An update on chemical pharmacotherapy options for the prevention of kidney transplant rejection with a focus on costimulation blockade

Expert Opin Pharmacother. 2017 Jun;18(8):799-807. doi: 10.1080/14656566.2017.1323876. Epub 2017 May 9.

Abstract

The introduction of calcineurin inhibitors (CNI) has greatly improved graft survival in the past three decades. However, long-term graft survival is still limited due to chronic allograft injury and side-effects of immunosuppressive medication. Areas covered: The present overview gives an update on pharmacotherapeutic strategies after kidney transplantation. The main focus is on CNI-sparing regimens using co-stimulatory blockade and on new substances on the horizone. Expert opinion: CNI sparing regimens are well-established. Complete CNI avoidance after kidney transplantation was often associated with impaired graft survival until the approval of the co-stimulation blocker belatacept for de novo immunosuppression after kidney transplantation. Concerns still exist with respect to severe T-cell-mediated rejection episodes in the early phase after transplantation. Thus, a triple drug regimen with CNI, mycophenolic acid and steroids still represents the gold-standard of immunosuppressive therapy. Alternative substances expand the possibilities of tailoring individual immunosuppression for different indications such as biopsy-proven CNI toxicity, polyoma virus BK nephropathy or CNI-triggered thrombotic microangiopathy. However, a change of the immunosuppressive therapy must always be balanced against each patient´s individual immunological risk in order to address the importance of chronic antibody-mediated rejection driven by donor specific antibodies (DSA).

Keywords: Kidney transplantation; belatacept; calcineurin inhibitors; chronic antibody-mediated rejection; immunosuppressive regimens; mammalian target of rapamycin inhibitors.

Publication types

  • Review

MeSH terms

  • Abatacept / administration & dosage
  • Abatacept / adverse effects
  • Abatacept / therapeutic use
  • Calcineurin Inhibitors / administration & dosage
  • Calcineurin Inhibitors / adverse effects
  • Calcineurin Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Humans
  • Immunosuppression Therapy / methods*
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Interleukin-2 / pharmacology
  • Kidney Diseases / drug therapy
  • Kidney Diseases / surgery
  • Kidney Transplantation / methods*
  • Mycophenolic Acid / therapeutic use
  • Steroids / therapeutic use
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Interleukin-2
  • Steroids
  • Abatacept
  • Mycophenolic Acid