Prospective Study of Long Noncoding 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 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^-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 noncoding RNA.

Graphical abstract

Figure 1

Scatter diagram showing long noncoding RNA, β-1,4-mannosylglycoprotein 4-β-N-acetylglucosaminyl-transferaseantisense-1 (MGAT3-AS1)/beta-actin ratio in peripheral blood mononuclear cells from 163 living donor renal transplant recipients with and without posttransplant viremia during the first postoperative month. Median levels are indicated by vertical lines.

Figure 2

Long noncoding RNA, β-1,4-mannosylglycoprotein 4-β-N-acetylglucosaminyl-transferaseantisense-1 (MGAT3-AS1)/beta-actin ratio in peripheral blood mononuclear cells from 163 living-donor renal transplant recipients during the first postoperative month. (a) Scatter diagram showing MGAT3-AS1/beta-actin ratio in recipients with induction therapy consisting of basiliximab (Ba; median, 6.21 × 10^–6; IQR, 4.47 × 10^–6 to 10.07 × 10^–6; n = 91); basiliximab and prednisolone (BaPre; median, 8.84 × 10^–6; IQR, 7.50 × 10^–6 to 10.18 × 10^–6; n = 2); basiliximab, rituximab, and prednisolone (BaRiPre; median, 2.62 ×10^–6; IQR, 1.94 × 10^–6 to 4.82 × 10^–6; n = 21); rituximab and prednisolone (RiPre; median, 4.25 × 10^–6; IQR, 1.81 × 10^–6 to 5.28 × 10^–6; n = 19); rituximab, prednisolone, and thymoglobulin (RiPreTGL; median, 2.87 × 10^–6; IQR, 1.71∗10^–6 to 4.06 × 10^–6; n = 23); thymoglobuline (TGL; median, 21.67 × 10^–6; n = 2); prednisolone and thymoglobulin (PreTGL; median, 12.31 × 10^–6, IQR, 8.06 × 10^–6 to 113.63 × 10^–6; n = 5). Median levels were indicated by vertical lines. The dotted line indicates the median level for the induction therapy with basiliximab. ∗∗ indicates P < 0.01 between the groups as assessed by Kruskal-Wallis test and Dunn multiple comparisons test. (b) Histogram of MGAT3-AS1/beta-actin ratio in recipients with induction therapy containing rituximab (n = 63 and other induction therapy (n = 100). Most recipients with induction therapy containing rituximab had levels below –4.45 (red bars) whereas recipients with other induction therapy showed levels ranging from –5.8 to –4.2. (c) Receiver operator characteristics curve showing that the MGAT3-AS1/beta-actin ratio characterizes the immunosuppressive regime containing rituximab. The curve indicates that MGAT3-AS1/beta-actin ratio characterizes the immunosuppressive regime containing rituximab. Area under curve, 0.82 (95 percent confidence interval: 0.76–0.89; P < 0.001). IQR, Interquartile range; MGAT3-AS1 Long noncoding RNA, β-1,4-mannosylglycoprotein 4-β-N-acetylglucosaminyl-transferase antisense-1.