Tailoring tacrolimus therapy in kidney transplantation

Expert Rev Clin Pharmacol. 2018 Jun;11(6):581-588. doi: 10.1080/17512433.2018.1479638. Epub 2018 May 25.

Abstract

The prevalence of end-stage renal disease is increasing worldwide. The best treatment is kidney transplantation, although life-long immunosuppressive therapy is then mandatory. Currently, the cornerstone immunosuppressive therapy relies on tacrolimus (Tac), a calcineurin inhibitor that is nephrotoxic but whose exposition can be minimized in a delicate balance. Area covered: We addressed whether, in the setting of kidney transplantation, Tac-based therapy can be tailored to medical needs: to achieve this, we searched for suitable articles in PubMed. Expert commentary: Too over-minimization of Tac, when associated with mycophenolic acid (MPA), may cause the development of de novo donor-specific alloantibodies (DSA). However, Tac minimization, in the context of everolimus-associated therapy instead of MPA, does not increase DSA formation as demonstrated in the TRANSFORM study and, in addition, can prevent cytomegalovirus (CMV) infection/reactivation. Nonetheless, Tac therapy, regardless of its formulation (immediate or extended release) compared to cyclosporine A, increases the risk of posttransplant diabetes mellitus; this increase is not affected by steroid therapy. Tac-based immunosuppression remains the best immunosuppressive therapy in kidney-transplant recipients and can be tailored according to patients' need.

Keywords: Kidney transplantation; everolimus; minimization; posttransplant diabetes; tacrolimus.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Calcineurin Inhibitors / administration & dosage
  • Calcineurin Inhibitors / adverse effects
  • Cyclosporine / administration & dosage
  • Everolimus / administration & dosage
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Kidney Failure, Chronic / surgery
  • Kidney Transplantation / methods*
  • Mycophenolic Acid / administration & dosage
  • Tacrolimus / administration & dosage*
  • Tacrolimus / adverse effects

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • Mycophenolic Acid
  • Tacrolimus