Kocyigit Ismail, Taheri Serpil, Sener Elif Funda, Eroglu Eray, Ozturk Fahir, Unal Aydin, Korkmaz Kezban, Zararsiz Gokmen, Sipahioglu Murat Hayri, Ozkul Yusuf, Tokgoz Bulent, Oymak Oktay, Ecder Tevfik, Axelsson Jonas
Department of Internal Medicine, Division of Nephrology, Erciyes University Medical Faculty, Kayseri, Turkey.
Department of Medical Biology, Erciyes University Medical Faculty, Kayseri, Turkey.
BMC Nephrol. 2017 May 30;18(1):179. doi: 10.1186/s12882-017-0600-z.
Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder with unclear disease mechanism. Currently, overt hypertension and increased renal volume are the best predictors of renal function. In this study, we assessed the usefulness of selected circulating microRNAs (miRs) to predict disease progress in a cohort with ADPKD.
Eighty ADPKD patients (44.6 ± 12.7 years, 40% female, 65% hypertensive) and 50 healthy subjects (HS; 45.4 ± 12.7, 44% female) were enrolled in the study. Serum levels of 384 miRs were determined by Biomark Real Time PCR. Groups were compared using the limma method with multiple-testing correction as proposed by Smyth (corrected p < 0.01 considered significant).
Comparing ADPKD to HS, we found significant differences in blood levels of 18 miRs (3 more and 15 less abundant). Of these, miR-3907, miR-92a-3p, miR-25-3p and miR-21-5p all rose while miR-1587 and miR-3911 decreased as renal function declined in both cross-sectional and longitudinal analysis. Using ROC analysis, an increased baseline miR-3907 in the circulation predicted a > 10% loss of GFR over the following 12 months (cut-off >2.2 AU, sensitivity 83%, specificity 78%, area 0.872 [95% CI: 0.790-0.953, p < 0.001]). Adjusting for age and starting CKD stage using multiple binary logistic regression analysis did not abrogate the predictive value.
Increased copy numbers of miR-3907 in the circulation may predict ADPKD progression and suggest pathophysiological pathways worthy of further study.
常染色体显性遗传性多囊肾病（ADPKD）是一种常见的遗传性疾病，其发病机制尚不清楚。目前，明显的高血压和肾脏体积增大是肾功能的最佳预测指标。在本研究中，我们评估了特定循环微小RNA（miR）对ADPKD队列疾病进展的预测作用。
本研究纳入了80例ADPKD患者（年龄44.6±12.7岁，女性占40%，高血压患者占65%）和50名健康受试者（HS；年龄45.4±12.7岁，女性占44%）。采用Biomark实时PCR法测定384种miR的血清水平。使用Smyth提出的limma方法进行多检验校正后对组间进行比较（校正p<0.01认为具有显著性）。
将ADPKD患者与健康受试者进行比较，我们发现18种miR的血液水平存在显著差异（3种表达增加，15种表达减少）。其中，在横断面和纵向分析中，随着肾功能下降，miR-3907、miR-92a-3p、miR-25-3p和miR-21-5p均升高，而miR-1587和miR-3911降低。通过ROC分析，循环中基线miR-3907升高预测在接下来的12个月内肾小球滤过率（GFR）下降>10%（截断值>2.2 AU，敏感性83%，特异性78%，曲线下面积0.872 [95%CI：0.790-0.953，p<0.001]）。使用多元二元逻辑回归分析对年龄和起始慢性肾脏病（CKD）分期进行校正后，并未消除其预测价值。
循环中miR-3907拷贝数增加可能预测ADPKD进展，并提示了值得进一步研究的病理生理途径。
