Everolimus with low‐dose tacrolimus in simultaneous pancreas and kidney transplantation

Abstract

The efficacy and safety of everolimus (EVR) in simultaneous pancreas and kidney transplantation (SPKT) is unclear. We retrospectively evaluated 25 consecutive SPKT recipients at our center from November 2011 to March 2013. All patients received dual induction (Thymoglobulin/basiliximab) and low-dose tacrolimus plus corticosteroids. Nine patients who received EVR were compared with 14 patients who received enteric-coated mycophenolate sodium (EC-MPS); two patients who received sirolimus were excluded from the analysis. With a median follow-up of 14 months, the pancreas graft survival rate was 100% in both groups, and the kidney graft survival rate was 100% and 93% in EVR and EC-MPS patients, respectively. One EC-MPS patient lost her kidney graft from proteinuric kidney disease. Another EC-MPS patient received treatment for clinically diagnosed pancreas and kidney graft rejection. No rejection was observed in EVR patients. Serum creatinine and HbA1c levels were similar between the groups. There was no significant difference of surgical or medical complications. In conclusion, EVR seems to provide comparable short-term outcome to EC-MPS when combined with low-dose tacrolimus/steroids and dual induction therapy. A larger study with a longer follow-up is required to further assess this combination.

Conversion from tacrolimus‐mycophenolate mofetil to tacrolimus‐mTOR immunosuppression after kidney‐pancreas transplantation reduces the incidence of both BK and CMV viremia

“…The mechanism of the antiviral effect of the TAC/mTOR immunosuppression regimen is likely twofold: via a reduction in the dose of tacrolimus and possibly through a direct action on viral replication by mTOR inhibition. In both this report and the renal/pancreas transplant studies previously discussed, the tacrolimus dose was reduced when used in combination with a mTOR inhibitor . It has been previously shown that tacrolimus‐based immunosuppression is an important factor in the emergence of BK viremia after renal transplantation .…”

“…A long‐term study from the University of Miami randomized KP recipients at the time of transplantation between TAC‐sirolimus and TAC‐MMF and demonstrated equivalent patient and graft survivals at 10 years post‐transplantation. Another report from that institution similarly showed no difference in outcomes at 1 year between TAC‐everolimus and TAC‐MMF cohorts . Other reports have noted comparable surgical complication rates to tacrolimus‐based immunosuppression and excellent graft survivals .…”

“…13 Another report from that institution similarly showed no difference in outcomes at 1 year between TACeverolimus and TAC-MMF cohorts. 14,15 Other reports have noted comparable surgical complication rates to tacrolimus-based immunosuppression and excellent graft survivals. 16,17 Additionally, we have previously reported on the use of mTOR-based immunosuppression in KP transplantation, demonstrating excellent outcomes, but did not study the incidence of viral infections.…”

“…In both this report and the renal/ pancreas transplant studies previously discussed, the tacrolimus dose was reduced when used in combination with a mTOR inhibitor. 5,7,15 It has been previously shown that tacrolimus-based immunosuppression is an important factor in the emergence of BK viremia after renal transplantation. 23 Moreover, the principle mechanism for treatment of BK infection is via reduction in the dose of tacrolimus.…”

Everolimus Improves Microcirculatory Derangements in Experimental Postischemic Pancreatitis Modulating the Expression of Vascular Endothelial Growth Factor, Interleukin 6, and Toll-Like Receptor 4

“…There are limited reports on its use in clinical pancreas transplantation. 21,22 The influence of mTOR inhibition on IRI is contradictory. Mammalian target of rapamycin inhibition has been protective in IRI of the heart.…”