Urinary sediment miRNAs reflect tubulointerstitial damage and therapeutic response in IgA nephropathy.
Urinary sediment miRNAs reflect tubulointerstitial damage and therapeutic response in IgA nephropathy.
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DOI：
10.1186/s12882-017-0482-0
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发表时间：
2017-02-15
期刊：
影响因子：
2.3
通讯作者：
Chen XM
中科院分区：
文献类型：
--
作者：
Liang S;Cai GY;Duan ZY;Liu SW;Wu J;Lv Y;Hou K;Li ZX;Zhang XG;Chen XM
免疫球蛋白A肾病（IgAN）是世界上最常见的肾小球肾炎。IgAN的临床表现从轻微的泌尿系统异常到快速进展性肾衰竭不等。由于其侵入性的过程，通过反复肾活检来评估疾病是不实际的。尿沉积物mirna有望作为评估IgAN肾损伤的非侵入性生物标志物。52名活检证实的IgAN患者和25名健康对照者参加了这项研究。提取尿沉积物mirna。实时定量聚合酶链反应（RT-QPCR）检测miR-34a、miR-205、miR-21、miR-146a和miR-155的表达。采用受试者工作特征（ROC）曲线探讨mirna在预测IgAN诊断和评估组织病理学损伤方面的价值。患者根据肾脏疾病：改善全球预后（KDIGO）指南进行治疗并随访。分析mirna在反映治疗效果和疾病进展中的作用。1. IgAN组的尿miR-34a、miR-205和miR-155水平显著低于对照组，但miR-21水平高于对照组。ROC显示，尿miR-34a≤0.047,miR-205≤0.209,miR-21≥0.461,miR-155≤0.002可以区分IgAN患者和健康患者。此外，miR-205≤0.125和miR-21≥0.891可区分IgAN患者中重度小管萎缩/间质纤维化和轻度小管萎缩/间质纤维化。2. 平均随访15.19个月后，蛋白尿的减少（g/24 h/年）与基线尿miR-21呈正相关，与miR-205呈负相关。完全缓解组基线eGFR和miR-205水平显著高于非完全缓解组（p < 0.001; p = 0.018），而蛋白尿、miR-21和miR-146a水平低于非完全缓解组（p = 0.002; p = 0.021; p = 0.009）。但多变量分析显示，只有基线eGFR与IgAN缓解相关（p = 0.001, OR = 1.042）。一些尿沉积物mirna的水平，特别是基线miR-21和miR-205，可能被用作评估IgAN小管间质损伤的潜在预后标志物。此外，尿mirna的基线水平可能是治疗效果和疾病进展的预测指标。本文的在线版本（doi:10.1186/s12882-017-0482-0）包含补充材料，可供授权用户使用。
Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The clinical spectrum of IgAN varies from minor urinary abnormalities to rapidly progressive renal failure. Evaluation of the disease by repeated renal biopsy is not practical due to its invasive procedure. Urinary sediment miRNAs promise to serve as non-invasive biomarkers to assess kidney injury of IgAN. Fifty two biopsy-proven IgAN patients and twenty five healthy controls were enrolled in the study. Urinary sediment miRNAs were extracted. Expressions of miR-34a, miR-205, miR-21, miR-146a and miR-155 were quantified by real-time quantitative polymerase chain reaction (RT-QPCR). The receiver operating characteristic (ROC) curve was used to investigate the value of the miRNAs for predicting diagnosis of IgAN and evaluating histopathological injury. The patients were treated according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and followed up. The roles of miRNAs in reflecting therapeutic efficacy and disease progression were analyzed. 1. The IgAN group had significantly lower urinary miR-34a, miR-205, and miR-155, but higher miR-21 levels than controls. The ROC revealed that urinary miR-34a ≤ 0.047, miR-205 ≤ 0.209, miR-21 ≥ 0.461 and miR-155 ≤ 0.002 could distinguish patients with IgAN from healthy ones. In addition, miR-205 ≤ 0.125 and miR-21 ≥ 0.891 can distinguish IgAN patients with severe tubular atrophy/interstitial fibrosis from those with mild tubular atrophy/interstitial fibrosis. 2. After a mean 15.19 months follow-up, the reduction of proteinuria (g/24 h/year) was positively correlated with baseline urinary miR-21 and inversely correlated with miR-205. The levels of baseline eGFR and miR-205 in the complete remission group were significantly higher than non-complete remission group (p < 0.001; p = 0.018), while proteinuria, miR-21 and miR-146a were lower than non-complete remission group (p = 0.002; p = 0.021; p = 0.009). But multivariate analysis revealed that only baseline eGFR correlated with the remission of IgAN (p = 0.001, OR = 1.042). The levels of some urinary sediment miRNAs, especially baseline miR-21 and miR-205, may be used as potential prognostic markers for evaluating the tubulointerstitial damage of IgAN. Furthermore, baseline levels of urinary miRNAs may be predictors of therapeutic efficacy and disease progression. The online version of this article (doi:10.1186/s12882-017-0482-0) contains supplementary material, which is available to authorized users.