组（P <0.05），miR-200p表达高于损伤组（P <0.05）。miR-146a、miR-200p诊断NS患者肾损伤的曲线下面积（AUC）分别为0.873（95% CI：0.822，0.924）、0.844（95% CI：0.793，0.895），最佳截断值分别为4.08和1.99，特异性分别为67.57%和60.81%，敏感性分别为93.75%和93.75%，两者联合诊断的AUC为0.927（95% CI：0.896，0.958），特异性为85.14%，敏感性为87.50%。非损伤组与损伤组的尿蛋白量、白蛋白、肾小球滤过率、尿素氮、血肌酐、血尿酸比较，差异有统计学意义（P <0.05）。Pearson相关性分析结果显示，尿液外泌体miR-146a表达与尿蛋白量、尿素氮、血肌酐呈正相关（r =0.402、0.447和0.613，均P =0.000），与白蛋白、肾小球滤过率呈负相关（r =-0.369和-0.415，均P =0.000）；尿液外泌体miR-200p表达与尿蛋白量、尿素氮、血肌酐呈负相关（r =-0.357、-0.405和-0.534，均P =0.000），与白蛋白、肾小球滤过率呈正相关（r =0.428和0.513，P =0.000）。多因素Logistic逐步回归分析结果显示，肾小球滤过率降低［O^R=2.591（95% CI：1.687，3.980）］、血肌酐升高［O^R=2.342（95% CI：1.576，3.480）］、miR-146a ≥ 4.08［O^R=3.050（95% CI：1.913，4.862）］、miR-200p≤1.99［O^R=3.347（95% CI：2.083，5.378）］是NS患者肾损伤的危险因素（P <0.05）。结论 尿液外泌体miR-146a、miR-200p异常表达与NS患者肾损伤有关，可作为诊断NS患者肾损伤的生物学指标，且两者联合的诊断效能更好，具有临床推广价值。

Abstract:

Objective To explore the relationship between urinary exosomal microRNA-146a (miR-146a) and microRNA-200p (miR-200p) expression levels and renal function injury in patients with nephrotic syndrome (NS).Methods A total of 106 NS cases admitted to our hospital from August 2019 to August 2022 were selected as the observation group, and 120 healthy people who came to our hospital for physical examination during the same period were selected as the control group. NS cases were divided into non-injured group (n = 74) and injured group (n = 32) according to whether renal function was damaged or not. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of miR-146a and miR-200p in urine exosomes. ROC was used to evaluate the diagnostic value of miR-146a and miR-200p on renal injury in NS cases. Pearson correlation analysis was used to explore the relationship between miR-146a, miR-200p in urinary exocrine body and renal function indicators. Multivariate Logistic regression analysis was used to explore the related factors affecting renal function injury in NS cases.Results The level of urine exosome miR-146a in the observation group was higher than that in the control group (P < 0.05), and the level of miR-200p was lower than that in the control group (P <0.05). The level of urine exosome miR-146a in the non-injured group was lower than that in the injured group (P < 0.05), and the level of miR-200p was higher than that in the injured group (P < 0.05). The AUC of miR-146a and miR-200p to predict renal dysfunction in NS patients were 0.873 (95% CI: 0.822, 0.924) and 0.844 (95% CI: 0.793, 0.895), respectively, with cut-off values of 4.08 and 1.99, and specificity of 67.57% and 60.81%, respectively, and sensitivity of 93.75% and 93.75%, respectively. The combined prediction AUC, specificity and sensitivity were 0.927 (95% CI: 0.896, 0.958), 85.14% and 87.50% respectively. The levels of urinary protein, albumin, glomerular filtration rate, urea nitrogen, serum creatinine and serum uric acid in the non-injured group were significantly different from those in the injured group (P < 0.05). Pearson correlation analysis showed that urine exocrine miR-146a was positively correlated with urinary protein, urea nitrogen and serum creatinine (r = 0.402, 0.447 and 0.613, all P = 0.000), and negatively correlated with albumin and glomerular filtration rate (r = -0.369 and -0.415, all P = 0.000), and urine exocrine miR-200p was negatively correlated with urinary protein, urea nitrogen and serum creatinine (r = -0.357, -0.405 and -0.534, all P = 0.000), and positively correlated with albumin and glomerular filtration rate (r = 0.428 and 0.513, P = 0.000). Multivariate Logistic regression analysis showed that glomerular filtration rate decreased [O^R = 2.591 (95% CI: 1.687, 3.980) ], serum creatinine increased [O^R = 2.342 (95% CI: 1.576, 3.480) ], miR-146a ≥ 4.08 [O^R = 3.050 (95% CI: 1.913, 4.862) ], miR-200p ≤ 1.99 [O^R = 3.347 (95% CI: 2.083, 5.378) ] were risk factors for renal dysfunction in NS cases (P < 0.05).Conclusion Abnormal expressions of urine exosome miR-146a and miR-200p are related to renal function injury in NS patients, and can be used as biological indicators to predict renal function injury in NS patients, and the combined diagnosis of the two has better predictive efficacy, and has clinical promotion value.