Risk factors for cytomegalovirus infection and disease after kidney transplantation: A meta-analysis

Tang, Yan; Guo, Jiayu; Li, Jie; Zhou, Jiangqiao; Mao, Xiaolan; Qiu, Tao

doi:10.1016/j.trim.2022.101677

Cited by 21 publications

(22 citation statements)

References 48 publications

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“…This study has limitations. First, most participants were White men, but there is no known increased risk for CMV disease conferred by sex or race or ethnicity . Second, the proportion of participants who received lymphocyte-depleting induction immunosuppression, which increases the risk for CMV infection or disease, was lower in the study population than reported in US registry data .…”

Section: Discussionmentioning

confidence: 81%

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients

Limaye

Budde

Humar

et al. 2023

JAMA

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ImportanceValganciclovir for 200 days is standard care for cytomegalovirus (CMV) prophylaxis in high-risk CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor, but its use is limited by myelosuppression.ObjectiveTo compare the efficacy and safety of letermovir with valganciclovir for prevention of CMV disease in CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor.Design, Setting, and ParticipantsRandomized, double-masked, double-dummy, noninferiority, phase 3 trial in adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor at 94 participating sites between May 2018 and April 2021 (final follow-up in April 2022).InterventionsParticipants were randomized in a 1:1 ratio (stratified by receipt of lymphocyte-depleting induction immunosuppression) to receive letermovir, 480 mg, orally daily (with acyclovir) or valganciclovir, 900 mg, orally daily (adjusted for kidney function) for up to 200 days after transplant, with matching placebos.Main Outcomes and MeasuresThe primary outcome was CMV disease, confirmed by an independent masked adjudication committee, through posttransplant week 52 (prespecified noninferiority margin, 10%). CMV disease through week 28 and time to onset of CMV disease through week 52 were secondary outcomes. Exploratory outcomes included quantifiable CMV DNAemia and resistance. The rate of leukopenia or neutropenia through week 28 was a prespecified safety outcome.ResultsAmong 601 participants randomized, 589 received at least 1 dose of the study drug (mean age, 49.6 years; 422 [71.6%] men). Letermovir (n = 289) was noninferior to valganciclovir (n = 297) for prevention of CMV disease through week 52 (10.4% vs 11.8% of participants with committee-confirmed CMV disease; stratum-adjusted difference −1.4% [95% CI, −6.5% to 3.8%]). No participants who received letermovir vs 5 participants (1.7%) who received valganciclovir developed CMV disease through week 28. Time to onset of CMV disease was comparable between the groups (hazard ratio, 0.90 [95% CI, 0.56-1.47]). Quantifiable CMV DNAemia was detected in 2.1% of participants in the letermovir group vs 8.8% in the valganciclovir group by week 28. Of participants evaluated for suspected CMV disease or CMV DNAemia, none (0/52) who received letermovir and 12.1% (8/66) who received valganciclovir had resistance-associated substitutions. The rate of leukopenia or neutropenia through week 28 was lower with letermovir vs valganciclovir (26% vs 64%; difference, −37.9% [95% CI, −45.1% to −30.3%]; P &lt; .001). Fewer participants in the letermovir group than the valganciclovir group discontinued prophylaxis due to adverse events (4.1% vs 13.5%) or drug-related adverse events (2.7% vs 8.8%).Conclusion and RelevanceAmong adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor, letermovir was noninferior to valganciclovir for prophylaxis of CMV disease over 52 weeks, with lower rates of leukopenia or neutropenia, supporting its use for this indication.Trial RegistrationClinicalTrials.gov Identifier: NCT03443869; EudraCT: 2017-001055-30

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Section: Discussionmentioning

confidence: 81%

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients

Limaye

Budde

Humar

et al. 2023

JAMA

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“…Despite prevention strategies that are now currently used after transplantation and that decrease the risk of CMV disease [ 3 ], CMV disease can still occur in up to 50% of high-risk solid-organ transplant (SOT) patients (CMV-seropositive donor/CMV-seronegative recipients, D+/R−) and 17% of CMV-seropositive recipients (R+) [ 4 ]. In a recent meta-analysis, several risk factors for CMV infection or disease were identified: D+/R− serological status, seropositive recipients, use of polyclonal antibodies for induction and/or mycophenolic acid and/or steroids, donors’ and recipients’ advanced age, and history of acute rejection [ 5 ]. In a nationwide retrospective French study, it has been shown that, despite preventive strategies, CMV infection after SOT is associated with an increased risk of acute rejection and graft failure, a higher mortality, and increased costs related to a higher number of inpatient days, number of hospital readmissions, and hospital costs [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

New Insights on CMV Management in Solid Organ Transplant Patients: Prevention, Treatment, and Management of Resistant/Refractory Disease

Kotton

Kamar

2022

Infect Dis Ther

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Cytomegalovirus (CMV) infection can have both direct and indirect effects after solid-organ transplantation, with a significant impact on transplant outcomes. Prevention strategies decrease the risk of CMV disease, although CMV still occurs in up to 50% of high-risk patients. Ganciclovir (GCV) and valganciclovir (VGCV) are the main drugs currently used for preventing and treating CMV. Emerging data suggest that letermovir is as effective as VGCV with fewer hematological side effects. Refractory and resistant CMV also still occur in solid-organ-transplant patients. Maribavir has been shown to be effective and have less toxicity in the treatment of refractory and resistant CMV. In this review paper, we discuss prevention strategies, refractory and resistant CMV, and drug-related side effects and their impact, as well as optimal use of novel anti-CMV therapies.

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“…Donor risk factors previously described include older donor age, and prolonged cold ischemia time, although there is some heterogenicity in the literature 21–23 . A meta‐analysis published in 2022 of risk factors for CMV infection after kidney transplantation found that the use of post‐surgical ATG increases the risk of CMV infection after kidney transplantation by 2.76 times, D+/R‐ increases the risk 2.97 times, postoperative recipient age increases the risk 1.96 times, lymphocytopenia increases the risk 3.26 times, and mycophenolate increases the risk 3.22 times 6 . A retrospective analysis found older recipient age as well as older donor age to be risk factors 24 .…”

Section: Discussionmentioning

confidence: 99%

“…16,20 Therefore, it is important to identify times, lymphocytopenia increases the risk 3.26 times, and mycophenolate increases the risk 3.22 times. 6 A retrospective analysis found older recipient age as well as older donor age to be risk factors. 24 The findings from our risk factor analysis based on kidney pairs validate these findings and build upon previous literature.…”

Section: Discussionmentioning

confidence: 99%

“…While the availability of ganciclovir and its oral prodrug valganciclovir has improved treatment or prevention, CMV infection continues to negatively affect outcomes 3 . It has been associated with infection‐related morbidity and mortality, 2,3 as well as increased risk of acute rejection 4 and graft failure, 5 lower estimated glomerular filtration rate (eGFR), 6 and increased post‐transplant serum creatinine, 7 and increased all‐cause hospital readmissions 8 . Major risk factors include the intensity of immunosuppression and primary infection in seronegative recipients of seropositive grafts (D+/R‐) 9,10 …”

Section: Introductionmentioning

confidence: 99%

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Discordance in cytomegalovirus viremia in kidney recipients from the same donor is associated with the worst outcomes

Zona

Jorgenson

Dolma

et al. 2023

Clinical Transplantation

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Background Cytomegalovirus (CMV) is a common viral infection in kidney transplant recipients (KTR) that has been associated with negative outcomes. The effect on outcomes of concordance versus discordance in CMV between two different recipients of kidneys from the same donor is largely unknown. Methods We reviewed all adult deceased donor kidney transplant recipients (DDKTs) for which both kidneys were transplanted to two different recipients at our center between 2014 and 2019. Recipient pairs from each donor were divided into groups based on concordance or discordance for the development of CMV viremia between the pair; concordant no CMV (cc‐no‐CMV) if neither KTR developed CMV, concordant CMV (cc‐CMV) if both KTRs developed CMV. The discordant group was then further divided based on the individual development of CMV (dc‐CMV) or lack of development of CMV (dc‐no‐CMV). Patient mortality and death‐censored graft failure (DCGF) were outcomes of interest. Results Of 578 KTRs, 67% were cc‐no‐CMV, 5% were cc‐CMV, 14% were dc‐no‐CMV, and 14% dc‐CMV. Some of the baseline characteristics differ among the groups including a higher prevalence of high‐risk serostatus (D+/R‐) in cc‐CMV (32%) and dc‐CMV (32%). In multivariate analysis, with reference to cc‐no‐CMV, dc‐CMV was associated with increased risk for DCGF (HR 3.13, 95% CI 1.58–6.19), and so was delayed graft function. Factors associated with increased risk of mortality were advanced recipient age and DGF. cc‐CMV was neither associated with mortality nor DCGF. Conclusions These findings support that in certain contexts, CMV viremia has adverse allograft outcomes, and this is highlighted when illustrated via discordance in CMV between pair kidneys from the same deceased donor.

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Risk factors for cytomegalovirus infection and disease after kidney transplantation: A meta-analysis

Cited by 21 publications

References 48 publications

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients

New Insights on CMV Management in Solid Organ Transplant Patients: Prevention, Treatment, and Management of Resistant/Refractory Disease

Discordance in cytomegalovirus viremia in kidney recipients from the same donor is associated with the worst outcomes

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