Cytomegalovirus infection after acute rejection therapy in seropositive kidney transplant recipients

Lee, Y.-M.; Kim, Y.H.; Han, Duck‐Jong; Park, S.-K.; Park, J.S.; Sung, Heungsup; Hong, Hyo-Lim; Kim, T.; Kim, S.-H.; Choi, Sang‐Ho; Woo, Jun Hee; Lee, S.-O.

doi:10.1111/tid.12227

Cited by 20 publications

(21 citation statements)

References 18 publications

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“…This result was confirmed based on a previous study which showed 48% of CMV infection/disease after treatment of acute rejection in another cohort of 144 kidney transplant recipients . Another study showed a relationship between tissue invasive CMV disease and acute rejection (OR 2.81; 95% CI, 1.08‐7.29, P = 0.03) within 6 months of kidney transplantation …”

Section: Discussionsupporting

confidence: 72%

“…A recent retrospective cohort study showed no difference in the incidence of CMV infection in seropositive kidney transplant patients with (n = 75) or without (n = 917) acute rejection, managed with preemptive therapy. But higher incidences of tissue‐invasive disease were observed after acute rejection treatment . Nevertheless, there are not sufficiently robust data or consensus regarding CMV preventive strategies after the treatment of acute rejection .…”

Section: Introductionmentioning

confidence: 99%

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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

Felipe

Ferreira

Paula

et al. 2019

Transplant Infectious Dis

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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

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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

Felipe

Ferreira

Paula

et al. 2019

Transplant Infectious Dis

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“…Furthermore, induction therapies with either depletion of T cells [11] or B cells [12] have been shown to increase the incidence of CMV infection. The same is true after the treatment of acute rejection [13].…”

Section: Risk Factors For CMV Diseasementioning

confidence: 77%

Cytomegalovirus post kidney transplantation: prophylaxis versus pre-emptive therapy?

2015

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SummaryCytomegalovirus is the most important pathogen causing opportunistic infections in kidney allograft recipients. The occurrence of CMV disease is associated with higher morbidity, higher incidence of other opportunistic infections, allograft loss and death. Therefore, an efficient strategy to prevent CMV disease after kidney transplantation is required. Two options are currently available: pre-emptive therapy based on regular CMV PCR monitoring and generalized antiviral prophylaxis during a defined period. In this review, we describe those two approaches, highlight the distinct advantages and risks of each strategy and summarize the four randomized controlled trials performed in this field so far. Taken this evidence together, pre-emptive therapy and anti-CMV prophylaxis are both equally potent in preventing CMV-associated complications; however, the pre-emptive approach may have distinct advantages in allowing for development of long-term anti-CMV immunity. We propose a risk-adapted use of these approaches based on serostatus, immunosuppressive therapy and availability of resources at a particular transplant centre. Cytomegalovirus in kidney transplantationGeneral introduction Cytomegalovirus (CMV) is the most important viral pathogen and the most prevalent opportunistic infection after kidney transplantation [1]. Infection occurs by three ways (in order of incidence): (i) endogenous reactivation of CMV in the recipient, (ii) donor-derived infection transmitted by the allograft and (iii) de novo infection acquired from the general population. From a clinical point of view, three distinctive presentations can occur: asymptomatic viraemia, CMV viral syndrome (with fever, malaise and leukopenia) and CMV tissue invasive disease (with documented end-organ damage in histology or imaging such as colitis, hepatitis, pneumonitis or retinitis).Apart from CMV viral syndrome and tissue invasive disease, a number of indirect immunomodulatory effects of CMV have been postulated [2], thereby increasing the incidence of acute and chronic rejection after solid organ transplantation on one side (probably via a bystander activation of alloreactive T cells during an antiviral response of the host), but also the incidence of other opportunistic infections on the other side. Immunity against CMVThe incidence of CMV infection and serious clinical complications is highly dependent on the serostatus (presence of CMV-specific antibodies) of recipient (R) and donor (D) with the constellation D+RÀ bearing the highest risk, followed by D+R+, DÀR+ and DÀRÀ. Studies on anti-CMV strategies usually distinguish between these risk categories, thereby often summarizing the D+R+ and DÀR+ groups in an intermediate-risk category [3]. The DÀRÀ recipients as ©

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“…The treatment of acute rejection is considered a risk factor for the development of CMV infection, prompting the use of preemptive therapy . Interestingly, in this cohort of patients, no episodes of CMV infection were observed among patients treated for AR who remained on EVR.…”

Section: Discussionmentioning

confidence: 75%

Use of mTOR inhibitor as prophylaxis for cytomegalovirus disease after kidney transplantation: A natural experiment

Cristelli

Felipe

Prizmic

et al. 2019

Clinical Transplantation

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Objectives To describe the incidence of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving an mTOR‐inhibitor‐containing immunosuppressive regimen without prophylactic CMV treatment. Methods This single‐center retrospective cohort analysis included all de novo kidney transplant recipients (09/15/2015‐07/31/2017) receiving 3 mg/kg single dose of rabbit antithymocyte globulin induction, tacrolimus, everolimus, and prednisone. Preemptive therapy was initiated only in patients deemed at higher risk for CMV infection: (a) D+/R− CMV patients; (b) after treatment for acute rejection (ARt); and (c) after everolimus discontinuation (EVRd). Results Of 230 patients, there were no episodes of CMV disease among 217 (94%) without criteria to initiate preemptive therapy. Of 77 (33.5%) patients initiating preemptive therapy, 13 were D+/R−, 30 were ARt, and 34 were EVRd. The overall incidence of first CMV infection/disease was 6% (46.1% in D+/R−, 13.3% ARt [all patients had also discontinued everolimus], and 11.8% after early [<90 days] EVRd). The incidence of biopsy‐proven acute rejection was 5.6%, and median glomerular filtration rate at month 12 was 47 mL/min/1.73m2. One‐year patient and death‐censored graft survivals were 97.4% and 98.1%. Conclusion This study suggests that everolimus‐containing immunosuppressive regimen reduces the need for preventive strategies for CMV infection in the majority of kidney transplant recipients, reducing antiviral drug‐associated toxicities and healthcare‐related expenditures.

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Cytomegalovirus infection after acute rejection therapy in seropositive kidney transplant recipients

Abstract: A high index of suspicion and active evaluation for tissue-invasive CMV disease in KT recipients suffering AR may be necessary to ensure appropriate treatment.

Cited by 20 publications

References 18 publications

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

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

Cytomegalovirus post kidney transplantation: prophylaxis versus pre-emptive therapy?

Use of mTOR inhibitor as prophylaxis for cytomegalovirus disease after kidney transplantation: A natural experiment

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