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

Subagini Nagarajah; Marianne Rasmussen; Silje V. Hoegh; Martin Tepel

doi:10.1016/j.ekir.2020.09.005

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

Subagini Nagarajah, Marianne Rasmussen, Silje V. Hoegh, Martin Tepel^*

^*Corresponding author for this work

University of Southern Denmark

Research output: Contribution to journal › Journal article › Research › peer-review

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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 non-coding 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^–6 to indicate viremia after transplantation. Samples for 11 of 66 renal transplant recipients (17%) with MGAT3-AS1/beta-actin ratios below 4.45 × 10^–6 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^–6 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.

Original language	English
Journal	Kidney International Reports
Volume	5
Issue number	12
Pages (from-to)	2218-2227
Number of pages	10
ISSN	2468-0249
DOIs	https://doi.org/10.1016/j.ekir.2020.09.005 https://doi.org/10.1016/j.ekir.2020.09.005
Publication status	Published - Dec 2020

Keywords

BK polyomavirus
cytomegalovirus
living-donor renal transplant recipients
long non-coding RNA

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Open Access VersionFinal published version, 463 KBLicence: CC BY-NC-ND

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@article{2b2b037fb2114ed191b77f7d566e55ab,

title = "Prospective Study of Long Non-Coding RNA, MGAT3-AS1, and Viremia of BK Polyomavirus and Cytomegalovirus in Living Donor Renal Transplant Recipients",

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 non-coding 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 × 10–6 to indicate viremia after transplantation. Samples for 11 of 66 renal transplant recipients (17%) with MGAT3-AS1/beta-actin ratios below 4.45 × 10–6 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 × 10–6 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.",

keywords = "BK polyomavirus, cytomegalovirus, living-donor renal transplant recipients, long non-coding RNA",

author = "Subagini Nagarajah and Marianne Rasmussen and Hoegh, {Silje V.} and Martin Tepel",

year = "2020",

month = dec,

doi = "10.1016/j.ekir.2020.09.005",

language = "English",

volume = "5",

pages = "2218--2227",

journal = "Kidney International Reports",

issn = "2468-0249",

publisher = "Elsevier",

number = "12",

}

Prospective Study of Long Non-Coding RNA, MGAT3-AS1, and Viremia of BK Polyomavirus and Cytomegalovirus in Living Donor Renal Transplant Recipients. / Nagarajah, Subagini; Rasmussen, Marianne; Hoegh, Silje V. et al.
In: Kidney International Reports, Vol. 5, No. 12, 12.2020, p. 2218-2227.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Prospective Study of Long Non-Coding RNA, MGAT3-AS1, and Viremia of BK Polyomavirus and Cytomegalovirus in Living Donor Renal Transplant Recipients

AU - Nagarajah, Subagini

AU - Rasmussen, Marianne

AU - Hoegh, Silje V.

AU - Tepel, Martin

PY - 2020/12

Y1 - 2020/12

N2 - 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 non-coding 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 × 10–6 to indicate viremia after transplantation. Samples for 11 of 66 renal transplant recipients (17%) with MGAT3-AS1/beta-actin ratios below 4.45 × 10–6 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 × 10–6 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.

AB - 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 non-coding 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 × 10–6 to indicate viremia after transplantation. Samples for 11 of 66 renal transplant recipients (17%) with MGAT3-AS1/beta-actin ratios below 4.45 × 10–6 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 × 10–6 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.

KW - BK polyomavirus

KW - cytomegalovirus

KW - living-donor renal transplant recipients

KW - long non-coding RNA

U2 - 10.1016/j.ekir.2020.09.005

DO - 10.1016/j.ekir.2020.09.005

M3 - Journal article

C2 - 33305115

AN - SCOPUS:85093669618

SN - 2468-0249

VL - 5

SP - 2218

EP - 2227

JO - Kidney International Reports

JF - Kidney International Reports

IS - 12

ER -

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

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Keywords

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