Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients

Hahn, Deirdré; Hodson, Elisabeth M; Hamiwka, Lorraine; Lee, Vincent; Chapman, Jeremy R.; Craig, Jonathan C.; Webster, Angela C

doi:10.1002/14651858.cd004290.pub3

Cited by 31 publications

(37 citation statements)

References 257 publications

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“…However, mTORi use in kidney transplantation is associated with inferior graft survival 14 , 15 and increased mortality risk 16 , 17 . In recent meta-analysis, Wolf S. et al found that initiation of mTORi within 3 months of kidney transplantation may reduce the future risk of malignancy 18 but in Hahn et al analysis, mTORi treatment failed to demonstrate a reduction in cancer risk 19 . These controversial results regarding the role of mTORi and timing of introduction in transplant outcomes need further evidence for verification.…”

Section: Introductionmentioning

confidence: 99%

Timing of mTORI usage and outcomes in kidney transplant recipients

Lim¹,

Kung²,

Kuo³

et al. 2021

Int. J. Med. Sci.

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The introduction of mammalian target of rapamycin inhibitors (mTORi) as immunosuppressive agents has changed the landscape of calcineurin inhibitor-based immunosuppressive regimens. However, the timing of mTORi conversion and its associated outcomes in kidney transplantation have conflicting results. This study investigated the effect of early or late mTORi post-transplant initiation on major transplant outcomes, including post-transplant malignancy, in kidney transplant recipients in our center. We enrolled 201 kidney transplant recipients with surviving function grafts of >3 months between 1983 and 2016. Patients were divided into three groups: early mTORi (initiated within 6 months of kidney transplantation), late mTORi, (mTORi initiation >6 months after kidney transplantation) and no mTORi. The mean creatinine at conversion was 1.46 ± 0.48 mg/dL and 1.30 ± 0.53 mg/dL for the early and late mTORi groups, respectively. During the study period, 10.5% of mTORi users and 19.2% of mTORi nonusers developed malignancy, mainly urothelial carcinoma. After adjustment for confounding factors, mTORi users were found to have a lower incidence of post-transplant malignancy than did nonusers (adjusted OR: 0.28, P = 0.04). No significant difference was observed between early and late mTORi users. Our results verified the potential advantages of mTORi usage in reducing cancer incidence after kidney transplantation. However, no significant result was found related to the timing of mTORi introduction. Future studies should include a longer observation period with a larger cohort.

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Section: Introductionmentioning

confidence: 99%

Timing of mTORI usage and outcomes in kidney transplant recipients

Lim¹,

Kung²,

Kuo³

et al. 2021

Int. J. Med. Sci.

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“…However, there is ongoing controversy regarding the effectiveness of these combinations [13,14,17,[42][43][44]. Some clinical trials [45] support the use of everolimus as a standard immunosuppressive drug leading to reduced exposure to CNI; however, this is not universal. A recent systematic review [45] which compared mTOR with other immunosuppressants found that everolimus or sirolimus combined with a CNI prevented kidney transplant failure and rejection as effectively as other immunosuppressants combined with a CNI in short follow-up periods.…”

Section: Discussionmentioning

confidence: 99%

“…Some clinical trials [45] support the use of everolimus as a standard immunosuppressive drug leading to reduced exposure to CNI; however, this is not universal. A recent systematic review [45] which compared mTOR with other immunosuppressants found that everolimus or sirolimus combined with a CNI prevented kidney transplant failure and rejection as effectively as other immunosuppressants combined with a CNI in short follow-up periods. However, the risk of viral infections (cytomegalovirus and BK) was significantly less with mTOR combined with everolimus.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Maintenance Immunosuppression Therapies in a Matched-Pair Analysis Cohort of 16 Years of Renal Transplant in the Brazilian National Health System

Gomes

Barbosa

Godman

et al. 2020

IJERPH

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The maintenance of patients with renal transplant typically involves two or more drugs to prevent rejection and prolong graft survival. The calcineurin inhibitors (CNI) are the most commonly recommended medicines in combinations with others. While immunosuppressive treatment regimens are well established, there is insufficient long-term effectiveness data to help guide future management decisions. The study analyzes the effectiveness of treatment regimens containing CNI after renal transplantation during 16 years of follow-up with real-world data from the Brazilian National Health System (SUS). This was a retrospective study of 2318 SUS patients after renal transplantion. Patients were propensity score-matched (1:1) by sex, age, type and year of transplantation. Kaplan–Meier analysis was used to estimate the cumulative probabilities of survival. A Cox proportional hazard model was used to evaluate factors associated with progression to graft loss. Multivariable analysis, adjusted for diabetes mellitus and race/color, showed a greater risk of graft loss for patients using tacrolimus plus mycophenolate compared to patients treated with cyclosporine plus azathioprine. In conclusion, this Brazilian real-world study, with a long follow-up period using matched analysis for relevant clinical features and the representativeness of the sample, demonstrated improved long-term effectiveness for therapeutic regimens containing cyclosporine plus azathioprine. Consequently, we recommend that protocols and clinical guidelines for renal transplantation should consider the cyclosporine plus azathioprine regimen as a potential first line option, along with others.

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“…A recently published Cochrane review of 70 studies in adult KTRs found mTORi/antiproliferative regimens compared with CNI/antiproliferative regimens had little or no difference in death or malignancies, but mTORi based regimens were associated with lower rates of CMV infection and increased incidence of graft loss and AR. When CNI/mTORi regimens were compared with CNI/antiproliferative regimens, little or no difference was found in death (RR = 1.06, 95% CI = 0.84–1.33; 31 studies), graft loss (RR = 1.09, 95% CI = 0.82–1.45; 26 studies), AR (RR = 0.95, 95% CI = 0.81–1.12; 24 studies), or malignancies (RR = 0.83, 95% CI = 0.64–1.07; 17 studies), and again reduction in CMV (RR = 0.44, 95% CI = 0.34–0.58; 25 studies) was found 96 . Such robust pooled data are not available for pediatric KTRs.…”

Section: Maintenance Immunosuppression In Pediatric Kidney Transplantmentioning

confidence: 95%

Considerations and controversies of pharmacologic management of the pediatric kidney transplant recipient

2021

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Pediatric kidney transplantation has experienced considerable growth and improvement in patient and allograft outcomes over the past 20 years, in part due to advancements in immunosuppressive regimens and management. Despite this progress, care for this unique population can be challenging due to limited pediatric transplant data and trials, intricacies related to differences in children and adolescents compared with their adult counterparts, and limitations to long‐term survival facing all solid organ transplant populations. Immunosuppression and infection prevention practices vary from one pediatric transplant center to another and clinical controversies exist surrounding treatment and dosing. This review aims to summarize key aspects of pharmacologic management in this population and present pertinent data that describe the influence of practice to serve as a resource for practitioners caring for this unique specialty patient population. Additionally, this review highlights select controversies that exist within pediatric kidney transplantation.

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Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients

Abstract: Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients (Review)

Cited by 31 publications

References 257 publications

Timing of mTORI usage and outcomes in kidney transplant recipients

Timing of mTORI usage and outcomes in kidney transplant recipients

Effectiveness of Maintenance Immunosuppression Therapies in a Matched-Pair Analysis Cohort of 16 Years of Renal Transplant in the Brazilian National Health System

Considerations and controversies of pharmacologic management of the pediatric kidney transplant recipient

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