<scp>C</scp>ytomegalovirus &amp; <scp>E</scp>pstein <scp>B</scp>arr <scp>V</scp>irus serostatus as a predictor of the long‐term outcome of kidney transplantation

Page, Amelia K. Le; Mackie, Fiona; McTaggart, Steven; Kennedy, Seán

doi:10.1111/nep.12149

Cited by 17 publications

(16 citation statements)

References 17 publications

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“…Cytomegalovirus (CMV) is a herpes virus often reported as the most important viral pathogen after kidney transplantation. [1][2][3] It is a major cause of morbidity and mortality, being associated with retinitis, pneumonitis, colitis, encephalitis, allograft damage and allograft loss, among others. [1][2][3][4] CMV syndrome or disease may occur as a consequence of reactivation of latent infections or through primary infection, acquired from the donor or from the environment.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] It is a major cause of morbidity and mortality, being associated with retinitis, pneumonitis, colitis, encephalitis, allograft damage and allograft loss, among others. [1][2][3][4] CMV syndrome or disease may occur as a consequence of reactivation of latent infections or through primary infection, acquired from the donor or from the environment. 2 The major risk factor for CMV syndrome or disease is the pretransplantation serostatus: CMV seronegative transplant recipients with a seropositive donor (D + R -) have the highest risk, while seropositive recipients (R + ) have an intermediate risk and seronegative recipients with seronegative donors (D -R -) have the lowest risk.…”

Section: Introductionmentioning

confidence: 99%

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Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

Blázquez-Navarro

Dang-Heine

Bauer

et al. 2019

Preprint

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Post-transplantation cytomegalovirus (CMV) syndrome can be prevented using the antiviral drug (val)ganciclovir. (Val)ganciclovir is typically administered following a prophylactic or a pre-emptive strategy. The prophylactic strategy entails early universal administration, the pre-emptive strategy, early treatment in case of infection. However, it is not clear which strategy is superior with respect to transplantation outcome; sex-specific effects of these prevention strategies are not known. We have retrospectively analysed 540 patients from the multi-centre Harmony study along eight pre-defined visits: 308 were treated according to a prophylactic, 232 according to a pre-emptive strategy. As expected, we observed an association of prophylactic strategy with lower incidence of CMV syndrome, delayed onset and lower viral loads compared to the pre-emptive strategy. However, in female patients, the prophylactic strategy was associated with a strong impairment of glomerular filtration rate one year post-transplant (difference: -12.0±4.2 mL·min -1 ·1.73m -2 , P=0.005). Additionally, we observed a tendency of higher incidence of acute rejection and severe BK virus reactivation in the prophylactic strategy group. While the prophylactic strategy was more effective for preventing CMV syndrome, our results suggest for the first time that the prophylactic strategy might lead to inferior transplantation outcomes in female patients, providing evidence for a strong association with sex.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

Blázquez-Navarro

Dang-Heine

Bauer

et al. 2019

Preprint

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“…When analyzing the serostatus, the median age of kidney transplant recipients being seropositive for cytomegalovirus and Epstein-Barr virus disease is significantly higher. 15 Taken together, the prevalence of seropositivity is increasing with age while the rate of active viral infection is decreasing. However, active viral infections in older patients are associated with inferior outcomes.…”

Section: Introductionmentioning

confidence: 99%

A Rationale for Age-Adapted Immunosuppression in Organ Transplantation

et al. 2015

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Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of transplant recipients are currently older >50 years and organs from elderly donors are more frequently utilized. Nevertheless, the benefit of transplantation in older patients is well recognized whereas the most frequent causes of death among older recipients are potentially linked to side effects of their immunosuppressants. Immunosenescence is a physiological part of aging linked to higher rates of diabetes, bacterial infections and malignancies representing the major causes of death in older patients. These age-related changes impact older transplant candidates and may have significant implications for an age-adapted immunosuppression. For instance, immunosenescence is linked to lower rates of acute rejections in older recipients while the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus following transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors and mTOR inhibitors. This review presents current knowledge for an age-adapted immunosuppression based on both, experimental and clinical studies in and beyond transplantation. Recommendations of maintenance and induction therapy may help to improve graft function and to design future clinical trials in the elderly.

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“…Morbidity and mortality were high until the development of effective antiviral agents and widespread implementation of serologic risk stratification, valganciclovir prophylaxis, and preemptive monitoring . These measures have significantly reduced the burden of disease and largely equalized the mortality differences across the four CMV donor/recipient serogroups in many but not all studies . However, post‐prophylaxis (late‐onset) CMV reactivation still occurs, contributing to graft loss and premature death via its direct and indirect effects .…”

Section: Introductionmentioning

confidence: 99%

The impact of recurrent cytomegalovirus infection on long‐term survival in solid organ transplant recipients

Gardiner

Chow

Brilleman

et al. 2019

Transplant Infectious Dis

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Background: Cytomegalovirus (CMV) remains a significant contributor to morbidity and mortality following solid organ transplantation (SOT). While recurrent infection occurs in up to 30% of patients, its impact on mortality is unclear. The aim of this study was to explore the relationship between recurrent CMV infection and longterm survival in SOT recipients. Methods:We performed a retrospective cohort study of SOT recipients who completed treatment for an episode of CMV infection. Patients were followed until death, loss to follow-up or 10 years following CMV treatment completion. Univariable and multivariable hazard ratios (HR) were calculated, treating relapse and rejection following CMV as time-varying. Results: About 79 kidney, 52 heart, 34 liver, and 5 liver-kidney transplant recipients were included. About 62/170 died, at a median of 3.8 years (IQR 0.8-6.6 years). Median follow-up among the 108 survivors was 7.4 years (IQR 3.7-10 years). Recurrent CMV infection occurred in 49/170 (29%), 67% within 6 months of treatment completion.Mortality among those who relapsed was 39% (19/49) vs 36% (43/121) in those who remained relapse-free (unadjusted HR 1.59, 95% CI 0.92-2.75, P = .10). After adjusting for age and transplanted organ, findings were similar (HR 1.68, 95% CI 0.93-3.04, P = .09). Conclusions: Mortality following CMV remains high even in the valganciclovir era.Although our findings suggest a possible increased risk of death among patients with recurrent CMV, these did not reach statistical significance. The complex nature of these patients, multiple potential confounders, and limited statistical power made detection of small effects difficult. Larger prospective studies evaluating the clinical impact of strategies to reduce recurrence are needed. K E Y W O R D S recurrent cytomegalovirus, survival, transplant S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Gardiner BJ, Chow JK, Brilleman SL, Peleg AY, Snydman DR. The impact of recurrent cytomegalovirus infection on long-term survival in solid organ transplant recipients. Transpl Infect Dis.

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Cytomegalovirus & Epstein Barr Virus serostatus as a predictor of the long‐term outcome of kidney transplantation

Abstract: We conclude that in the current era of viral prophylaxis and surveillance, long-term outcome for the kidney transplant population is unaffected by D/R CMV and EBV serostatus.

Cited by 17 publications

References 17 publications

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

A Rationale for Age-Adapted Immunosuppression in Organ Transplantation

The impact of recurrent cytomegalovirus infection on long‐term survival in solid organ transplant recipients

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