BK Polyomavirus Infection in Kidney Transplantation: A Comprehensive Review of Current Challenges and Future Directions

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Dec 17

PMID 39684510

Authors

Nicole Nourie

Celine Boueri

Hoang Tran Minh

Gillian Divard

Carmen Lefaucheur

Maud Salmona

Simon B Gressens

Kevin Louis

Affiliations

Soon will be listed here.

Abstract

BK polyomavirus (BKPyV) infection of the kidney graft remains a major clinical issue in the field of organ transplantation. Risk factors for BKPyV-associated nephropathy (BKPyVAN) and molecular tools for determining viral DNA loads are now better defined. BKPyV DNAemia in plasma, in particular, plays a central role in diagnosing active infection and managing treatment decisions. However, significant gaps remain in the development of reliable biomarkers that can anticipate BKPyV viremia and predict disease outcomes. Biomarkers under active investigation include urine-based viral load assays, viral antigen detection, and immune responses against BKPyV, which may offer more precise methods for monitoring disease progression. In addition, treatment of BKPyVAN is currently based on immunosuppression minimization, while the role of adjunctive therapies remains an area of active research, highlighting the need for more personalized treatment regimens. Ongoing clinical trials are also exploring the efficacy of T-cell-based immunotherapies. The clinical management of BKPyV infection, based on proactive virological monitoring, immune response assessment, integrated histopathology, and timely immunosuppression reduction, is likely to reduce the burden of disease and improve outcomes in kidney transplantation.

References

Haller J, Diebold M, Leuzinger K, Wehmeier C, Handschin J, Amico P . Urine CXCL10 to Assess BK Polyomavirus Replication After Kidney Transplantation. Transplantation. 2023; 107(12):2568-2574. PMC: 10664791. DOI: 10.1097/TP.0000000000004712. View

Almarhabi H, Rotstein C . Symptomatic BK virus cystitis in non-renal transplant recipients. J Assoc Med Microbiol Infect Dis Can. 2022; 4(2):102-107. PMC: 9602953. DOI: 10.3138/jammi.2018-0035. View

Mohammad D, Kim D, Baracco R, Kapur G, Jain A . Treatment of BK virus with a stepwise immunosuppression reduction and intravenous immunoglobulin in pediatric kidney transplant. Pediatr Transplant. 2022; 26(4):e14241. DOI: 10.1111/petr.14241. View

Velay A, Solis M, Benotmane I, Gantner P, Soulier E, Moulin B . Intravenous Immunoglobulin Administration Significantly Increases BKPyV Genotype-Specific Neutralizing Antibody Titers in Kidney Transplant Recipients. Antimicrob Agents Chemother. 2019; 63(8). PMC: 6658761. DOI: 10.1128/AAC.00393-19. View

Bernhoff E, Gutteberg T, Sandvik K, Hirsch H, Rinaldo C . Cidofovir inhibits polyomavirus BK replication in human renal tubular cells downstream of viral early gene expression. Am J Transplant. 2008; 8(7):1413-22. DOI: 10.1111/j.1600-6143.2008.02269.x. View

Loetscher M, Gerber B, Loetscher P, Jones S, Piali L, Clark-Lewis I . Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. J Exp Med. 1996; 184(3):963-9. PMC: 2192763. DOI: 10.1084/jem.184.3.963. View

Salinas T, Li C, Snopkowski C, Stryjniak G, Shankaranarayanan D, Albakry S . Urinary cell mRNA profiling of kidney allograft recipients: Development of a portable protocol for noninvasive diagnosis of T cell mediated rejection and BK virus nephropathy. J Immunol Methods. 2022; 512:113402. DOI: 10.1016/j.jim.2022.113402. View

Gardner S, Field A, Coleman D, HULME B . New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet. 1971; 1(7712):1253-7. DOI: 10.1016/s0140-6736(71)91776-4. View

Kuypers D, Bammens B, Claes K, Evenepoel P, Lerut E, Vanrenterghem Y . A single-centre study of adjuvant cidofovir therapy for BK virus interstitial nephritis (BKVIN) in renal allograft recipients. J Antimicrob Chemother. 2008; 63(2):417-9. DOI: 10.1093/jac/dkn495. View

10.

Kotton C, Kamar N, Wojciechowski D, Eder M, Hopfer H, Randhawa P . The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation. Transplantation. 2024; 108(9):1834-1866. PMC: 11335089. DOI: 10.1097/TP.0000000000004976. View

11.

Krisl J, Taber D, Pilch N, Chavin K, Bratton C, Thomas B . Leflunomide efficacy and pharmacodynamics for the treatment of BK viral infection. Clin J Am Soc Nephrol. 2012; 7(6):1003-9. DOI: 10.2215/CJN.12531211. View

12.

Nickeleit V, Davis V, Thompson B, Singh H . The Urinary Polyomavirus-Haufen Test: A Highly Predictive Non-Invasive Biomarker to Distinguish "Presumptive" from "Definitive" Polyomavirus Nephropathy: How to Use It-When to Use It-How Does It Compare to PCR Based Assays?. Viruses. 2021; 13(1). PMC: 7833404. DOI: 10.3390/v13010135. View

13.

Gately R, Milanzi E, Lim W, Teixeira-Pinto A, Clayton P, Isbel N . Incidence, Risk Factors, and Outcomes of Kidney Transplant Recipients With BK Polyomavirus-Associated Nephropathy. Kidney Int Rep. 2023; 8(3):531-543. PMC: 10014440. DOI: 10.1016/j.ekir.2022.12.020. View

14.

Jackson J, Kim E, Begley B, Cheeseman J, Harden T, Perez S . Urinary chemokines CXCL9 and CXCL10 are noninvasive markers of renal allograft rejection and BK viral infection. Am J Transplant. 2011; 11(10):2228-34. PMC: 3184377. DOI: 10.1111/j.1600-6143.2011.03680.x. View

15.

Liacini A, Seamone M, Muruve D, Tibbles L . Anti-BK virus mechanisms of sirolimus and leflunomide alone and in combination: toward a new therapy for BK virus infection. Transplantation. 2010; 90(12):1450-7. DOI: 10.1097/TP.0b013e3182007be2. View

16.

Kaur A, Wilhelm M, Wilk S, Hirsch H . BK polyomavirus-specific antibody and T-cell responses in kidney transplantation: update. Curr Opin Infect Dis. 2019; 32(6):575-583. DOI: 10.1097/QCO.0000000000000602. View

17.

Rasaei N, Malekmakan L, Gholamabbas G, Abdizadeh P . Comparative Study of Intravenous Immunoglobulin and Leflunomide Combination Therapy With Intravenous Immunoglobulin Single Therapy in Kidney Transplant Patients With BK Virus Infection: Single-Center Clinical Trial. Exp Clin Transplant. 2023; 21(10):814-819. DOI: 10.6002/ect.2023.0071. View

18.

Knowles W, Pipkin P, Andrews N, Vyse A, Minor P, Brown D . Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40. J Med Virol. 2003; 71(1):115-23. DOI: 10.1002/jmv.10450. View

19.

Maung Myint T, Chong C, Wyld M, Nankivell B, Kable K, Wong G . Polyoma BK Virus in Kidney Transplant Recipients: Screening, Monitoring, and Management. Transplantation. 2021; 106(1):e76-e89. DOI: 10.1097/TP.0000000000003801. View

20.

Mosca M, Bacchetta J, Chamouard V, Rascle P, Dubois V, Paul S . IVIg therapy in the management of BK virus infections in pediatric kidney transplant patients. Arch Pediatr. 2023; 30(3):165-171. DOI: 10.1016/j.arcped.2023.01.005. View