Conversion to Everolimus in Liver Transplant Patients With Renal Dysfunction

Pérez, Tomás; Segovia, Roberto; Castro, Lorena; Roblero, Juan Pablo; Estela, Ricardo

doi:10.1016/j.transproceed.2011.06.009

Cited by 8 publications

(6 citation statements)

References 16 publications

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“…The combination of EVR with low‐dose TAC initiated within 4 weeks after LT has been shown to preserve kidney function in many observational studies . Recently, this observation has been strengthened by the publication of a few well‐designed RCTs examining early initiation of EVR with subsequent CNI minimization or discontinuation …”

Section: Discussionmentioning

confidence: 99%

Everolimus with early withdrawal or reduced‐dose calcineurin inhibitors improves renal function in liver transplant recipients: A systematic review and meta‐analysis

Lin

Mittal

Sahebjam

et al. 2017

Clinical Transplantation

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Calcineurin inhibitors (CNI) are the mainstay of immunosuppression after liver transplantation (LT), but CNIs are associated with significant nephrotoxicity. Recently, mTOR inhibitors such as sirolimus and everolimus (EVR) have been used with or without CNIs in LT recipients for their renal-sparing effect. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) that examined the effect of EVR with CNI minimization or withdrawal on renal function in LT recipients. RCT of primary adult LT recipients with baseline GFR >30 mL/min who received EVR with CNI minimization or withdrawal were included. Four RCTs (EVR n=465, control n=428) were included. In three RCTs, EVR was initiated 4 weeks following LT; these studies were used to assess the primary outcome. All four studies were used to assess the secondary outcomes. Based on this study, EVR use with CNI minimization in LT recipients is associated with improved renal function at 12 months by GFR of 10.2 mL/min (95% CI: 2.75-17.8). EVR use was not associated with an increased risk of biopsy-proven acute rejection (RR 0.68, 95% CI: 0.31-1.46), graft loss (RR 1.60, 95% CI: 0.51-5.00), or mortality (RR 1.34, 95% CI 0.62-2.90). However, it was associated with an increased risk of overall infections (RR 1.45, 95% CI: 1.10-1.91).

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Section: Discussionmentioning

confidence: 99%

Everolimus with early withdrawal or reduced‐dose calcineurin inhibitors improves renal function in liver transplant recipients: A systematic review and meta‐analysis

Lin

Mittal

Sahebjam

et al. 2017

Clinical Transplantation

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“…Many observational studies reported that combining everolimus (EVR) with a low dose of tacrolimus (TAC) within 4 weeks after LT contributed to preserving kidney function. (11)(12)(13) This observation was strengthened by the results of a few well-designed, randomized, controlled trials on early EVR initiation (1 month after transplant) with subsequent CNI minimization or discontinuation. (5,8,14,15) However, very early (between 1 week and 1 month) EVR-facilitated CNI reduction or discontinuation has not been deeply investigated because of concerns of increased rejection rate (16) and evidence of an increased risk of hepatic artery thrombosis (sirolimus).…”

Section: Original Article | 243mentioning

confidence: 98%

“…Recent evidence indicates that the combination of CNIs with mammalian target of rapamycin (mTOR) inhibitors guarantees a proper immunosuppression and offers the opportunity to minimize CNI exposure, thus providing a rational basis to reduce or discontinue CNI exposure before an irreversible renal deterioration occurs. Many observational studies reported that combining everolimus (EVR) with a low dose of tacrolimus (TAC) within 4 weeks after LT contributed to preserving kidney function . This observation was strengthened by the results of a few well‐designed, randomized, controlled trials on early EVR initiation (1 month after transplant) with subsequent CNI minimization or discontinuation …”

mentioning

confidence: 99%

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial

et al. 2019

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Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open‐label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6‐12 ng/mL. The primary endpoint was the proportion of treated biopsy‐proven acute rejection (tBPAR)–free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR‐free (P = 0.09); composite endpoint‐free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial.

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“…Some of these protocols include switching from CNI-based immunosuppression to immunosuppressive regimens based on inhibitors of mechanistic target of rapamycin (mTOR) or combinations of mTOR inhibitors with reduced doses of CNIs. Although these strategies can lead to reduced nephrotoxicity and improved renal function [9,10], CNI-free immunosuppressive regimens have been associated with a higher risk for acute graft rejection [11,12]. This study was designed to evaluate the course of renal function during the first 24 months after conversion from a CNI (tacrolimus or cyclosporine) to an mTOR inhibitor (sirolimus or everolimus).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors

et al. 2015

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Background:Renal dysfunction often occurs in liver transplant (LT) recipients receiving calcineurin inhibitor (CNI)-based immunosuppressive regimens, increasing morbidity and mortality rates. Replacement of CNIs by mTOR inhibitorbased immunosuppressive protocols may prevent renal impairment in LT recipients. Material/Methods:Outcomes in patients who underwent LT between 1996 and 2010 at our center and who were switched from CNI-based to mTOR inhibitor-based immunosuppression were retrospectively analyzed. Renal course, hyperlipidemia, and graft rejection were assessed in patients maintained on this CNI-free regimen for at least 24 months. Results:Of the 85 patients switched from CNI-based to mTOR inhibitor-based, CNI-free immunosuppression, 78 met the inclusion criteria. Within the first 6 weeks after switching, the covariable adjusted estimated glomerular filtration rate (eGFR) increased 5.6 mL/min [95% confidence interval 2.6-8.7 mL/min, p<0.001], but there were no further statistically noticeable changes in eGFR. Concentrations of cholesterol and triglycerides increased statistically, noticeable within the first 12 months after drug conversion. Histologically proven graft rejection was observed in 4 patients (5.1%) after conversion. Conclusions:Conversion from CNI-based to CNI-free, mTOR inhibitor-based immunosuppression after LT is safe and can result in significant renal recovery. CNI-free, mTOR inhibitor-based immunosuppression is a potential option for patients with contraindications for CNIs and for LT recipients with rapid reduction in kidney function due to CNIs.

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Conversion to Everolimus in Liver Transplant Patients With Renal Dysfunction

Cited by 8 publications

References 16 publications

Everolimus with early withdrawal or reduced‐dose calcineurin inhibitors improves renal function in liver transplant recipients: A systematic review and meta‐analysis

Everolimus with early withdrawal or reduced‐dose calcineurin inhibitors improves renal function in liver transplant recipients: A systematic review and meta‐analysis

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial

Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors

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