Abstract:

Objective　To investigate the relationship of the levels of miR-150-5p and miR-135b in peripheral blood with urinary albumin excretion rate (UAER) and prognosis in patients with diabetic nephropathy (DN). Methods　The prospective research method was used. Eighty-five patients with DN admitted to Hospital Affiliated to Yan'an University from January 2019 to October 2021 were selected as a DN group, including 46 men and 39 women; they were (46.28±4.41) years old; their duration of type 2 diabetes (T2DM) was (7.24±2.31) years. Seventy-six patients with T2DM were selected as a T2DM group, including 40 men and 36 women; they were (44.95 ± 6.13) years old; their duration of T2DM was (6.98±3.28) years. Eighty healthy people were selected as a control group, including 43 men and 37 women; they were (45.74±5.68) years old. The clinical data and levels of miR-150-5p and miR-135b in peripheral blood of the 3 groups were collected. The correlation of each indicator with UAER was analyzed by the Spearman analysis. The receiver operating characteristic curves (ROC) were drawn and the areas under the curves (AUC) were calculated to analyze the predictive efficacy of each indicator for the prognosis. Relative risk (RR) and 95% confidence interval (CI) were used to analyze the impact of each indicator on prognosis. Results　The levels of peripheral blood miR-150-5p and miR-135b in the DN group were both higher than those in the T2DM group, which were higher than those in the control group [(3.36±0.68) vs. (1.03±0.62) vs. (0.78±0.21) and (3.96±0.51) vs. (1.24±0.48) vs. (0.66±0.12)], with statistical differences (F=560.11 and 1 519.26, both P<0.05). The levels of peripheral blood miR-150-5p and miR-135b in the patients with UAER>300 mg/24 h were both higher than those in the patients with UAER 30-300 mg/24 h, which were higher than those in the patients with UAER<30 mg/24 h [(4.10±0.92) vs. (3.42±0.64) vs. (2.73±0.51) and (5.40±0.87) vs. (3.87±0.61) vs. (3.02±0.49)], with statistical differences (F=23.53 and 78.25; both P<0.05).The levels of peripheral blood miR-150-5p and miR-135b in the DN patients were positively correlated with UREA (r=0.783 and 0.835; both P<0.05). After 12 months' follow-up, 15 patients developed ESRD; the levels of peripheral blood miR-150-5p and miR-135b in the patients with ESRD were higher than those in the patients without ESRD [(4.41±0.55) vs. (3.14±0.38) and (4.67±0.61) vs. (3.81±0.42)], with statistical differences (t=10.67 and 6.53; both P<0.05). The AUC's of peripheral blood miR-150-5p, miR-135b, and their combination in the prediction of ESRD in the DN patients were 0.733, 0.829, and 0.944, respectively. The RR of ESRD in the patients with high levels of peripheral blood miR-150-5p and miR-135b was 3.619 times and 10.889 times higher than that in the patients with low levels, with the 95%CI of 1.105-11.856 and 1.503-78.872, respectively. Conclusions　The levels of miR-150-5p and miR-135b in peripheral blood are positively correlated with UAER in patients with DN. The combined detection can be used as an important auxiliary means to predict ESRD in patients with DN, and provide reliable data support for clinical diagnosis and treatment.

Key words:

Diabetic nephropathy, Peripheral blood, MiR-150-5p, MiR-135b, Urinary microalbumin excretion rate, Prognosis

摘要：

目的　探讨外周血miR-150-5p、miR-135b水平与糖尿病肾病（DN）患者尿白蛋白排泄率（UAER）、预后的关系。方法　采用前瞻性研究方法，选取2019年1月至2021年10月延安大学附属医院收治的85例DN患者作为DN组［男46例，女39例，年龄（46.28±4.41）岁，2型糖尿病（T2DM）病程（7.24±2.31）年］，另纳入76例单纯T2DM患者作为T2DM组［男40例，女36例，年龄（44.95±6.13）岁，T2DM病程（6.98±3.28）年］，80例健康体检者作为对照组［男43例，女37例，年龄（45.74±5.68）岁］。收集3组患者临床资料及外周血miR-150-5p、miR-135b水平，Spearman分析各指标与UAER相关性，绘制受试者操作特征曲线（ROC）及曲线下面积（AUC），分析各指标预后的预测效能，采用相对危险度（RR）及95%置信区间（CI）分析各指标对预后的影响。结果　DN组外周血miR-150-5p、miR-135b水平>T2DM组>对照组［（3.36±0.68）比（1.03±0.62）比（0.78±0.21）、（3.96±0.51）比（1.24±0.48）比（0.66±0.12）］，差异均有统计学意义（F=560.11、1 519.26，均P<0.05）；DN组UAER>300 mg/24 h患者外周血miR-150-5p、miR-135b水平>UAER 30～300 mg/24 h患者>UAER<30 mg/24 h患者［（4.10±0.92）比（3.42±0.64）比（2.73±0.51）、（5.40±0.87）比（3.87±0.61）比（3.02±0.49）］，差异均有统计学意义（F=23.53、78.25，均P<0.05）；DN患者外周血miR-150-5p、miR-135b水平与UREA呈正相关（r=0.783、0.835，均P<0.05）；随访12个月，15例发生终末期肾病（ESRD），发生ESRD患者外周血miR-150-5p、miR-135b水平均高于未发生ESRD患者［（4.41±0.55）比（3.14±0.38）、（4.67±0.61）比（3.81±0.42）］，差异均有统计学意义（t=10.67、6.53，均P<0.05）；外周血miR-150-5p、miR-135b、联合预测DN并发ESRD的AUC分别为0.733、0.829、0.944。外周血miR-150-5p、miR-135b高水平患者并发ESRD的RR分别为低水平的3.619倍、10.889倍，其95%CI分别为1.105～11.856、1.503～78.872。结论　外周血miR-150-5p、miR-135b水平与DN患者UAER呈正相关，联合检测可作为预测DN并发ESRD的重要辅助手段，为临床诊治提供可靠数据支持。

关键词:

糖尿病肾病, 外周血, miR-150-5p, miR-135b, 尿白蛋白排泄率, 预后