多中心、前瞻性、观察性研究：尿液外泌体标志物在肾移植纤维化中的应用。

Multicenter, prospective, observational study for urinary exosomal biomarkers of kidney allograft fibrosis.

机构信息

Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Division of Vascular Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

出版信息

Sci Rep. 2024 Sep 2;14(1):20319. doi: 10.1038/s41598-024-71279-5.

DOI:10.1038/s41598-024-71279-5

PMID:39223169

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11369113/

Abstract

Severity of deceased donor kidney fibrosis impacts graft survival in deceased-donor kidney transplantation. Our aim was to identify potential miRNA biomarkers in urinary exosomes that mirror interstitial fibrosis and tubular atrophy (IFTA) severity. Among 109 urine samples from deceased donors, 34 displayed no IFTA in the zero-day biopsy (No IFTA group), while the remaining 75 deceased donor kidneys exhibited an IFTA score ≥ 1 (IFTA group). After analyzing previous reports and electronic databases, six miRNAs (miR-19, miR-21, miR-29c, miR-150, miR-200b, and miR-205) were selected as potential IFTA biomarker candidates. MiR-21, miR-29c, miR-150, and miR-205 levels were significantly higher, while miR-19 expression was significantly lower in the IFTA group. MiR-21 (AUC = 0.762; P < 0.001) and miR-29c (AUC = 0.795; P < 0.001) showed good predictive accuracy for IFTA. In the No IFTA group, the eGFR level at 1 week after transplantation was significantly higher compared to the IFTA group (41.34 mL/min/1.73m vs. 28.65 mL/min/1.73m, P = 0.012). These findings signify the potential of urinary exosomal miRNAs as valuable biomarker candidates for evaluating the severity of IFTA in deceased donor kidneys before they undergo recovery.

摘要

供体肾纤维化程度影响尸体供肾移植的移植物存活率。我们的目的是确定尿液外泌体中潜在的 miRNA 生物标志物，这些标志物反映了间质纤维化和肾小管萎缩（IFTA）的严重程度。在 109 份来自尸体供者的尿液样本中，34 份在零天活检中无 IFTA（无 IFTA 组），而其余 75 份尸体供肾的 IFTA 评分≥1（IFTA 组）。在分析了之前的报告和电子数据库后，选择了 6 个 miRNA（miR-19、miR-21、miR-29c、miR-150、miR-200b 和 miR-205）作为潜在的 IFTA 生物标志物候选物。miR-21、miR-29c、miR-150 和 miR-205 的水平在 IFTA 组中明显更高，而 miR-19 的表达在 IFTA 组中明显更低。miR-21（AUC=0.762；P<0.001）和 miR-29c（AUC=0.795；P<0.001）对 IFTA 具有良好的预测准确性。在无 IFTA 组中，移植后 1 周时的 eGFR 水平明显高于 IFTA 组（41.34 mL/min/1.73m 比 28.65 mL/min/1.73m，P=0.012）。这些发现表明，尿液外泌体 miRNA 作为评估尸体供肾 IFTA 严重程度的有价值的生物标志物候选物具有潜力，可在其恢复前进行评估。