Dataset Information

Mammalian Target of Rapamycin Inhibitors and Kidney Function After Thoracic Transplantation: A Systematic Review and Recommendations for Management of Lung Transplant Recipients.

ABSTRACT:

Background

Chronic kidney disease (CKD) after lung transplantation is common and limits the survival of transplant recipients. The calcineurin inhibitors (CNI), cyclosporine A, and tacrolimus being the cornerstone of immunosuppression are key mediators of nephrotoxicity. The mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, are increasingly used in combination with reduced CNI dosage after lung transplantation.

Methods

This systematic review examined the efficacy and safety of mTOR inhibitors after lung transplantation and explored their effect on kidney function.

Results

mTOR inhibitors are often introduced to preserve kidney function. Several clinical trials have demonstrated improved kidney function and efficacy of mTOR inhibitors. The potential for kidney function improvement and preservation increases with early initiation of mTOR inhibitors and low target levels for both mTOR inhibitors and CNI. No defined stage of CKD for mTOR inhibitor initiation exists, nor does severe CKD preclude the improvement of kidney function under mTOR inhibitors. Baseline proteinuria may negatively predict the preservation and improvement of kidney function. Discontinuation rates of mTOR inhibitors due to adverse effects increase with higher target levels.

Conclusions

More evidence is needed to define the optimal immunosuppressive regimen incorporating mTOR inhibitors after lung transplantation. Not only the indication criteria for the introduction of mTOR inhibitors are needed, but also the best timing, target levels, and possibly discontinuation criteria must be defined more clearly. Current evidence supports the notion of nephroprotective potential under certain conditions.

SUBMITTER: Schmucki K

PROVIDER: S-EPMC9746343 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Mammalian Target of Rapamycin Inhibitors and Kidney Function After Thoracic Transplantation: A Systematic Review and Recommendations for Management of Lung Transplant Recipients.

Schmucki Katja K Hofmann Patrick P Fehr Thomas T Inci Ilhan I Kohler Malcolm M Schuurmans Macé M MM

Transplantation 20221208 1

<h4>Background</h4>Chronic kidney disease (CKD) after lung transplantation is common and limits the survival of transplant recipients. The calcineurin inhibitors (CNI), cyclosporine A, and tacrolimus being the cornerstone of immunosuppression are key mediators of nephrotoxicity. The mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, are increasingly used in combination with reduced CNI dosage after lung transplantation.<h4>Methods</h4>This systematic review examined the e ...[more]

PMID: 36508646

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Project description:Background and objectivesEmerging evidence from recently published observational studies and an individual patient data meta-analysis shows that mammalian target of rapamycin inhibitor use in kidney transplantation is associated with increased mortality. Therefore, all-cause mortality and allograft loss were compared between use and nonuse of mammalian target of rapamycin inhibitors in patients from Australia and New Zealand, where mammalian target of rapamycin inhibitor use has been greater because of heightened skin cancer risk.Design, setting, participants, & measurementsOur longitudinal cohort study included 9353 adult patients who underwent 9558 kidney transplants between January 1, 1996 and December 31, 2012 and had allograft survival ≥1 year. Risk factors for all-cause death and all-cause and death-censored allograft loss were analyzed by multivariable Cox regression using mammalian target of rapamycin inhibitor as a time-varying covariate. Additional analyses evaluated mammalian target of rapamycin inhibitor use at fixed time points of baseline and 1 year.ResultsPatients using mammalian target of rapamycin inhibitors were more likely to be white and have a history of pretransplant cancer. Over a median follow-up of 7 years, 1416 (15%) patients died, and 2268 (24%) allografts were lost. There was a higher risk of all-cause mortality with time-varying mammalian target of rapamycin inhibitor use (hazard ratio, 1.47; 95% confidence interval, 1.23 to 1.76) as well as in the fixed time model analyses comparing mammalian target of rapamycin inhibitor use at baseline (hazard ratio, 1.54; 95% confidence interval, 1.22 to 1.93) and 1 year (hazard ratio, 1.63; 95% confidence interval, 1.32 to 2.01). Time-varying mammalian target of rapamycin inhibitor use was associated with higher risk of death because of malignancy (hazard ratio, 1.37; 95% confidence interval, 1.09 to 1.71). There were no statistically significant differences in the risk of all-cause (hazard ratio, 0.98; 95% confidence interval, 0.85 to 1.12) and death-censored (hazard ratio, 0.85; 95% confidence interval, 0.69 to 1.03) allograft loss between the mammalian target of rapamycin inhibitor use and nonuse groups in the time-varying model as well as the fixed time models.ConclusionsMammalian target of rapamycin inhibitor use was associated with a higher risk of all-cause mortality but not allograft loss.

Project description:Background and objectivesOlder kidney transplant recipients are susceptible to cognitive impairment, frailty, comorbidities, immunosuppression-related complications, and chronic graft failure, however, there has been limited focus on their concerns and expectations related to transplantation. This study aims to describe the perspectives of older kidney transplant recipients about their experience of kidney transplantation, self-management, and treatment goals to inform strategies and interventions that address their specific needs.Design, setting, participants, & measurementsFace-to-face semistructured interviews were conducted with 30 kidney transplant recipients aged 65-80 years from five renal units in Australia. Transcripts were analyzed thematically.ResultsSix themes were identified: restoring vitality of youth (with subthemes of revived mindset for resilience, embracing enjoyment in life, drive for self-actualization); persisting through prolonged recovery (yielding to aging, accepting functional limitations, pushing the limit, enduring treatment responsibilities); imposing sicknesses (combatting devastating comorbidities, painful restrictions, emerging disillusionment, anxieties about accumulating side effects, consuming treatment burden); prioritizing graft survival (privileged with a miracle, negotiating risks for longevity, enacting a moral duty, preserving the last opportunity); confronting health deterioration (vulnerability and helplessness, narrowing focus to immediate concerns, uncertainty of survival); and value of existence (purpose through autonomy, refusing the burden of futile treatment, staying alive by all means).ConclusionsOlder kidney transplant recipients felt able to enjoy life and strived to live at their newly re-established potential and capability, which motivated them to protect their graft. However, some felt constrained by slow recuperation and overwhelmed by unexpected comorbidities, medication-related side effects, and health decline. Our findings suggest the need to prepare and support older recipients for self-management responsibilities, clarify their expectations of post-transplant risks and outcomes, and provide assistance through prolonged recovery after kidney transplantation.

Dataset Information

Mammalian Target of Rapamycin Inhibitors and Kidney Function After Thoracic Transplantation: A Systematic Review and Recommendations for Management of Lung Transplant Recipients.

Background

Methods

Results

Conclusions

Publications

Mammalian Target of Rapamycin Inhibitors and Kidney Function After Thoracic Transplantation: A Systematic Review and Recommendations for Management of Lung Transplant Recipients.

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