Early withdrawal of calcineurin inhibitors and everolimus monotherapy in de novo liver transplant recipients preserves renal function

Am J Transplant. 2010 Oct;10(10):2252-62. doi: 10.1111/j.1600-6143.2010.03128.x. Epub 2010 Sep 3.

Abstract

We designed a randomized trial to assess whether the early withdrawal of cyclosporine (CsA) followed by the initiation of everolimus (Evr) monotherapy in de novo liver transplantation (LT) patients would result in superior renal function compared to a CsA-based immunosuppression protocol. All patients were treated with CsA for the first 10 days and then randomized to receive Evr in combination with CsA up to day 30, then either continued on Evr monotherapy (Evr group) or maintained on CsA with/without mycophenolate mofetil (CsA group) in case of chronic kidney disease (CKD). Seventy-eight patients were randomized (Evr n = 52; CsA n = 26). The 1-year freedom from efficacy failure in Evr group was 75% versus 69.2% in CsA group, p = 0.36. There was no statistically significant difference in patient survival between the two groups. Mean modification of diet in renal disease (MDRD) was significantly better in the Evr group at 12 months (87.7 ± 26.1 vs. 59.9 ± 12.6 mL/min; p < 0.001). The incidence of CKD stage ≥ 3 (estimated glomerular filtration rate < 60 mL/min) was higher in the CsA group at 1 year (52.2% vs. 15.4%, p = 0.005). The results indicate that early withdrawal of CsA followed by Evr monotherapy in de novo LT patients is associated with an improvement in renal function, with a similar incidence of rejection and major complications.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Calcineurin Inhibitors*
  • Cyclosporine / administration & dosage
  • Cyclosporine / adverse effects*
  • Dyslipidemias / drug therapy
  • Dyslipidemias / etiology
  • Everolimus
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Kidney Function Tests
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Renal Insufficiency / prevention & control*
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • Sirolimus