Incidence and risk factors associated with cytomegalovirus infection after the treatment of acute rejection during the first year in kidney transplant recipients receiving preemptive therapy

Abstract

There have been progressive and considerable improvements in the early management of kidney transplant recipients, including HLA matching, induction, maintenance immunosuppressive therapy, and infection prophylaxis, leading to lower incidences of acute rejection and infection, primarily, cytomegalovirus (CMV) infection. 1 The availability of a highly effective oral drug, valganciclovir, is perhaps the primary reason for the growing shift from preemptive therapy to universal CMV prophylaxis. 2 Yet, drug-related toxicities, late CMV infection after discontinuation of prophylaxis, and costs are critical concerns. 3 The intricate relationship between CMV infection and acute rejection, 4,5 as well as their negative influence on renal function and graft survival 6 are well known. A recent retrospective cohort study showed no difference in the incidence of CMV Abstract Introduction: The complex interaction between cytomegalovirus (CMV) infection and acute rejection after kidney transplantation is well recognized.Methods: This single center retrospective cohort analysis investigated the incidence and risk factors associated with CMV infection after treatment for acute rejection (tAR) in kidney transplant recipients receiving only CMV preemptive therapy. Of the 938 kidney transplants performed between 04/30/2014 and 04/30/2015 we identified 87 (9.3%) that were treated for acute rejection within the first year.Results: Most patients (64%) received rATG induction therapy followed by tacrolimus in combination with azathioprine (67%) or mycophenolate (33%) and corticosteroids.The incidence of CMV infection/disease after tAR was 47%, of which 73% occurred within 30 days. Using multivariable logistic regression analysis, eGFR at 1 month (OR = 0.98; 95% CI, 0.97-0.99; P = 0.007) and timing of tAR (OR = 0.98; 95% CI, 0.96-0.99; P = 0.021) were independently associated with CMV infection/disease after tAR. Conclusion:In this cohort of kidney transplant recipients receiving tacrolimus-based immunosuppressive and preemptive CMV therapy, almost 50% developed CMV infection/disease after tARin the first year of transplantation. Early rejection and poor initial renal function were risk factors associated with CMV infection or disease. K E Y W O R D Sacute rejection, cytomegalovirus, kidney transplant

Cytomegalovirus Viremia after Living and Deceased Donation in Kidney Transplantation

“…In line with this, weaker immunosuppression with cyclosporine A or m-TOR instead of tacrolimus was associated with less CMV infections. The role of immunosuppression was emphasized by Felipe et al, who even observed that previous acute rejection episodes were the major risk factor for CMV infection in the first year after transplantation [26]. Notably, we made both observations as in 60.4% of the cases CMV viremia occurred after rejection, whereas in 39.6% of patients, CMV viremia occurred before rejection.…”

Decreased incidence of acute rejection without increased incidence of cytomegalovirus (CMV) infection in kidney transplant recipients receiving rabbit anti‐thymocyte globulin without CMV prophylaxis – a cohort single‐center study

“…There were no differences in the incidence of CMV infection/disease in patients receiving preemptive therapy, both in the CMV D+/R− high‐risk group and after treatment for AR. In one previous cohort analysis, we showed that 47% of patients treated for acute rejection during the first year after transplantation developed CMV infection/disease [10]. The significant reduction in the incidence of acute rejection in patients receiving rATG induction is therefore associated with lower incidence of CMV infection/disease.…”

“…The other patients were monitored at the physician discretion. This targeted strategy was based on the low incidence of CMV disease in this patients receiving AZA [9] but higher incidence after treatment of AR [10]. The preemptive therapy consisted of every other week monitoring the viral replication from the third week after transplantation until the end of the third month, using the CMV pp65 antigenemia assay.…”

“…In this group of patients, the use of induction therapy with basiliximab [6,7] or substitution of azathioprine by mycophenolate [8] may not provide substantial efficacy, safety and cost advantage. In two independent cohorts of patients receiving TAC, AZA, and PRED without induction therapy, we recently showed that the incidence of AR was 32% and of CMV infection was 30% [9], and that the incidence of CMV infection after treatment of AR was 47% [10].…”

Cytomegalovirus in renal transplant recipients from living donors with and without valganciclovir prophylaxis and with immunosuppression based on anti-thymocyte globulin or basiliximab

“…Cytomegalovirus (CMV) is a common complication in solid organ transplant recipients, and it can present as a primary infection, secondary infection, or be reactivate from a latent reserve (Koval 2018). In renal transplant recipients (RTR), the incidence of CMV infection or CMV disease (CMVI/CMVD) varies from 17.8%-63.2% (Helantera et al 2014;Chiasakul et al 2015;Corona-Nakamura et al 2009;de Matos et al, 2017;Felipe et al 2019;Ricart et al 2005;Henrique Pinto et al 2016;Minz et al 2020), and its presence is associated with a reduction in glomerular filtration rate (GFR), acute or chronic rejection (AR), opportunistic infection, high cardiovascular risk, and decrease in survival of the graft and the patient (Viot et al 2015;Courivaud et al 2013;Meijers et al 2015;Hodson et al 2013;Stern et al 2014). The following have all been documented as risk factors for CMV: serology test: IgG-positive donor (D) and IgG-negative recipient (D+/R-); anti-rejection therapy; female sex; advanced age; recipients from a deceased donor; transfusions; HLA-B44; absence and/or short lengths of antiviral prophylaxis treatment; and the use of prednisone (PDN), mycophenolate mofetil (MMF), tacrolimus (TAC), belatacept, or anti-thymocyte globulin (ATG) (Felipe et al 2019;Meije et al 2014;Viot et al 2015;ter Meulen et al, 2000;Wagner et al 2015;Futohi et al 2015;Ricart et al 2005;Bataille et al 2010;Chiasakul et al 2015;Diaz et al 2014;Kotton et al 2018;Abou-Ayache et al 2008;Brennan et al 1997;Humar et al 2010;Razonable et al 2001;Lucia et al 2014;Nafar et al 2014;Vacher-Coponat et al 2006;…”