To compare everolimus (EVR) plus low-dose tacrolimus (TAC) with mycophenolic acid (MPA) plus standard-dose TAC with regards to rates of cytomegalovirus (CMV) disease in de novo kidney-transplant recipients (KTRs).
This single-center retrospective study included 187 de novo KTRs; 59 patients (31.6%) received EVR/low-dose TAC (group 1); 128 patients (68.4%) received MPA with standard-dose TAC (group 2). All received anti-thymocyte globulins as the induction therapy, and steroid-sparing strategy. Valganciclovir prophylaxis was mandatory for CMV D+/R− KTRs (seronegative recipients of a seropositive donor) in both groups and for R+ seropositive recipients (only in group 2).
The 2-year incidence of CMV disease was low and comparable between groups: 6.8% and 7.0% in groups 1 and 2, respectively (p = 0.94). There was no statistical difference in CMV serostatus (p = 1). However, CMV disease tended to be less frequent, though not statistically different, in R+ KTRs receiving EVR without prophylaxis (3.7% vs. 8.5% in groups 1 and 2, respectively) and in patients without EVR discontinuation (2.6% vs. 6.9% in patients who did not discontinue MPA (p = 0.29). Two-year graft function was good and comparable between groups (median eGFR of 54.2 and 53.0 mL/min in groups 1 and 2, respectively; p = 0.47); incidence of immunological events was low. Significantly more patients in group 1 discontinued EVR because of adverse events than patients that discontinued MPA in group 2 (35.6% in group 1 vs. 10.2% in group 2; p < 0.001).
Everolimus plus low-dose TAC given to de novo KTRs was associated with low rates of CMV disease, especially in R+ patients with no CMV prophylaxis.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
De Keyzer K, Van Laecke S, Peeters P, Vanholder R (2011) Human cytomegalovirus and kidney transplantation: a clinician’s update. Am J Kidney Dis 58:118–126. https://doi.org/10.1053/j.ajkd.2011.04.010
Hodson EM, Jones CA, Webster AC, Strippoli GF, Barclay PG, Kable K, Vimalachandra D, Craig JC (2005) Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials. Lancet 365:2105–2115. https://doi.org/10.1016/S0140-6736(05)66553-1
Humar A, Snydman D, AST Infectious Diseases Community of Practice (2009) Cytomegalovirus in solid organ transplant recipients. Am J Transplant 9(Suppl 4):S78–86. https://doi.org/10.1111/j.1600-6143.2009.02897.x
Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A (2018) TheThirdInternationalConsensusGuidelinesonthemanagementof cytomegalovirusinsolid-organtransplantation. Transplantation 102:900–931. https://doi.org/10.1097/TP.0000000000002191
Fehr T, Cippà PE, Mueller NJ (2015) Cytomegalovirus post kidney transplantation: prophylaxis versus pre-emptive therapy? Transpl Int 28:1351–1356. https://doi.org/10.1111/tri.12629
Humar A, Lebranchu Y, Vincenti F, Blumberg EA, Punch JD, Limaye AP, Abramowicz D, Jardine AG, Voulgari AT, Ives J, Hauser IA, Peeters P (2010) The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Am J Transplant 10:1228–1237. https://doi.org/10.1111/j.1600-6143.2010.03074.x
Arthurs SK, Eid AJ, Pedersen RA, Kremers WK, Cosio FG, Patel R, Razonable RR (2008) Delayed-onset primary cytomegalovirus disease and the risk of allograft failure and mortality after kidney transplantation. Clin Infect Dis 46:840–846. https://doi.org/10.1086/528718
Florescu DF, Qiu F, Schmidt CM, Kalil AC (2014) A direct and indirect comparison meta-analysis on the efficacy of cytomegalovirus preventive strategies in solid organ transplant. Clin Infect Dis 58:785–803. https://doi.org/10.1093/cid/cit945
Tedesco Silva Jr H, Cibrik D, Johnston T, Lackova E, Mange K, Panis C, Walker R, Wang Z, Zibari G, Kim YS (2010) Everolimusplusreduced-exposureCsAversusmycophenolicacidplusstandard- exposureCsAinrenal-transplantrecipients. Am J Transplant 10:1401–1413. https://doi.org/10.1111/j.1600-6143.2010.03129.x
Tedesco-Silva H, Felipe C, Ferreira A, Cristelli M, Oliveira N, Sandes-Freitas T, Aguiar W, Campos E, Gerbase-De Lima M, Franco M, Medina-Pestana J (2015) Reduced incidence of cytomegalovirus infection in kidney transplant recipients receiving everolimus and reduced tacrolimus doses. Am J Transplant 15:2655–2664. https://doi.org/10.1111/ajt.13327
Qazi Y, Shaffer D, Kaplan B, Kim DY, Luan FL, Peddi VR, Shihab F, Tomlanovich S, Yilmaz S, McCague K, Patel D, Mulgaonkar S (2017) Efficacy and safety of everolimus plus low-dose tacrolimus versus mycophenolate mofetil plus standard-dose tacrolimus in de novo renal transplant recipients: 12-month data. Am J Transplant 17:1358–1369. https://doi.org/10.1111/ajt.14090
Pascual J, Berger SP, Witzke O et al (2018) Everolimus with reduced calcineurin inhibitor exposure in renal transplantation. J Am Soc Nephrol 29:1979–1991. https://doi.org/10.1681/ASN.2018010009
Berger SP, Sommerer C, Witzke O et al (2019) Two-year outcomes in de novo renal transplant recipients receiving everolimus—facilitated calcineurin inhibitor reduction regimen from TRANSFORM study. Am J Transplant 19:3018–3034. https://doi.org/10.1111/ajt.15480
Kudchodkar SB, Yu Y, Maguire TG, Alwine JC (2004) Human cytomegalovirus infection induces rapamycin-insensitive phosphorylation of downstream effectors of mTOR kinase. J Virol 78:11030–11039. https://doi.org/10.1128/JVI.78.20.11030-11039.2004
Gerna G, Lilleri D, Chiesa A, Zelini P, Furione M, Comolli G, Pellegrini C, Sarchi E, Migotto C, Bonora MR, Meloni F, Arbustini E (2011) Virologic and immunologic monitoring of cytomegalovirus to guide preemptive therapy in solid-organ transplantation. Am J Transplant 11:2463–2471. https://doi.org/10.1111/j.1600-6143.2011.03636.x
Devresse A, Leruez-Ville M, Scemia A et al (2018) Reduction in late onset cytomegalovirus primary disease after discontinuation of antiviral prophylaxis in kidney transplant recipients treated with de novo everolimus. Transpl Infect Dis 20:e12846. https://doi.org/10.1111/tid.12846
Cristelli MP, Esmeraldo RM, Pinto CM et al (2018) The influence of mTOR inhibitors on the incidence of CMV infection in high-risk donor positive-recipient negative (D+/R-) kidney transplant recipients. Transpl Infect Dis 20:e12907. https://doi.org/10.1111/tid.12907
Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, Pikis A, Razonable RR, Miller V, Griffiths PD (2017) Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum (2017) definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials. Clin Infect Dis 64(1):87–91. https://doi.org/10.1093/cid/ciw668
Basso G, Felipe CR, Cristelli MP et al (2018) The effect of anti-thymocyte globulin and everolimus on the kinetics of cytomegalovirus viral load in seropositive kidney transplant recipients without prophylaxis. Transpl Infect Dis 20:e12919. https://doi.org/10.1111/tid.12919
Brennan DC, Legendre C, Patel D, Mange K, Wiland A, McCague K, Shihab FS (2011) Cytomegalovirus incidence between everolimus versus mycophenolate in de novo renal transplants: pooled analysis of three clinical trials. Am J Transplant 11:2453–2462. https://doi.org/10.1111/j.1600-6143.2011.03674.x
Shihab F, Qazi Y, Mulgaonkar S, McCague K, Patel D, Peddi VR, Shaffer D (2017) Association of clinical events with everolimus exposure in kidney transplant patients receiving low doses of tacrolimus. Am J Transplant 17:2363–2371. https://doi.org/10.1111/ajt.14215
Mithani Z, Gralla J, Adebiyi O, Klem P, Cooper JE, Wiseman AC (2018) De novo donor-specific antibody formation in tacrolimus-based, mycophenolate versus mammalian target of rapamycin immunosuppressive regimens. Exp Clin Transplant 16:23–30. https://doi.org/10.6002/ect.2016.0234
Kurdi A, Martinet W, De Meyer GRY (2018) mTOR inhibition and cardiovascular diseases: dyslipidemia and atherosclerosis. Transplantation 102:S44–S46. https://doi.org/10.1097/TP.0000000000001693
This study was not funded.
Conflict of interest
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Manière, L., Noble, J., Terrec, F. et al. Cytomegalovirus disease in de novo kidney-transplant recipients: comparison of everolimus-based immunosuppression without prophylaxis with mycophenolic acid-based immunosuppression with prophylaxis. Int Urol Nephrol (2020). https://doi.org/10.1007/s11255-020-02676-8
- Kidney transplantation
- Mycophenolic acid