Risk factors for progression from low level BK dnaemia to unfavorable outcomes after BK management via immunosuppressive reduction.
BK nephropathy
BK viremia
denovo DSA
rejection
Journal
Transplant infectious disease : an official journal of the Transplantation Society
ISSN: 1399-3062
Titre abrégé: Transpl Infect Dis
Pays: Denmark
ID NLM: 100883688
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
revised:
23
12
2020
received:
01
11
2020
accepted:
29
12
2020
pubmed:
6
1
2021
medline:
3
8
2021
entrez:
5
1
2021
Statut:
ppublish
Résumé
Effective management of BK viremia (BKPyV-DNAemia) in kidney transplant recipients (KTRs) involves regular monitoring and adjustment of immunosuppression. With this strategy, the majority of patients will clear BK or have ongoing, but non-significant, low-level BKPyV-DNAemia. However, despite adjustments, some will develop more severe sequelae of BK including BKPyV-DNAemia >5 log This was a single-center study of KTRs transplanted at the University of Wisconsin-Madison between 01/01/2015 and 12/31/2017. In this study, we sought to elucidate characteristics associated with the progression of BKPyV-DNAemia to unfavorable outcomes after decreasing immunosuppressive medications for the management of BK viremia as described in consensus guidelines. A total of 224 KTRs fulfilled our selection criteria; 118 (53%) resolved or had persistent low DNAemia, 64 (28%) had severe BK/nephropathy, and 42 (19%) developed dnDSA or AR. In multivariable analysis, female gender (HR: 2.05; 95% CI: 1.08-3.90; P = .02); previous rejection (HR: 2.90; 95% CI: 1.04-8.12; P = .04), and early infection (HR: 0.81; 95% CI: 0.72-0.90; P < .001) were associated with the development of severe BK/nephropathy. Conversely, non-depleting induction at transplant (HR: 2.06; 95% CI: 1.03-4.11; P = .03), HLA mismatches >3 (HR: 2.27; HR: 1.01-5.06; P = .04), and delayed graft function (HR: 4.14; 95% CI: 1.12-15.28; P = .03) were associated with development of dnDSA and/or rejection. Our study suggests that almost half of KTRs with BKPyV-DNAemia managed by our immunosuppressant adjustment protocol progress unfavorably. Identification of these risk factors could assist the frontline clinician in creating an individualized immunosuppressive modification plan potentially mitigating negative outcomes.
Sections du résumé
BACKGROUNDS
BACKGROUND
Effective management of BK viremia (BKPyV-DNAemia) in kidney transplant recipients (KTRs) involves regular monitoring and adjustment of immunosuppression. With this strategy, the majority of patients will clear BK or have ongoing, but non-significant, low-level BKPyV-DNAemia. However, despite adjustments, some will develop more severe sequelae of BK including BKPyV-DNAemia >5 log
METHODS
METHODS
This was a single-center study of KTRs transplanted at the University of Wisconsin-Madison between 01/01/2015 and 12/31/2017. In this study, we sought to elucidate characteristics associated with the progression of BKPyV-DNAemia to unfavorable outcomes after decreasing immunosuppressive medications for the management of BK viremia as described in consensus guidelines.
RESULTS
RESULTS
A total of 224 KTRs fulfilled our selection criteria; 118 (53%) resolved or had persistent low DNAemia, 64 (28%) had severe BK/nephropathy, and 42 (19%) developed dnDSA or AR. In multivariable analysis, female gender (HR: 2.05; 95% CI: 1.08-3.90; P = .02); previous rejection (HR: 2.90; 95% CI: 1.04-8.12; P = .04), and early infection (HR: 0.81; 95% CI: 0.72-0.90; P < .001) were associated with the development of severe BK/nephropathy. Conversely, non-depleting induction at transplant (HR: 2.06; 95% CI: 1.03-4.11; P = .03), HLA mismatches >3 (HR: 2.27; HR: 1.01-5.06; P = .04), and delayed graft function (HR: 4.14; 95% CI: 1.12-15.28; P = .03) were associated with development of dnDSA and/or rejection.
CONCLUSION
CONCLUSIONS
Our study suggests that almost half of KTRs with BKPyV-DNAemia managed by our immunosuppressant adjustment protocol progress unfavorably. Identification of these risk factors could assist the frontline clinician in creating an individualized immunosuppressive modification plan potentially mitigating negative outcomes.
Substances chimiques
Immunosuppressive Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13561Subventions
Organisme : Virginia Lee Cook Foundation
Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Hirsch HH, Randhawa P; Practice ASTIDCo. BK polyomavirus in solid organ transplantation. Am J Transplant. 2013;13(Suppl 4):179-188.
Jiang M, Abend JR, Johnson SF, Imperiale MJ. The role of polyomaviruses in human disease. Virology. 2009;384(2):266-273.
Knowles WA. Discovery and epidemiology of the human polyomaviruses BK virus (BKV) and JC virus (JCV). Adv Exp Med Biol. 2006;577:19-45.
Kaur A, Wilhelm M, Wilk S, Hirsch HH. BK polyomavirus-specific antibody and T-cell responses in kidney transplantation: update. Curr Opin Infect Dis. 2019;32(6):575-583.
Hirsch HH, Brennan DC, Drachenberg CB, et al. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation. 2005;79(10):1277-1286.
Hirsch HH, Randhawa P; Practice ASTIDCo. BK virus in solid organ transplant recipients. Am J Transplant. 2009;9(Suppl 4):S136-146.
Lamarche C, Orio J, Collette S, et al. BK polyomavirus and the transplanted kidney: immunopathology and therapeutic approaches. Transplantation. 2016;100(11):2276-2287.
Korth J, Widera M, Dolff S, et al. Impact of low-level BK polyomavirus viremia on intermediate-term renal allograft function. Transpl Infect Dis. 2018;20(1).
Elfadawy N, Flechner SM, Schold JD, et al. Transient versus persistent BK viremia and long-term outcomes after kidney and kidney-pancreas transplantation. Clin J Am Soc Nephrol. 2014;9(3):553-561.
Boan P, Hewison C, Swaminathan R, et al. Optimal use of plasma and urine BK viral loads for screening and predicting BK nephropathy. BMC Infect Dis. 2016;16:342.
Hertz-Tang AL, Astor BC, Mandelbrot DA, Mohamed MA, Djamali A, Parajuli S. BK viremia is not associated with adverse outcomes in the absence of BK nephropathy. Clin Transplant. 2018:e13283.
Mohan S, Palanisamy A, Tsapepas D, et al. Donor-specific antibodies adversely affect kidney allograft outcomes. J Am Soc Nephrol. 2012;23(12):2061-2071.
Willicombe M, Brookes P, Sergeant R, et al. De novo DQ donor-specific antibodies are associated with a significant risk of antibody-mediated rejection and transplant glomerulopathy. Transplantation. 2012;94(2):172-177.
Jorgenson MR, Descourouez JL, Lyu B, et al. Management of BK viremia is associated with a lower risk of subsequent cytomegalovirus infection in kidney transplant recipients. Clin Transplant. 2020;34(3):e13798.
Parajuli S, Joachim E, Alagusundaramoorthy S, et al. Subclinical antibody-mediated rejection after kidney transplantation: treatment outcomes. Transplantation. 2019;103(8):1722-1729.
Parajuli S, Aziz F, Garg N, et al. Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression. World J Transplant. 2019;9(6):123-133.
Hirsch HH, Randhawa PS. BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13528.
Parajuli S, Redfield RR, Astor BC, Djamali A, Kaufman DB, Mandelbrot DA. Outcomes in the highest panel reactive antibody recipients of deceased donor kidneys under the new kidney allocation system. Clin Transplant. 2017;31(3).
Cotiguala L, Masood A, Park JM, Samaniego-Picota MD, Kaul DR, Naik AS. Increasing net immunosuppression after BK polyoma virus infection. Transpl Infect Dis. 2020:e13472.
Mohamed M, Parajuli S, Muth B, et al. In kidney transplant recipients with BK polyomavirus infection, early BK nephropathy, microvascular inflammation, and serum creatinine are risk factors for graft loss. Transpl Infect Dis. 2016;18(3):361-371.
Drachenberg CB, Hirsch HH, Papadimitriou JC, et al. Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation. Transplantation. 2007;84(3):323-330.
Schachtner T, Stein M, Babel N, Reinke P. The loss of BKV-specific immunity from pretransplantation to posttransplantation identifies kidney transplant recipients at increased risk of BKV replication. Am J Transplant. 2015;15(8):2159-2169.
Parajuli S, Astor BC, Kaufman D, et al. Which is more nephrotoxic for kidney transplants: BK nephropathy or rejection? Clin Transplant. 2018;32(4):e13216.
Shenagari M, Monfared A, Eghtedari H, et al. BK virus replication in renal transplant recipients: analysis of potential risk factors may contribute in reactivation. J Clin Virol. 2017;96:7-11.
Hocker B, Schneble L, Murer L, et al. Epidemiology of and risk factors for BK polyomavirus replication and nephropathy in pediatric renal transplant recipients: an international CERTAIN registry study. Transplantation. 2019;103(6):1224-1233.
Demey B, Tinez C, Francois C, et al. Risk factors for BK virus viremia and nephropathy after kidney transplantation: a systematic review. J Clin Virol. 2018;109:6-12.
Malik O, Saleh S, Suleiman B, et al. Prevalence, risk factors, treatment, and overall impact of BK viremia on kidney transplantation. Transplant Proc. 2019;51(6):1801-1809.
Schaub S, Hirsch HH, Dickenmann M, et al. Reducing immunosuppression preserves allograft function in presumptive and definitive polyomavirus-associated nephropathy. Am J Transplant. 2010;10(12):2615-2623.
Pai D, Mann DM, Malik A, Hoover DR, Fyfe B, Mann RA. Risk factors for the development of BK virus nephropathy in renal transplant recipients. Transplant Proc. 2015;47(8):2465-2469.
Drachenberg CB, Papadimitriou JC, Mann D, Hirsch HH, Wali R, Ramos E. Negative impact of human leukocyte antigen matching in the outcome of polyomavirus nephropathy. Transplantation. 2005;80(2):276-278.
Dall A, Hariharan S. BK virus nephritis after renal transplantation. Clin J Am Soc Nephrol. 2008;3(Suppl 2):S68-S75.
Pham PT, Schaenman J, Pham PC. BK virus infection following kidney transplantation: an overview of risk factors, screening strategies, and therapeutic interventions. Curr Opin Organ Transplant. 2014;19(4):401-412.
Garcia Urbán J, Gurrado K, Brea Rivas PC, et al. A case-control study to assess the role of polyomavirus in transplant complications: where do we stand? Transpl Infect Dis. 2020:e13432.
Manzetti J, Weissbach FH, Graf FE, et al. BK polyomavirus evades innate immune sensing by disrupting the mitochondrial network and promotes mitophagy. iScience. 2020;23(7):101257.
Lorentzen EM, Henriksen S, Kaur A, et al. Early fulminant BK polyomavirus-associated nephropathy in two kidney transplant patients with low neutralizing antibody titers receiving allografts from the same donor. Virol J. 2020;17(1):5.
Ahlenstiel-Grunow T, Sester M, Sester U, Hirsch HH, Pape L. BK polyomavirus-specific T cells as a diagnostic and prognostic marker for BK polyomavirus infections after pediatric kidney transplantation. Transplantation. 2020;104(11):2393-2402.
Bae H, Na DH, Chang JY, et al. Usefulness of BK virus-specific interferon-gamma enzyme-linked immunospot assay for predicting the outcome of BK virus infection in kidney transplant recipients. Korean J Intern Med. 2020.
Pello OM, Innes AJ, Bradshaw A, et al. BKV-specific T cells in the treatment of severe refractory haemorrhagic cystitis after HLA-haploidentical haematopoietic cell transplantation. Eur J Haematol. 2017;98(6):632-634.
Jahan S, Scuderi C, Francis L, et al. T-cell adoptive immunotherapy for BK nephropathy in renal transplantation. Transpl Infect Dis. 2020:e13399.
Gabardi S, Pavlakis M, Tan C, et al. New England BK consortium: regional survey of BK screening and management protocols in comparison to published consensus guidelines. Transpl Infect Dis. 2018;20(6):e12985.
Gard L, van Doesum W, Niesters HGM, et al. A delicate balance between rejection and BK polyomavirus associated nephropathy; a retrospective cohort study in renal transplant recipients. PLoS One. 2017;12(6):e0178801.
Chen XT, Li J, Deng RH, et al. The therapeutic effect of switching from tacrolimus to low-dose cyclosporine A in renal transplant recipients with BK virus nephropathy. Biosci Rep. 2019;39(2).
Polanco N, González Monte E, Folgueira MD, et al. Everolimus-based immunosuppression therapy for BK virus nephropathy. Transplant Proc. 2015;47(1):57-61.