Maximizing the clinical outcome with mTOR inhibitors in the renal transplant recipient: Defining the role of calcineurin inhibitors

Transplant International

Volumn 17, Issue 6, 2004, Pages 279-285

  Nashan, Björn ^a  

^a DALHOUSIE UNIVERSITY   (Canada)

Author keywords

Calcineurin inhibitor; Cyclosporin A; Everolimus; mTOR inhibitor; Rejection; Sirolimus

Indexed keywords

AZATHIOPRINE; BASILIXIMAB; CALCINEURIN INHIBITOR; CYCLOSPORIN A; EVEROLIMUS; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 2 RECEPTOR ANTIBODY; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; RAPAMYCIN; STEROID; TARGET OF RAPAMYCIN KINASE; UNCLASSIFIED DRUG;

CLINICAL TRIAL; DOSE RESPONSE; DRUG POTENTIATION; DRUG WITHDRAWAL; DYSPNEA; EDEMA; GRAFT REJECTION; HUMAN; HYPERLIPIDEMIA; HYPERTENSION; HYPERURICEMIA; HYPOKALEMIA; HYPOMAGNESEMIA; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY FUNCTION; KIDNEY GRAFT; LEUKOPENIA; LIVER TOXICITY; NEPHROTOXICITY; PNEUMONIA; PRIORITY JOURNAL; REVIEW; THROMBOCYTOPENIA;

CALCINEURIN; DRUG THERAPY, COMBINATION; ENZYME INHIBITORS; GRAFT REJECTION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; PROTEIN KINASES;

EID: 3943062287     PISSN: 09340874     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1432-2277.2004.tb00444.x     Document Type: Review

References (42)

1. Vincenti F, Ramos E, Brattstrom C. Multicenter trial exploring calcineurin inhibitors avoidance in renal transplantation. Transplantation 2001; 71:1282.
2. Abramowicz D, Manas D, Lao M, et al. Cyclosporine withdrawal from a mycophenolate mofetil-containing immunosuppressive regimen in stable kidney transplant recipients: a randomized, controlled study. Transplantation 2002; 74:1725.
3. Leggat JE, Ojo AO, Leichtman AB, et al. Long-term renal allograft survival: prognostic implication of the timing of acute rejection episodes. Transplantation 1997; 63:1268.
4. Ducloux D, Motte G, Billerey C, et al. Cyclosporin withdrawal with concomitant conversion from azathioprine to mycophenolate mofetil in renal transplant recipients with chronic allograft nephropathy: a 2-year follow-up. Transplant Int 2002; 15:387.
5. Pascual M, Curtis J, Delmonico FL, et al. A prospective, randomized clinical trial of cyclosporine reduction in stable patients greater than 12 months after renal transplantation. Transplantation 2003; 75:1501.
6. Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem 1998; 31:335.
7. Sehgal SN. Rapamune (sirolimus, rapamycin): an overview and mechanism of action. Ther Drug Monitor 1995; 17:660.
8. Schuler W, Sedrani R, Cottens S, et al. SDZ RAD, a new rapamycin derivative: pharmacokinetic properties in vitro and in vivo. Transplantation 1997; 64:36.
9. Bohler T, Waiser J, Budde K, et al. The in vivo effect of rapamycin derivative SDZ RAD on lymphocyte proliferation. Transplant Proc 1998; 30:2195.
10. Ikonen TS, Gummet JF, Hayase M, et al. Sirolimus (rapamycin) halts and reverses progression of allograft vascular disease in non-human primates. Transplantation 2000; 70:969.
11. Schuurman H-J, Cottens S, Fuchs S, et al. SDZ RAD, a new rapamycin derivative: synergism with cyclosporine. Transplantation 1997; 64:32.
12. Schuurman J-J, Ringers J, Schuler W, et al. Oral efficacy of the macrolide immunosuppressant SDZ RAD and of cyclosporine microemulsion in cynomolgus monkey kidney allotransplantation. Transplantation 2000; 69:737.
13. Hausen B, Boeke K, Berry GJ, et al. Suppression of acute rejection in allogeneic rat lung transplantation: a study for the efficacy and pharmacokinetics of rapamycin derivative (SDZ RAD) used alone and in combination with a microemulsion formulation of cyclosporine. J Heart Lung Transplant 1999; 18:150.
14. Groth CG, Backman L, Morales JM. Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Transplant Study Group. Transplantation 1999; 67:1036.
15. Kreis H, Cisterne JM, Land W, et al. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation 2000; 69:1252.
16. Rapamune Prescribing Information, Wyeth Pharmaceuticals www.emc.medicines.org.uk Accessed: 7 August 2003.
17. Rapamune Prescribing Information, Wyeth www.Wyeth.com Accessed: 7 August 2003.
18. MacDonald AS for the Rapamune Global Study Group. A worldwide, phase III, randomized, controlled safety and efficacy study of a sirolimus/cyclosporine regimen for prevention of acute rejection in recipients of primary mismatched renal allografts. Transplantation 2001; 71:271.
19. Kahan BD for The Rapamune US Study Group. Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: A randomized multicentre study. Lancet 2000; 356:194.
20. Vitko S, Margreiter R, Weimar W, et al. and the RAD 201 Study Group. International, double-blind, parallel-group study of the safety and efficacy of Certican (RAD) versus mycophenolate mofetil (MMF) in combination with Neoral and steroids. Am J Transplant 2001; (Suppl 1): 474.
21. Kaplan B, Tedesco-Silva H, Mendez R, et al., and the RAD 251 Study Group. North/South American, double-blind, parallel group study of the safety and efficacy of Certican (RAD) versus mycophenolate mofetil (MMF) in combination with Neoral and corticosteroids. Am J Transplant 2001; (Suppl 1): 475.
22. Kahan BD. Two-year results of multicenter phase III trials on the effect of the addition of sirolimus to cyclosporine-based immunosuppressive regimens in renal transplantation. Transplant Proc 2003; 35 (Suppl): S37.
23. Oppenheimer F, Oyen O, Viljoen, et al. 36-month results of an international study with everolimus for the prevention of allograft rejection in de novo kidney transplant recipients. Am J Transplant 2003; 3 (Suppl 5). Abstract 1201
24. Gonwa TA, Hricik DE, Brinker K, et al. Improved renal function in sirolimus-treated renal transplant patients after early cyclosporine elimination. Transplantation 2002; 74:1560.
25. Johnson RWG, Kreis H, Oberbauer R, et al. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 2001; 72:777.
26. Oberbauer R, Kreis H, Johnson RWG, et al. Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients: 2-year results of the rapamune maintenance regimen study. Transplantation 2003; 76:364.
27. Paczek L, Dedochova J, Matl I, Pohanka E. An open non-comparative pilot study of renal function after conversion from cyclosporine (CsA) to sirolimus (SRL) in stable renal allograft recipients with mild to moderate renal insufficiency. Am J Transplant 2003; 3 (Suppl 5). Abstract 258.
28. Nashan B, Curtis J, Ponticelli C, et al. Everolimus and reduced exposure cyclosporine in de novo renal transplant recipients: a 7-3 year phase II, randomized, multicenter, open-label study. Transplantation 2004 (in press)
29. Mahalati K, Belitsky P, West K, et al. Approaching the therapeutic window for cyclosporine in kidney transplantation: a prospective study. J Am Soc Nephrol 2001; 12:823.
30. International Neoral Renal Transplantation Study Group. Cyclosporine microemulsion (Neoral) absorption profiling and sparse-sample predictors during the first 3 months after renal transplantation. Am J Transplant 2002; 2:148.
31. 2 monitoring of cyclosporine microemulsion (Neoral). Transplantation 2003; 76:903.
32. Vitko S, Tedesco H, Eris J, et al. Everolimus With Optimized Cyclosporine Dosing in Renal Transplant Recipients: 6-Month Safety and Efficacy Results of Two Randomized Studies. Am J Transplant 2004; 4:626.
33. Baloobal K. A Phase III prospective, randomized study to evaluate concentration-controlled sirolimus (Rapamune) with cyclosporine dose minimization or elimination at six months in 87 de novo renal allograft recipients. Transplantation 2003; 75:1404.
34. Jardine AG. 12 month results of a phase III prospective, randomised study to evaluate concentration controlled rapamune with cyclosporin dose minimization or elimination in de novo renal allograft recipients. Am J Transplant 2003; 3 (Suppl 5). Abstract 1206.
35. Halloran PF, Helms LMH, Kung L, Noujaim J. The temporal profile of calcineurin inhibition by cyclosporine in vivo. Transplantation 1999; 68:1356.
36. Sindhi R, LaVia MF, Paulling E, et al. Stimulated response of peripheral lymphocytes may distinguish cyclosporine effect in renal transplant recipients receiving a cyclosporine + rapamycin regimen. Transplantation 2000; 69:432.
37. Baan CC, Boelaars-van Haperen MJAM, van Riemskijk IC, van der Plas AJ, Weimer W. IL-7 and IL-15 bypass the immunosuppressive action of anti-CD25 monoclonal antibodies. Transplant Proc 2001; 33:2244.
38. Nashan B. Early clinical experience with a novel rapamycin derivative. Ther Drug Monitor 2002; 24:53.
39. Whelchel JD. Therapeutic drug monitoring (TDM) for everolimus: modeling of efficacy based on two kidney transplantation trials with implemented TDM. Am J Transplant 2003; 3 (Suppl 5). Abstract 1163.
40. Weir MR, Ward MT, Blahut SA, et al. Long-term impact of discontinued or reduced calcineurin inhibitor in patients with chronic allograft nephropathy. Kidney Int 2001; 59:1567.
41. Diekmann F, Budde K, Torregrosa JV, et al. Improvement of renal transplant function in patients with chronic calcineurin-inhibitor (CNI) nephrotoxicity and low proteinuria one year after conversion to sirolimus (SRL). Am J Transplant 2003; 3 (Suppl 5): Abstract 181.
42. 2 monitoring in the long-term management of renal transplant recipients. Transplantation 2003; 75:1089.