Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Oct 24, 2017; 7(5): 269-275
Published online Oct 24, 2017. doi: 10.5500/wjt.v7.i5.269
Graft loss among renal-transplant recipients with early reduction of immunosuppression for BK viremia
Marwan M Azar, Roland Assi, Aziz K Valika, David B Banach, Isaac E Hall, Marie-Louise Landry, Maricar F Malinis
Marwan M Azar, Department of Pathology, Section of Microbiology, Massachusetts General Hospital, Boston, MA 02145, United States
Marwan M Azar, Maricar F Malinis, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06510, United States
Roland Assi, Maricar F Malinis, Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, United States
Aziz K Valika, Adventist Health Partners, Chicago, IL 60521, United States
David B Banach, Division of Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06032, United States
Isaac E Hall, Division of Hypertension and Nephrology, University of Utah School of Medicine, Dalt Lake City, UT 84132, United States
Marie-Louise Landry, Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510, United States
Author contributions: Azar MM and Malinis MF analyzed data; Azar MM drafted manuscript; Assi R, Valika AK, Banach DB, Hall IE, Landry ML and Malinis MF revised and edited manuscript; all authors contributed significantly to this work.
Institutional review board statement: The Yale University Institutional Review Board approved this study and all procedures conducted were in accordance with the Helsinki Declaration of 1975.
Conflict-of-interest statement: The authors have no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Marwan M Azar, MD, Microbiology Fellow, Department of Pathology, Section of Microbiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02145, United States. mmazar@mgh.harvard.edu
Telephone: +1-617-6434393 Fax: +1-888-3244639
Received: February 12, 2017
Peer-review started: February 15, 2017
First decision: April 17, 2017
Revised: June 28, 2017
Accepted: August 2, 2017
Article in press: August 2, 2017
Published online: October 24, 2017
Processing time: 252 Days and 8.1 Hours
Abstract
AIM

To review the incidence of graft loss and acute rejection among renal transplant recipients with early reduction of immunosuppression for BK viremia.

METHODS

We performed a retrospective analysis of consecutive de-novo kidney-only transplants from January 2009 to December 2012 to evaluate the incidence of Polyoma-virus associated nephropathy (PyVAN). Recipient plasma was screened for BKV DNA via quantitative polymerase chain reaction (PCR) at months 1, 3, 6, 9 and 12 post-transplant and on worsening graft function. Immunosuppression was reduced at ≥ 3-log copies/mL. Those with viremia of ≥ 4-log copies/mL (presumptive PyVAN) underwent renal transplant biopsy. Presumptive PyVAN (PP) and definitive PyVAN (DP; biopsy-proven) were treated by immunosuppression reduction (IR) only.

RESULTS

Among 319 kidney transplant recipients, the median age was 53 years (range 19-83), 65.8% were male, and 58.9% were white. Biopsy-proven acute rejection was found in 18.5% within 0-168 wk. Death-censored graft loss occurred in 5.3% (n = 17) and graft loss attributable to PyVAN was 0.6% (n = 2). Forty-seven patients were diagnosed with PP (14.7%) and 18 (5.6%) with DP. Graft loss among participants with PyVAN (8.5%) and those without (4.8%) was not significantly different. Deceased donor kidney transplantation (OR = 2.3, 95%CI = 1.1-4.6) and AR (OR = 2.3, 95%CI = 1.2-4.7) were associated with PyVAN in the multivariate analysis. BK viremia between 3 and 4-log copies/mL occurred in 27 patients, all of whom underwent IR. Of these, 16 (59%) never developed PyVAN while 11 (41%) developed PyVAN (4 DP, 7 PP) within a range of 11-39 wk.

CONCLUSION

Instituting an early reduction of immunosuppression, in the absence of adjunctive antivirals, is effective at preventing PyVAN and may be associated with a lower incidence of graft-loss without a reciprocal increase in the incidence of acute rejection.

Keywords: BK virus; Renal transplant; Screening; PyVAN; Prevention; Graft loss

Core tip: The authors describe results of a retrospective study of 319 renal transplant recipients who underwent reduction of immunosuppression for BK viremia at a BK viral of ≥ 3-log copies/mL. Instituting early reduction of immunosuppression in the absence of adjunctive antivirals was effective in reducing the incidence of graft loss due to Polyoma-virus associated nephropathy (PyVAN) without a reciprocal increase in acute rejection. Our study also emphasizes that efforts to implement universal BK virus polymerase chain reaction assay standards recently developed by the World Health Organization are key in establishing a preventative strategy for PyVAN that is widely applicable and highly effective.