OPTN/SRTR 2021 Annual Data Report: Kidney

Lentine, Krista L.; Smith, Jodi M.; Miller, Jonathan; Bradbrook, K.; Larkin, Lindsay; Weiss, Samantha; Handarova, Dzhuliyana K.; Temple, Kayla J.; Israni, Ajay K.; Snyder, Jon J.

doi:10.1016/j.ajt.2023.02.004

Cited by 85 publications

(76 citation statements)

References 3 publications

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“…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 . Third, myelotoxicity was evaluated as leukopenia or neutropenia, although valganciclovir may also cause anemia and thrombocytopenia.…”

Section: Discussionmentioning

confidence: 99%

“…Cytomegalovirus (CMV) disease is a major cause of morbidity and mortality among kidney transplant recipients. The incidence is highest in the subgroup of CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor, who comprise approximately 20% of all kidney transplant recipients . Oral valganciclovir, 900 mg, daily for 200 days after transplant is the current standard of care for prophylaxis of CMV disease among CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor .…”

Section: Introductionmentioning

confidence: 99%

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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: 99%

Section: Introductionmentioning

confidence: 99%

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

Limaye

Budde

Humar

et al. 2023

JAMA

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“…Overall, we recommend a cautious interpretation of data that takes into consideration accuracy of national database studies, which is excellent for graft and patient survival, but may suffer from less detail regarding other covariates like rejection, infections, and malignancies. Rejection has been overall decreasing in incidence among all patient populations and its association with survival is variable [63]. As such, focusing on strong outcomes and less on rejection data when making recommendations for immunosuppression is advisable.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppression in HIV-positive kidney transplant recipients

Sorohan

Ismail

Leca

2023

Current Opinion in Organ Transplantation

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Purpose of study The purpose of this review is to provide the current state of immunosuppression therapy in kidney transplant recipients (KTR) with HIV and to discuss practical dilemmas to better understand and manage these patients. Recent findings Certain studies find higher rates of rejection, which raises the need to critically assess the approach to immunosuppression management in HIV-positive KTR. Induction immunosuppression is guided by transplant center-level preference rather than by the individual patient characteristics. Earlier recommendations expressed concerns about the use of induction immunosuppression, especially utilizing lymphocyte-depleting agents; however, updated guidelines based on newer data recommend that induction can be used in HIV-positive KTR, and the choice of agent be made according to immunological risk. Likewise, most studies point out success with using first-line maintenance immunosuppression including tacrolimus, mycophenolate, and steroids. In selected patients, belatacept appears to be a promising alternative to calcineurin inhibitors with some well established advantages. Early discontinuation of steroids in this population carries a high risk of rejection and should be avoided. Summary Immunosuppression management in HIV-positive KTR is complex and challenging, mainly because of the difficulty of maintaining a proper balance between rejection and infection. Interpretation and understanding of the current data towards a personalized approach of immunosuppression could improve management in HIV-positive KTR.

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“…In HT, compared with other solid organ transplants, these technologies have more robust application and clinical data for their use, given that the incidence of rejection in other transplanted organs is substantially lower (≈5% to 9% for renal transplantation compared with 13% to 24% for HT at 1 year) 1,2,94 ; biomarkers of end-organ function (creatinine and aspartate aminotransferase/alanine aminotransferase) are reasonable markers of rejection; and biopsies are primarily performed for cause rather than for surveillance, as in HT. As molecular evaluation methodologies continue to develop, the lessons learned from HT will have implications for other solid organ transplant populations.…”

Section: Comparison With Other Solid Organ Transplantsmentioning

confidence: 99%

Selection and Interpretation of Molecular Diagnostics in Heart Transplantation

Goldberg,

Truby,

Agbor-Enoh

et al. 2023

Circulation

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The number of heart transplants performed annually in the United States and worldwide continues to increase, but there has been little change in graft longevity and patient survival over the past 2 decades. The reference standard for diagnosis of acute cellular and antibody-mediated rejection includes histologic and immunofluorescence evaluation of endomyocardial biopsy samples, despite invasiveness and high interrater variability for grading histologic rejection. Circulating biomarkers and molecular diagnostics have shown substantial predictive value in rejection monitoring, and emerging data support their use in diagnosing other posttransplant complications. The use of genomic (cell-free DNA), transcriptomic (mRNA and microRNA profiling), and proteomic (protein expression quantitation) methodologies in diagnosis of these posttransplant outcomes has been evaluated with varying levels of evidence. In parallel, growing knowledge about the genetically mediated immune response leading to rejection (immunogenetics) has enhanced understanding of antibody-mediated rejection, associated graft dysfunction, and death. Antibodies to donor human leukocyte antigens and the technology available to evaluate these antibodies continues to evolve. This review aims to provide an overview of biomarker and immunologic tests used to diagnose posttransplant complications. This includes a discussion of pediatric heart transplantation and the disparate rates of rejection and death experienced by Black patients receiving a heart transplant. This review describes diagnostic modalities that are available and used after transplant and the landscape of future investigations needed to enhance patient outcomes after heart transplantation.

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OPTN/SRTR 2021 Annual Data Report: Kidney

Cited by 85 publications

References 3 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

Immunosuppression in HIV-positive kidney transplant recipients

Selection and Interpretation of Molecular Diagnostics in Heart Transplantation

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