The role of tacrolimus in renal transplantation

Tacrolimus gained FDA approval for use in liver transplantation in 1994 and, approximately 3 years later, was approved for the prevention of acute rejection in kidney transplantation. Over the last decade tacrolimus has become the calcineurin inhibitor of choice for the prevention of rejection in renal transplantation. The objective of this study was to provide a review and update of the literature on the use of tacrolimus in renal transplantation. Numerous clinical trials have shown tacrolimus to be superior to cyclosporine in the prevention of acute rejection and recent trials have demonstrated superiority of tacrolimus over cyclosporine in terms of allograft survival. Post-transplant diabetes remains more common with tacrolimus than cyclosporine, despite lower doses of both tacrolimus and corticosteroids. A novel once-daily dosage form of tacrolimus has recently been developed and is approved for use in Europe. Tacrolimus remains an important immunosuppressant for the prevention of acute rejection. The prolonged-release formulation may improve compliance and possibly long-term outcomes.

[1]  Daniel C. Brennan,et al.  A Randomized, Prospective, Pharmacoeconomic Trial of Tacrolimus versus Cyclosporine in Combination with Thymoglobulin in Renal Transplant Recipients , 2005, Transplantation.

[2]  Eld,et al.  COMPARISON OF MORTALITY IN ALL PATIENTS ON DIALYSIS , PATIENTS ON DIALYSIS AWAITING TRANSPLANTATION , AND RECIPIENTS OF A FIRST CADAVERIC TRANSPLANT , 2000 .

[3]  P. Halloran,et al.  Reduced exposure to calcineurin inhibitors in renal transplantation. , 2007, The New England journal of medicine.

[4]  P. Kuo,et al.  One‐Year Results with Extended‐Release Tacrolimus/MMF, Tacrolimus/MMF and Cyclosporine/MMF in De Novo Kidney Transplant Recipients , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[5]  J. H. Harrison,et al.  Successful homotransplantation of the human kidney between identical twins. , 1956, Journal of the American Medical Association.

[6]  R. Wolfe,et al.  Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. , 1999, The New England journal of medicine.

[7]  J. Schold,et al.  Lack of Improvement in Renal Allograft Survival Despite a Marked Decrease in Acute Rejection Rates Over the Most Recent Era , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[8]  L. Makowka,et al.  A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression in liver transplantation: The U.S. Multicenter FK506 Liver Study Group. N Engl J Med 1994;331:1110–1115 , 1995 .

[9]  J. Squifflet,et al.  The Effects of FK778 in Combination With Tacrolimus and Steroids: A Phase II Multicenter Study in Renal Transplant Patients , 2004, Transplantation.

[10]  T. Theruvath,et al.  Strategies to improve long-term outcomes after renal transplantation. , 2002, The New England journal of medicine.

[11]  M. Okuhara,et al.  FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. , 1987, The Journal of antibiotics.

[12]  CONVERSION OF STABLE KIDNEY TRANSPLANT RECIPIENTS FROM A TWICE DAILY PROGRAF BASED REGIMEN TO A ONCE DAILY MODIFIED RELEASE TACROLIMUS BASED REGIMEN , 2004, Transplantation proceedings.

[13]  J. Pirsch,et al.  A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group. , 1997, Transplantation.

[14]  V. Dharnidharka.  Costimulation blockade with belatacept in renal transplantation. , 2005, The New England journal of medicine.

[15]  H. Sollinger.  Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group. , 1995, Transplantation.

[16]  A. Matas,et al.  Two years postconversion from a prograf-based regimen to a once-daily tacrolimus extended-release formulation in stable kidney transplant recipients. , 2007, Transplantation.

[17]  R. Balshaw,et al.  New Onset Diabetes Mellitus in Patients Receiving Calcineurin Inhibitors: A Systematic Review and Meta‐Analysis , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[18]  M. Stegall,et al.  Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation. , 2000, Transplantation.

[19]  H. Jeon,et al.  Financial Analysis of Potential Donor Management at a Medicare‐Approved Transplant Hospital , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[20]  C. Rosso Felipe,et al.  Immunotherapy for De Novo renal transplantation: what's in the pipeline? , 2006, Drugs.

[21]  D. Hricik,et al.  Improved Renal Function after Conversion from Tacrolimus/Sirolimus to Tacrolimus/Mycophenolate Mofetil in Kidney Transplant Recipients , 2006, Transplantation.

[22]  M. Pescovitz,et al.  A Phase I/II Randomized Open‐Label Multicenter Trial of Efalizumab, a Humanized Anti‐CD11a, Anti‐LFA‐1 in Renal Transplantation , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[23]  M. Stegall,et al.  RANDOMIZED TRIAL OF TACROLIMUS PLUS MYCOPHENOLATE MOFETIL OR AZATHIOPRINE VERSUS CYCLOSPORINE ORAL SOLUTION (MODIFIED) PLUS MYCOPHENOLATE MOFETIL AFTER CADAVERIC KIDNEY TRANSPLANTATION: RESULTS AT 2 YEARS1 , 2001, Transplantation.

[24]  R. Rapp.  Pharmacokinetics and Pharmacodynamics of Intravenous and Oral Azithromycin: Enhanced Tissue Activity and Minimal Drug Interactions , 1998, The Annals of pharmacotherapy.

[25]  I. Bekersky,et al.  Effect of Time of Meal Consumption on Bioavailability of a Single Oral 5 mg Tacrolimus Dose , 2001, Journal of clinical pharmacology.

[26]  N. Undre,et al.  Pharmacokinetics of tacrolimus: clinically relevant aspects. , 1999, Transplantation proceedings.

[27]  R. Margreiter.  Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study , 2002, The Lancet.

[28]  T. Mathew.  A blinded, long-term, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation: results at three years. Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. , 1998, Transplantation.

[29]  F. Vincenti,et al.  Tacrolimus (FK 506) in kidney transplantation: five-year survival results of the U.S. multicenter, randomized, comparative trial. , 2001, Transplantation proceedings.

[30]  K. Budde,et al.  Corticosteroid-Free Immunosuppression with Tacrolimus, Mycophenolate Mofetil, and Daclizumab Induction in Renal Transplantation , 2005, Transplantation.

[31]  C. Hengstenberg,et al.  Cardiovascular Risk Factors and Estimated Risk for CAD in a Randomized Trial Comparing Calcineurin Inhibitors in Renal Transplantation , 2003, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[32]  J. Barry,et al.  The effect of conversion from cyclosporine to tacrolimus on gingival hyperplasia, hirsutism and cholesterol. , 2000, Transplantation.

[33]  S. Hariharan,et al.  Improved graft survival after renal transplantation in the United States, 1988 to 1996. , 2000, The New England journal of medicine.

[34]  W. Weimar,et al.  Mycophenolic acid plasma concentrations in kidney allograft recipients with or without cyclosporin: a cross-sectional study. , 1999, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[35]  D Talbot,et al.  Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. , 1997, Transplantation.

[36]  N. Undre.  Pharmacokinetics of tacrolimus-based combination therapies. , 2003, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[37]  H. Meier‐Kriesche,et al.  Renal transplantation: a half century of success and the long road ahead. , 2004, Journal of the American Society of Nephrology : JASN.

[38]  M. Salvadori,et al.  Randomized Controlled Trial of FTY720 Versus MMF in De Novo Renal Transplantation , 2006, Transplantation.

[39]  W. Weimar,et al.  Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients. , 1999, Transplantation.

[40]  J. Alexander,et al.  Reduced inter- and intrasubject variability in cyclosporine pharmacokinetics in renal transplant recipients treated with a microemulsion formulation in conjunction with fasting, low-fat meals, or high-fat meals. , 1995, Transplantation.

[41]  L. Furian,et al.  Co-administration of sirolimus alters tacrolimus pharmacokinetics in a dose-dependent manner in adult renal transplant recipients. , 2006, Pharmacological research.

[42]  S. Läer,et al.  [Drug interactions of tacrolimus]. , 2006, Medizinische Monatsschrift fur Pharmazeuten.

[43]  R. Wiesner,et al.  A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. A report of the Tacrolimus Kidney Transplantation Rescue Study Group. , 1996, Transplantation.

[44]  M. Salvadori,et al.  FTY720 versus MMF with Cyclosporine in de novo Renal Transplantation: A 1‐Year, Randomized Controlled Trial in Europe and Australasia , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[45]  M. Okuhara,et al.  Physicochemical properties of FK-506, a novel immunosuppressant isolated from Streptomyces tsukubaensis. , 1987, Transplantation proceedings.

[46]  A. Demetris,et al.  Outcome of tacrolimus conversion therapy for renal allograft rejection: 5-year follow-up. , 1999, Transplantation proceedings.

[47]  J. Chapman,et al.  Calcineurin Inhibitor Nephrotoxicity: Longitudinal Assessment by Protocol Histology , 2004, Transplantation.

[48]  L Timmermann,et al.  The mechanism of action of cyclosporin A and FK506. , 1996, Clinical immunology and immunopathology.

[49]  G. Klintmalm,et al.  Use of Prograf (FK 506) as rescue therapy for refractory rejection after liver transplantation. US Multicenter FK 506 Liver Study Group. , 1993, Transplantation proceedings.

[50]  M. Sayegh,et al.  Transplantation 50 years later--progress, challenges, and promises. , 2004, The New England journal of medicine.

[51]  M. Kemper,et al.  Neuropsychologic side‐effects of tacrolimus in pediatric renal transplantation , 2003, Clinical transplantation.

[52]  F. Cosio,et al.  Growing Pains from The Islet Cell Transplant World , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[53]  G. Tufveson,et al.  Mycophenolate mofetil in renal transplantation: 3-year results from the placebo-controlled trial. European Mycophenolate Mofetil Cooperative Study Group. , 1999, Transplantation.

[54]  A. Mayer,et al.  Chronic rejection and graft half-life: five-year follow-up of the European Tacrolimus Multicenter Renal Study. , 2002, Transplantation proceedings.

[55]  Joshua Miller,et al.  A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years. , 2002, Transplantation.

[56]  M. Sayegh,et al.  Immunosuppressive strategies in transplantation , 1999, The Lancet.

[57]  S. Jensik.  Tacrolimus (FK 506) in kidney transplantation: three-year survival results of the US multicenter, randomized, comparative trial. FK 506 Kidney Transplant Study Group. , 1998, Transplantation proceedings.

[58]  A. Demetris,et al.  Clinical features of acute reversible tacrolimus (FK 506) nephrotoxicity in kidney transplant recipients. , 1997, Clinical transplantation.

[59]  Joshua Miller,et al.  A Comparison Of Tacrolimus (fk506) And Cyclosporine For Immunosuppression After Cadaveric Renal Transplantation1 , 1997 .

[60]  P. Rutgeerts,et al.  Cytochrome P450 3A4 and P‐glycoprotein Activity and Assimilation of Tacrolimus in Transplant Patients with Persistent Diarrhea , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[61]  T. Mathew.  A Blinded, Long-term, Randomized Multicenter Study Of Mycophenolate Mofetil In Cadaveric Renal Transplantation: Results at Three Years1,2 , 1998 .

[62]  H. Tedesco-Silva,et al.  Long-term kidney transplant outcomes in patients receiving oil-based or microemulsion formulations of cyclosporine. , 2004, Transplantation Proceedings.

[63]  U. Christians,et al.  The pharmacokinetics and metabolic disposition of tacrolimus: A comparison across ethnic groups , 2001, Clinical pharmacology and therapeutics.

[64]  L. Hilbrands,et al.  Reduced exposure to calcineurin inhibitors in renal transplantation. , 2008, The New England journal of medicine.