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活体供肾移植受者中长链非编码RNA、MGAT3-AS1与BK多瘤病毒和巨细胞病毒病毒血症的前瞻性研究。

Prospective Study of Long Noncoding RNA, MGAT3-AS1, and Viremia of BK Polyomavirus and Cytomegalovirus in Living Donor Renal Transplant Recipients.

作者信息

Nagarajah Subagini, Rasmussen Marianne, Hoegh Silje V, Tepel Martin

机构信息

Department of Nephrology, Odense University Hospital, Odense, Denmark.

Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark.

出版信息

Kidney Int Rep. 2020 Sep 6;5(12):2218-2227. doi: 10.1016/j.ekir.2020.09.005. eCollection 2020 Dec.

Abstract

INTRODUCTION

Viremia after renal transplantation is a major cause of morbidity and mortality and treatment opportunities are limited. Tests to determine the increased risk for viremia would be preferable.

METHODS

In a prospective, single-center study, we conducted follow-up of 163 renal transplant recipients after incident living donor renal transplantation. We determined a long noncoding RNA, β-1,4-mannosylglycoprotein 4-β-N-acetylglucosaminyltransferase-antisense1 (MGAT3-AS1/beta-actin ratio), in peripheral blood mononuclear cells. Viremia of BK polyomavirus and cytomegalovirus was diagnosed with more than 1000 plasma copies/ml within the first 3 postoperative months. The MGAT3-AS1/beta-actin ratio was assessed before viremia was determined.

RESULTS

Receiver operator characteristics curve analysis showed a median MGAT3-AS1/beta-actin ratio cutoff value of 4.45 × 10 to indicate viremia after transplantation. Samples for 11 of 66 renal transplant recipients (17%) with MGAT3-AS1/beta-actin ratios below 4.45 × 10 showed viremia of BK polyomavirus and cytomegalovirus compared with only 6 of 97 renal transplant recipients (6%) with higher MGAT3-AS1/beta-actin ratios (odds ratio [OR]: 3.03; 95% confidence interval [CI]: 1.06-8.67 by Fisher exact test). Furthermore, samples for 6 of 66 renal transplant recipients (9%) with MGAT3-AS1/beta-actin ratios below 4.45 × 10 showed BK polyomavirus viremia compared with none of 97 renal transplant recipients (0%) with higher MGAT3-AS1/beta-actin ratios (OR: 20.95; 95% CI, 1.16-378.85 by Fisher exact test). Multivariate logistic regression analysis confirmed that MGAT3-AS1/beta-actin ratios below the cutoff level remained significantly associated with viremia after transplant. Lower MGAT3-AS1/beta-actin ratios occurred with rituximab-containing induction therapy.

CONCLUSIONS

A low MGAT3-AS1/beta-actin ratio indicates an increased risk for viremia of BK polyomavirus and cytomegalovirus in living donor renal transplant recipients.

摘要

引言

肾移植后的病毒血症是发病和死亡的主要原因,且治疗机会有限。能够确定病毒血症风险增加的检测方法会更可取。

方法

在一项前瞻性单中心研究中,我们对163例活体供肾肾移植受者进行了随访。我们测定了外周血单个核细胞中一种长链非编码RNA,即β-1,4-甘露糖基糖蛋白4-β-N-乙酰葡糖胺基转移酶反义1(MGAT3-AS1/β-肌动蛋白比值)。BK多瘤病毒和巨细胞病毒血症的诊断标准为术后前3个月内血浆拷贝数超过1000/ml。在确定病毒血症之前评估MGAT3-AS1/β-肌动蛋白比值。

结果

受试者工作特征曲线分析显示,MGAT3-AS1/β-肌动蛋白比值的中位数临界值为4.45×10,以指示移植后的病毒血症。MGAT3-AS1/β-肌动蛋白比值低于4.45×10的66例肾移植受者中有11例(17%)样本出现BK多瘤病毒和巨细胞病毒血症,而MGAT3-AS1/β-肌动蛋白比值较高的97例肾移植受者中只有6例(6%)出现(Fisher精确检验的比值比[OR]:3.03;95%置信区间[CI]:1.06 - 8.67)。此外,MGAT3-AS1/β-肌动蛋白比值低于4.45×10的66例肾移植受者中有6例(9%)样本出现BK多瘤病毒血症,而MGAT3-AS1/β-肌动蛋白比值较高的97例肾移植受者中无一例出现(Fisher精确检验的OR:20.95;95% CI:1.16 - 378.85)。多因素逻辑回归分析证实,低于临界水平的MGAT3-AS1/β-肌动蛋白比值与移植后病毒血症仍显著相关。含利妥昔单抗的诱导治疗会出现较低的MGAT3-AS1/β-肌动蛋白比值。

结论

低MGAT3-AS1/β-肌动蛋白比值表明活体供肾肾移植受者发生BK多瘤病毒和巨细胞病毒血症的风险增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8561/7710814/ce49e1db078a/fx1.jpg

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