Five-year single-center analysis of cytomegalovirus viremia in kidney transplant recipients and possible implication for novel prophylactic therapy approaches.
antiviral drug resistance
immunosuppression
infection
letermovir
prophylaxis
transplantation
valganciclovir
virus
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:
05 Jan 2024
05 Jan 2024
Historique:
revised:
15
12
2023
received:
31
08
2023
accepted:
19
12
2023
medline:
5
1
2024
pubmed:
5
1
2024
entrez:
5
1
2024
Statut:
aheadofprint
Résumé
Cytomegalovirus (CMV) infections are a common complication after kidney transplantation (KTx) and negatively affecting patient outcome. Valganciclovir (VGC) prophylaxis is often limited by drug-induced side effects and dose reduction due to decline in kidney function. In the present study, episodes of CMV viremia in the first year after KTx in a cohort of 316 recipients were analyzed retrospectively to identify risk factors linked to persistent infections. In the studied cohort, 18.7% of patients showed a high-risk (HR) constellation (D+/R-) for CMV infections. CMV viremia affected 22% of our cohort, with HR patients being the most affected cohort (44.1%). Within this group, most viremic events (65.3%) occurred while patients were still on prophylactic therapy, showing significantly higher viral loads and a longer duration compared to seropositive recipients. The analysis at hand revealed that detection of viremia under ongoing antiviral prophylaxis bears an increased risk for sustained viral replication and antiviral drug resistance in HR patients. We identified low estimated glomerular filtration rate (eGFR) and lower dose VGC prophylaxis post-KTx as a risk factor for breakthrough infections in HR patients in our single center cohort. These patients might benefit from a closer CMV monitoring or novel prophylactic agents as letermovir.
Sections du résumé
BACKGROUND
BACKGROUND
Cytomegalovirus (CMV) infections are a common complication after kidney transplantation (KTx) and negatively affecting patient outcome. Valganciclovir (VGC) prophylaxis is often limited by drug-induced side effects and dose reduction due to decline in kidney function.
METHOD
METHODS
In the present study, episodes of CMV viremia in the first year after KTx in a cohort of 316 recipients were analyzed retrospectively to identify risk factors linked to persistent infections.
RESULTS
RESULTS
In the studied cohort, 18.7% of patients showed a high-risk (HR) constellation (D+/R-) for CMV infections. CMV viremia affected 22% of our cohort, with HR patients being the most affected cohort (44.1%). Within this group, most viremic events (65.3%) occurred while patients were still on prophylactic therapy, showing significantly higher viral loads and a longer duration compared to seropositive recipients.
CONCLUSION
CONCLUSIONS
The analysis at hand revealed that detection of viremia under ongoing antiviral prophylaxis bears an increased risk for sustained viral replication and antiviral drug resistance in HR patients. We identified low estimated glomerular filtration rate (eGFR) and lower dose VGC prophylaxis post-KTx as a risk factor for breakthrough infections in HR patients in our single center cohort. These patients might benefit from a closer CMV monitoring or novel prophylactic agents as letermovir.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14233Informations de copyright
© 2024 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.
Références
Prakash K, Chandorkar A, Saharia KK. Utility of CMV-specific immune monitoring for the management of CMV in solid organ transplant recipients: a clinical update. Diagnostics. 2021;11(5):875.
De Keyzer K, Van Laecke S, Peeters P, Vanholder R. Human cytomegalovirus and kidney transplantation: a clinician's update. Am J Kidney Dis. 2011;58(1):118-126.
Meesing A, Razonable RR. Absolute lymphocyte count thresholds: a simple, readily available tool to predict the risk of cytomegalovirus infection after transplantation. Open Forum Infect Dis. 2018;5(10):ofy230.
Fehr T, Cippà PE, Mueller NJ. Cytomegalovirus post kidney transplantation: prophylaxis versus pre-emptive therapy? Transpl Int. 2015;28(12):1351-1356.
Jehn U, Schütte-Nütgen K, Bautz J, et al. Cytomegalovirus viremia after living and deceased donation in kidney transplantation. J Clin Med. 2020;9(1):252.
Selvey LA, Lim WH, Boan P, et al. Cytomegalovirus viraemia and mortality in renal transplant recipients in the era of antiviral prophylaxis. Lessons from the western Australian experience. BMC Infect Dis. 2017;17(1):501.
Desai R, Collett D, Watson CJE, Johnson PJ, Moss P, Neuberger J. Impact of cytomegalovirus on long-term mortality and cancer risk after organ transplantation. Transplantation. 2015;99(9):1989-1994.
Razonable RR. Drug-resistant cytomegalovirus: clinical implications of specific mutations. Curr Opin Organ Transplant. 2018;23(4):388-394.
Coppock GM, Blumberg E. New treatments for cytomegalovirus in transplant patients. Curr Opin Nephrol Hypertens. 2019;28(6):587-592.
Kotton CN, Kumar D, Caliendo AM, et al. The Third International Consensus Guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2018;102(6):900-931.
Avery RK, Alain S, Alexander BD, et al. Maribavir for refractory cytomegalovirus infections with or without resistance post-transplant: results from a phase 3 randomized clinical trial. Clin Infect Dis. 2021;75(4):690-701.
El Helou G, Lahr B, Razonable R. Absolute lymphocyte count as marker of cytomegalovirus and allograft rejection: is there a “Safe Corridor” after kidney transplantation? Transpl Infect Dis. 2021;23(2):e13489.
Ljungman P, Boeckh M, Hirsch HH, et al. Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials. Clin Infect Dis. 2017;64(1):87-91.
Jorgenson MR, Descourouez JL, Cardinale B, et al. Risk of opportunistic infection in kidney transplant recipients with cytomegalovirus infection and associated outcomes. Transpl Infect Dis. 2019;21(3):e13080.
Smedbråten YV, Sagedal S, Leivestad T, et al. The impact of early cytomegalovirus infection after kidney transplantation on long-term graft and patient survival. Clin Transplant. 2014;28(1):120-126.
Sagedal S, Nordal KP, Hartmann A, et al. The impact of cytomegalovirus infection and disease on rejection episodes in renal allograft recipients. Am J Transplant. 2002;2(9):850-856.
Hasegawa J, Hatakeyama S, Wakai S, et al. Preemptive anti-cytomegalovirus therapy in high-risk (donor-positive, recipient-negative cytomegalovirus serostatus) kidney transplant recipients. Int J Infect Dis. 2017;65:50-56.
Díaz J, Henao J, Rodelo J, García Á, Arbeláez M, Jaimes F. Incidence and risk factors for cytomegalovirus disease in a Colombian cohort of kidney transplant recipients. Transplant Proc. 2014;46(1):160-166.
Cordero E, Casasola C, Ecarma R, Danguilan R. Cytomegalovirus disease in kidney transplant recipients: incidence, clinical profile, and risk factors. Transplant Proc. 2012;44(3):694-700.
Hughes D, Hafferty J, Fulton L, et al. Donor and recipient CMV serostatus and antigenemia after renal transplantation: an analysis of 486 patients. J Clin Virol. 2008;41(2):92-95.
Fernández-Ruiz M, Arias M, Campistol JM, et al. Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice. Transpl Int. 2015;28(9):1042-1054.
Di Cristanziano V, Affeldt P, Trappe M, et al. Combined therapy with intravenous immunoglobulins, letermovir and (val-)ganciclovir in complicated courses of CMV-infection in transplant recipients. Microorganisms. 2021;9(8):1666.
Limaye AP, Budde K, Humar A, et al. Letermovir vs valganciclovir for prophylaxis of cytomegalovirus in high-risk kidney transplant recipients: a randomized clinical trial. JAMA. 2023;330(1):33-42.
Zuhair M, Smit GSA, Wallis G, et al. Estimation of the worldwide seroprevalence of cytomegalovirus: a systematic review and meta-analysis. Rev Med Virol. 2019;29(3):e2034.
Chaudhari I, Leung M, Bateni B. Characterization of cytomegalovirus viremia in renal transplant recipients. Can J Hosp Pharm. 2022;75(1):6-14.
de Matos SB, Meyer R, de Mendonce Lima FW. Cytomegalovirus infection after renal transplantation: occurrence, clinical features, and the cutoff for antigenemia in a University Hospital in Brazil. Infect Chemother. 2017;49(4):255-261.
Hernandez C, Mabilangan C, Burton C, Doucette K, Preiksaitis J. Cytomegalovirus transmission in mismatched solid organ transplant recipients: are factors other than anti-viral prophylaxis at play? Am J Transplant. 2021;21(12):3958-3970.
Khurana MP, Lodding IP, Mocroft A, et al. Risk factors for failure of primary (val)ganciclovir prophylaxis against cytomegalovirus infection and disease in solid organ transplant recipients. Open Forum Infect Dis. 2019;6(6):ofz215.
Nafar M, Roshan A, Pour-Reza-Gholi F, et al. Prevalence and risk factors of recurrent cytomegalovirus infection in kidney transplant recipients. Iran J Kidney Dis. 2014;8(3):231-235.
Lumbreras C, Manuel O, Len O, Ten Berge IJM, Sgarabotto D, Hirsch HH. Cytomegalovirus infection in solid organ transplant recipients. Clin Microbiol Infect. 2014;20(suppl 7):19-26.
Stevens DR, Sawinski D, Blumberg E, Galanakis N, Bloom RD, Trofe-Clark J. Increased risk of breakthrough infection among cytomegalovirus donor-positive/recipient-negative kidney transplant recipients receiving lower-dose valganciclovir prophylaxis. Transplant Infectious Disease. 2015;17(2):163-173.