利用尿外泌体和微囊泡开发和全国性验证肾移植损伤标志物（日本版的完整英文翻译）。

Development and nationwide validation of kidney graft injury markers using urinary exosomes and microvesicles (complete English translation of the Japanese version).

机构信息

Department of Kidney Transplant Surgery, Sapporo City General Hospital, 1-1 Kita 11-jo Nishi 13-chome, Chuou- ku, Sapporo, Hokkaido, 060-8604, Japan.

Harada Urological Clinic, 4F Hokuyaku Bldg., 1-1 Kita 11-jo Nishi 14-chome, Chuou-ku, Sapporo, Hokkaido, 060-0011, Japan.

出版信息

BMC Nephrol. 2023 Jun 6;24(1):158. doi: 10.1186/s12882-023-03189-z.

DOI:10.1186/s12882-023-03189-z

PMID:37280521

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10242781/

Abstract

BACKGROUND

Non-invasive, prompt, and proper detection tools for kidney graft injuries (KGIs) are awaited to ensure graft longevity. We screened diagnostic biomarkers for KGIs following kidney transplantation using extracellular vesicles (EVs; exosomes and microvesicles) from the urine samples of patients.

METHODS

One hundred and twenty-seven kidney recipients at 11 Japanese institutions were enrolled in this study; urine samples were obtained prior to protocol/episode biopsies. EVs were isolated from urine samples, and EV RNA markers were assayed using quantitative reverse transcription polymerase chain reaction. Diagnostic performance of EV RNA markers and diagnostic formulas comprising these markers were evaluated by comparison with the corresponding pathological diagnoses.

RESULTS

EV CXCL9, CXCL10, and UMOD were elevated in T-cell-mediated rejection samples compared with other KGI samples, while SPNS2 was elevated in chronic antibody-mediated rejection (cABMR) samples. A diagnostic formula developed through Sparse Logistic Regression analysis using EV RNA markers allowed us to accurately (with an area under the receiver operator characteristic curve [AUC] of 0.875) distinguish cABMR from other KGI samples. EV B4GALT1 and SPNS2 were also elevated in cABMR, and a diagnostic formula using these markers was able to distinguish between cABMR and chronic calcineurin toxicity accurately (AUC 0.886). In interstitial fibrosis and tubular atrophy (IFTA) urine samples and those with high Banff chronicity score sums (BChS), POTEM levels may reflect disease severity, and diagnostic formulas using POTEM detected IFTA (AUC 0.830) and high BChS (AUC 0.850).

CONCLUSIONS

KGIs could be diagnosed with urinary EV mRNA analysis with relatively high accuracy.

摘要

背景

为了确保移植物的长期存活，需要寻找非侵入性、快速且合适的肾移植后移植物损伤（KGl）检测工具。我们从患者的尿液样本中筛选了用于检测肾移植后 KGl 的诊断生物标志物，即细胞外囊泡（EV；外泌体和微泡）。

方法

本研究共纳入了 11 家日本机构的 127 名肾移植受者，他们在进行方案/发作活检前采集了尿液样本。从尿液样本中分离 EV，并使用实时定量逆转录聚合酶链反应（qRT-PCR）检测 EV RNA 标志物。通过与相应的病理诊断比较，评估 EV RNA 标志物和包含这些标志物的诊断公式的诊断性能。

结果

与其他 KGl 样本相比，T 细胞介导的排斥反应样本中 EV CXCL9、CXCL10 和 UMOD 升高，而慢性抗体介导的排斥反应（cABMR）样本中 SPNS2 升高。通过稀疏逻辑回归分析 EV RNA 标志物建立的诊断公式可以准确地区分 cABMR 与其他 KGl 样本（曲线下面积 [AUC] 为 0.875）。EV B4GALT1 和 SPNS2 在 cABMR 中也升高，使用这些标志物的诊断公式能够准确地区分 cABMR 与慢性钙调神经磷酸酶毒性（AUC 0.886）。在间质纤维化和肾小管萎缩（IFTA）尿液样本和高 Banff 慢性评分总和（BChS）样本中，POTEM 水平可能反映疾病的严重程度，使用 POTEM 的诊断公式可以检测到 IFTA（AUC 0.830）和高 BChS（AUC 0.850）。