Comparison of Cyclosporine and Sirolimus Effects on Serum Creatinine Level Over Five Years After Kidney Transplantation

Soleimani, Alireza; Kamkar, I.; Nikoueinejad, Hassan; Moraweji, A.R.

doi:10.1016/j.transproceed.2013.01.060

Cited by 5 publications

(2 citation statements)

References 31 publications

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“…In summary, the SMART, CONCEPT, STN, and CONVERT trials demonstrated similar patient and graft survival in patients who converted to sirolimus. However, these and other related studies have not demonstrated a consistent long‐term renal function benefit of converting to sirolimus . Patients converting to sirolimus tended to be at higher risk of discontinuation and adverse events, such as edema, hyperlipidemia, and NODAT, although the risk of malignancy was notably lower compared with patients continuing CNI therapy.…”

Section: Converting To Mtor Inhibitors: Studies and Remaining Questionsmentioning

confidence: 76%

Conversion from calcineurin inhibitor–based immunosuppression to mammalian target of rapamycin inhibitors or belatacept in renal transplant recipients

Mulgaonkar

Kaufman

2014

Clinical Transplantation

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The calcineurin inhibitors (CNIs) remain the standard of care for maintenance immunosuppression following renal transplantation. CNIs have demonstrated their effectiveness in reducing acute cellular rejection; however, some evidence suggests that these compounds negatively affect native renal function and are associated with allograft injury in renal transplant recipients. CNIs have also been linked with hypertension, new-onset diabetes after transplantation, tremor, and thrombotic microangiopathy, which have significant consequences for long-term allograft function and patient health overall. Thus, converting patients to a non-CNI-based regimen may improve renal function and also provide extrarenal benefits. A number of studies have been conducted that explore CNI conversion strategies in renal transplant recipients in an effort to improve long-term allograft function and survival. These include converting to alternative, non-nephrotoxic, maintenance immunosuppressants, such as the mammalian target of rapamycin inhibitors (sirolimus and everolimus) and the costimulation blocker belatacept. In this review of literature, evidence for the potential renal and extrarenal benefits of conversion to these non-CNI-based regimens is evaluated. Clinical challenges, including the adverse event profiles of non-CNI-based regimens and the selection of candidates for conversion, are also examined.

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Section: Converting To Mtor Inhibitors: Studies and Remaining Questionsmentioning

confidence: 76%

Conversion from calcineurin inhibitor–based immunosuppression to mammalian target of rapamycin inhibitors or belatacept in renal transplant recipients

Mulgaonkar

Kaufman

2014

Clinical Transplantation

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“…All these findings suggest that SRL may be beneficial for long-term CNI-exposed KT patients. However, most studies on CNI-to-SRL conversion have investigated the early post-transplant period [ 8 - 11 ], and there is little information on SRL conversion in patients with long follow-up periods. Therefore, we evaluated the safety and immunologic advantages of SRL conversion in long-term CNI-exposed KT recipients with stable graft function.…”

Section: Introductionmentioning

confidence: 99%

Safety and immunologic benefits of conversion to sirolimus in kidney transplant recipients with long-term exposure to calcineurin inhibitors

Kim

et al. 2016

Korean J Intern Med

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Background/Aims:Sirolimus (SRL) is a promising immunosuppressant replacingcalcineurin inhibitors (CNIs). This study was performed to evaluate the safetyand immunologic benefits of conversion to SRL in stable kidney transplant (KT)recipients exposed to CNIs for long periods.Methods:Fourteen CNI-treated KT recipients with stable renal function for morethan 10 years were included. Either 2 or 3 mg per day of SRL was administeredwhile CNIs were reduced by half starting on day 1, and then stopped 2 weeks afterSRL introduction. The safety of SRL conversion was assessed considering thegraft function, acute rejection, and graft loss. Immunologic alterations were measuredvia serial changes of T cell and B cell subsets after SRL conversion. Adverseeffects of SRL conversion were also evaluated.Results:Conversion to SRL was successful in nine patients (64.2%). Conversionto SRL preserved graft function as compared to the baseline value (p = 0.115). Noacute rejection or allograft loss was observed during the follow-up period. Immunemonitoring of T and B cells revealed a regulatory T cells increase after SRL conversion (p = 0.028). Most adverse events developed within 6 weeks after SRLconversion, and oral mucositis was the main cause of SRL withdrawal.Conclusions:Conversion to SRL can be safe and has immunologic benefits in KTrecipients with long-term CNI exposure. Close monitoring of mucocutaneous adverseevents is, however, required in the early period after SRL conversion.

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Sirolimus effects on cancer incidence after kidney transplantation: a meta‐analysis

2015

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Sirolimus, an immunosuppressant option for kidney transplant recipients, may reduce cancer risk by interrupting the mammalian target of rapamycin pathway. However, studies of sirolimus and cancer incidence in kidney recipients have not been definitive, and have had limited ability to examine specific cancer types. The literature was systematically reviewed to identify randomized controlled trials (RCTs) and observational studies of kidney recipients that compared sirolimus users to sirolimus nonusers. Meta-analytic methods were used to obtain pooled estimates of the association between sirolimus use and incidence of total cancer and specific cancer types. Estimates were stratified by study type (RCT vs. observational) and use of cyclosporine (an immunosuppressant that affects DNA repair). Twenty RCTs and two observational studies were eligible for meta-analysis, including 39,039 kidney recipients overall. Sirolimus use was associated with lower overall cancer incidence (incidence rate ratio [IRR] = 0.71, 95% CI = 0.56–0.90), driven by a reduction in incidence of nonmelanoma skin cancer (NMSC, IRR = 0.49, 95% CI = 0.32–0.76). The protective effect of sirolimus on NMSC risk was most notable in studies comparing sirolimus against cyclosporine (IRR = 0.19, 95% CI = 0.04–0.84). After excluding NMSCs, there was no overall association between sirolimus and incidence of other cancers (IRR = 1.06, 95% CI = 0.69–1.63). However, sirolimus use had associations with lower kidney cancer incidence (IRR = 0.40, 95% CI = 0.20–0.81), and higher prostate cancer incidence (IRR = 1.85, 95% CI = 1.17–2.91). Among kidney recipients, sirolimus users have lower NMSC risk, which may be partly due to removal of cyclosporine. Sirolimus may also reduce kidney cancer risk but did not appear protective for other cancers, and it may actually increase prostate cancer risk.

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Comparison of Cyclosporine and Sirolimus Effects on Serum Creatinine Level Over Five Years After Kidney Transplantation

Cited by 5 publications

References 31 publications

Conversion from calcineurin inhibitor–based immunosuppression to mammalian target of rapamycin inhibitors or belatacept in renal transplant recipients

Conversion from calcineurin inhibitor–based immunosuppression to mammalian target of rapamycin inhibitors or belatacept in renal transplant recipients

Safety and immunologic benefits of conversion to sirolimus in kidney transplant recipients with long-term exposure to calcineurin inhibitors

Sirolimus effects on cancer incidence after kidney transplantation: a meta‐analysis

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