尿液miR-30a-5p预测激素治疗局灶节段性肾小球硬化的疗效

Urinary miR-30a-5p predict treatment response of corticosteroid in patients with focal segmental glomerulosclerosis

目的:前期研究已经证实尿液miR-30a-5p、miR-196a及miR-490的水平与局灶节段性肾小球硬化(FSGS)的关系密切,本研究旨在探讨尿液miRNAs水平与FSGS患者激素治疗反应间的关系。方法:同时回顾性和前瞻性分析接受激素治疗的原发性FSGS患者,分别观察治疗前后和随访过程中尿液中miRNAs水平和尿蛋白定量,分析尿液miRNAs与尿蛋白变化之间的规律关系。结果:回顾性分析139例FSGS患者,68例经激素治疗后完全缓解(CR组),71例患者经治疗未完全缓解(non-CR组)。治疗前两组患者的性别、年龄和尿蛋白、血清肌酐、总胆固醇水平相似,尿miR-196a和miR-490水平在两组之间亦无显著差异,CR组的尿miR-30a-5p水平显著低于non-CR组(P=0.03)。尿miR-30a-5p的水平能预测FSGS患者对激素治疗的反应(AUC=0.628,P=0.03)。前瞻性观察了55例FSGS患者,激素治疗8周后33例获得CR,尿miR-30a-5p的表达水平随着蛋白尿的缓解而显著下降(P<0.001);而经激素治疗non-CR患者的尿miR-30a-5p水平则与激素治疗无显著关系。进一步前瞻性观察了22例初治的FSGS患者证实,CR组的尿miR-30a-5p的水平随激素治疗逐渐下降(P<0.001);其下降幅度在4周时即与non-CR组即存在显著差异(P=0.003),同期二组尿蛋白的变化尚无明显差异(P=0.29)。结论:尿miR-30a-5p的水平与FSGS激素治疗反应直接相关,并在治疗过程中于尿蛋白之前出现显著变化,可作为预测FSGS激素治疗效果和预后的标志物。

Objective：Previous study showed that there was a close relationship between urinary levels of miR- 196a, miR-30a-Sp, miR-490 and focal segmental glomerulosclerosis （FSGS）. This study aimed to investigate the relationship between urinary miRNAs levels in patients with FSGS and the steroid therapy of FSGS. Methodology：A retrospective cohort analyzed primary FSGS patients treated with steroids. Meanwhile, a prospective cohort analyzed the priamry FSGS patients who were not treated before diagnosis, and then treated with steroids for eight weeks in the study. The urinary levels of miRNAs and proteinuria before treatment, after treatment, and in the middle of the treatment were tested, and the relationship between the levels of miRNAs and proteinuria was investigated. Results：In retrospective cohort, they were 139 patients, 68 patients achieved CR （CR） , while 71 of them did not （non-CR）. Before treatment, the two groups had no significant difference in gender, age, proteinuria, serum creatinine level and cholesterol level. But the urinary level of miR-30a-Sp in the group of non-CR was significantly lower than that in the group of CR （ P = 0. 03 ）. Urinary miR-30a-Sp could marginally predict the response to steroid treatment in FSGS patients （AUC 0. 63, P = 0. 03）. In prospective cohort, they were 55 patients, 33 patients achieved CR （CR） after treatment, while 22 of them did not （non- CR）. The urinary miR-30a-5p level declined as the remission in proteinuria （ P〈0. 001 ）, but in group of non-CR, it did not decrease after steroid therapy. The urinary levels of miRNAs before treatment at fourth and eighth weeks of the treatment were further examined in another 22 patients （ 11 CR vs 11 non-CR）. The urinary levels of miR-30a-5p decreased during the course of treatment in CR group （P〈0. 001）. Differences in urinary miR-30a-5p levels between patients with and without CR were observed at the 4th week of therapy （ P = 0. 003 ） , prior to changes in proteinuria （ P = 0. 29 ）. Conclusion ： The urinary level of miR-30a-5p directly related to the effect of the steroid therapy in patients with FSGS, and could predict the treatment response, and its change was prior to changes in proteinuria. Urinary miR-30a-5p could be used as a new predictive biomarker for prognosis and the treatment response of FSGS.