title: Tofacitinib in kidney transplantation.
abstract: BACKGROUND
  This review will discuss the mechanism of action and important kidney transplant clinical trial data for the small molecule Janus kinase (JAK) 3 inhibitor tofacitinib , formerly known as CP-690,550 and tasocitinib.
  
  
  METHODS
  Successful kidney transplantation requires adequate immunosuppression. Current maintenance immunosuppressive protocols which rely on calcineurin inhibitors have long-term nephrotoxicity and negative impact on cardiometabolic risk factors. JAKs are cytoplasmic tyrosine kinases that participate in the signaling of a broad range of cell surface receptors, particularly members of the cytokine receptor common gamma (cγ) chain family. JAK3 inhibition has immunosuppressive effects and treatment with tofacitinib in clinical trials has demonstrated efficacy in autoimmune disorders such as psoriasis and rheumatoid arthritis. Nonhuman primate models of renal transplantation demonstrated prolonged graft survival with tofacitinib compared to control. Renal transplant clinical trials in humans have demonstrated tofacitinib to be noninferior to cyclosporine in terms of rejection rates and graft survival. There was also a lower rate of new onset diabetes after transplant. However, there was a trend toward more infections, including cytomegalovirus and BK virus nephritis.
  
  
  CONCLUSIONS
  Tofacitinib may be a promising alternative to calcineurin inhibitors. The optimal therapeutic window is still being determined.
authors.affiliation: University of California, Kidney Transplant Service, San Francisco, CA 94143-0780, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wojciechowski
authors.forename: Flavio
authors.initials: F
authors.lastname: Vincenti
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors; D016030:Kidney Transplantation / Q000379:methods*; D058990:Molecular Targeted Therapy; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053616:Janus Kinase 3