Immunosuppressive therapy after kidney transplantation: Current and new strategies

Minerva Urologica e Nefrologica

Volumn 63, Issue 1, 2011, Pages 1-19

  Metalidis, C ^a   Kuypers, D R ^a  

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

Author keywords

Immunosuppression; Kidney failure, chronic; Kidney transplantation

Indexed keywords

3' AZIDO 2',3' DIDEOXY 5 METHYLCYTIDINE; ALEFACEPT; AZATHIOPRINE; BASILIXIMAB; BELATACEPT; CALCINEURIN INHIBITOR; CORTICOSTEROID; CYCLOSPORIN; CYCLOSPORIN A; DACLIZUMAB; EFALIZUMAB; EVEROLIMUS; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; RAPAMYCIN; SOTRASTAURIN; TACROLIMUS; TASOCITINIB; VOCLOSPORIN;

ACUTE GRAFT REJECTION; CARDIOVASCULAR RISK; CYTOMEGALOVIRUS INFECTION; DIABETES MELLITUS; DRUG DOSE ESCALATION; DRUG RESPONSE; DRUG WITHDRAWAL; DYSLIPIDEMIA; GLUCOSE BLOOD LEVEL; GRAFT SURVIVAL; HODGKIN DISEASE; HUMAN; HYPERTENSION; IMMUNOSUPPRESSIVE TREATMENT; INCIDENCE; INFECTION; KAPOSI SARCOMA; KIDNEY CARCINOMA; KIDNEY DYSFUNCTION; KIDNEY TRANSPLANTATION; LEUKEMIA; LOW DRUG DOSE; NEPHROTOXICITY; NONHUMAN; PATHOPHYSIOLOGY; PHARMACOGENETICS; POLYOMAVIRUS INFECTION; REVIEW; RISK FACTOR; SIDE EFFECT; SURVIVAL RATE; TREATMENT OUTCOME;

CALCINEURIN; FORECASTING; HUMANS; IMMUNOSUPPRESSION; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; MYCOPHENOLIC ACID; PHARMACOGENETICS; POSTOPERATIVE CARE;

EID: 79956303263     PISSN: 03932249     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (106)

1. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999;341:1725-30.
2. SRTR. Scientific Registry of Transplant Recipients [Internet]. Available from www.ustransplant.org [cited 2010, Feb 21.
3. Howard RJ, Patton PR, Reed AI, Hemming AW, Van der Werf WJ, Pfaff WW et al. The changing causes of graft loss and death after kidney transplantation. Transplantation 2002;73:1923-8. (Pubitemid 34701001)
4. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 2003;3:178-85. (Pubitemid 36323115)
5. Kasiske B, Cosio FG, Beto J, Bolton K, Chavers BM, Grimm R Jr et al. Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Am J Transplant 2004;4 Suppl 7:13-53. (Pubitemid 38436863)
6. Heit JJ, Apelqvist AA, Gu X, Winslow MM, Neilson JR, Crabtree GR et al. Calcineurin/NFAT signalling regulates pancreatic beta-cell growth and function. Nature 2006;443:345-9. (Pubitemid 44435154)
7. de Groen PC. Cyclosporine, low density lipoprotein, and cholesterol. Mayo Clinic Proceedings 1988;1012.
8. Vincenti F, Friman S, Scheuermann E, Rostaing L, Jenssen T, Campistol JM et al. Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus. Am J Transplant 2007;7:1506-14. (Pubitemid 46776239)
9. Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet 2004;43:623-53. (Pubitemid 38981845)
10. Lowance D, Neumayer HH, Legendre CM, Squifflet JP, Kovarik J, Brennan PJ et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N Engl J Med 1999;340:1462-70.
11. Wiseman AC. Polyomavirus nephropathy: a current perspective and clinical considerations. Am J Kidney Dis 2009;54:131-42.
12. Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007;357:2601-14. (Pubitemid 350294226)
13. Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant 2004;4:905-13. (Pubitemid 38745589)
14. Buell JF, Gross TG, Woodle ES. Malignancy after transplantation. Transplantation 2005;80(2 Suppl):S254-S264.
15. Hojo M, Morimoto T, Maluccio M, Asano T, Morimoto K, Lagman M et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 1999;397:530-4.
16. Guba M, Graeb C, Jauch KW, Geissler EK. Pro- and anticancer effects of immunosuppressive agents used in organ transplantation. Transplantation 2004;77:1777-82. (Pubitemid 38822196)
17. Kurtz A, Della BR, Kuhn K. Cyclosporine A enhances renin secretion and production in isolated juxtaglomerular cells. Kidney Int 1988;33:947-53.
18. Textor SC, Burnett JC, Jr., Romero JC, Canzanello VJ, Taler SJ, Wiesner R et al. Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation. Kidney Int 1995;47:1426-33.
19. Hocherl K, Kees F, Kramer BK, Kurtz A. Cyclosporine A attenuates the natriuretic action of loop diuretics by inhibition of renal COX-2 expression. Kidney Int 2004;65:2071-80. (Pubitemid 38669993)
20. Hortelano S, Castilla M, Torres AM, Tejedor A, Bosca L. Potentiation by nitric oxide of cyclosporin A and FK506-induced apoptosis in renal proximal tubule cells. J Am Soc Nephrol 2000;11:2315-23.
21. Djamali A. Oxidative stress as a common pathway to chronic tubulointerstitial injury in kidney allografts. Am J Physiol Renal Physiol 2007;293:F445-F455. (Pubitemid 47358116)
22. Longoni B, Boschi E, Demontis GC, Ratto GM, Mosca F. Apoptosis and adaptive responses to oxidative stress in human endothelial cells exposed to cyclosporin A correlate with BCL-2 expression levels. FASEB J 2001;15:731-40. (Pubitemid 32245991)
23. Khanna A, Plummer M, Bromberek C, Bresnahan B, Hariharan S. Expression of TGF-beta and fibrogenic genes in transplant recipients with tacrolimus and cyclosporine nephrotoxicity. Kidney Int 2002;62: 2257-63. (Pubitemid 35366184)
24. Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;349:931-40. (Pubitemid 37064766)
25. Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med 2003;349: 2326-33. (Pubitemid 37509740)
26. Vincenti F, Ramos E, Brattstrom C, Cho S, Ekberg H, Grinyo J et al. Multicenter trial exploring calcineurin inhibitors avoidance in renal transplantation. Transplantation 2001;71:1282-7. (Pubitemid 32507148)
27. Asberg A, Midtvedt K, Line PD, Narverud J, Holdaas H, Jenssen T et al. Calcineurin inhibitor avoidance with daclizumab, mycophenolate mofetil, and prednisolone in DR-matched de novo kidney transplant recipients. Transplantation 2006;82:62-8. (Pubitemid 44296979)
28. Kreis H, Cisterne JM, Land W, Wramner L, Squifflet JP, Abramowicz D et al. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation 2000;69:1252-60. (Pubitemid 30238708)
29. Groth CG, Bäckman L, Morales JM, Calne R, Kreis H, Lang P et al. Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group. Transplantation 1999;67:1036-42.
30. Flechner SM, Kobashigawa J, Klintmalm G. Calcineurin inhibitor-sparing regimens in solid organ transplantation: focus on improving renal function and nephrotoxicity. Clin Transplant 2008;22:1-15. (Pubitemid 351149996)
31. Larson TS, Dean PG, Stegall MD, Griffin MD, Textor SC, Schwab TR et al. Complete avoidance of calcineurin inhibitors in renal transplantation: a randomized trial comparing sirolimus and tacrolimus. Am J Transplant 2006;6:514-22. (Pubitemid 43382137)
32. Ekberg H, Tedesco-Silva H, Demirbas A, Vitko S, Nashan B, Gürkan A et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007;357:2562-75. (Pubitemid 350294223)
33. Kaplan B, Schold JD, Meier-Kriesche HU. Long-term graft survival with neoral and tacrolimus: a paired kidney analysis. J Am Soc Nephrol 2003;14:2980-4. (Pubitemid 37305662)
34. Solez K, Vincenti F, Filo RS. Histopathologic findings from 2-year protocol biopsies from a U.S. multicenter kidney transplant trial comparing tarolimus versus cyclosporine: a report of the FK506 Kidney Transplant Study Group. Transplantation 1998;66:1736-40. (Pubitemid 29035001)
35. Srinivas TR, Schold JD, Guerra G, Eagan A, Bucci CM, Meier-Kriesche HU. Mycophenolate mofetil/sirolimus compared to other common immunosuppressive regimens in kidney transplantation. Am J Transplant 2007;7:586-94. (Pubitemid 46376441)
36. Flechner S., Glyda M., Steinberg S. A randomized, open-label study to compare the safety and efficacy of two different sirolimus regimens with a tacrolimus and mycophenolate mofetil regimen in de novo renal allograft recipients: acute rejection and graft survival results from the ORION study. Am J Transplant 2007;7(suppl 2):160.
37. Rush D, Nickerson P, Gough J, McKenna R, Grimm P, Cheang M et al. Beneficial effects of treatment of early subclinical rejection: a randomized study. J Am Soc Nephrol 1998;9:2129-34. (Pubitemid 28482163)
38. Oberbauer R, Segoloni G, Campistol JM, Kreis H, Mota A, Lawen J et al. Early cyclosporine withdrawal from a sirolimus-based regimen results in better renal allograft survival and renal function at 48 months after transplantation. Transpl Int 2005;18:22-8. (Pubitemid 41742941)
39. Mota A, Arias M, Taskinen EI, Paavonen T, Brault Y, Legendre C et al. Sirolimus-based therapy following early cyclosporine withdrawal provides significantly improved renal histology and function at 3 years. Am J Transplant 2004;4:953-61. (Pubitemid 38745595)
40. Stallone G, Di Paolo S, Schena A, Infante B, Grandaliano G, Battaglia M et al. Early withdrawal of cyclosporine A improves 1-year kidney graft structure and function in sirolimus-treated patients. Transplantation 2003;75:998-1003. (Pubitemid 36438529)
41. Ciancio G, Burke GW, Gaynor JJ, Ruiz P, Roth D, Kupin W et al. A randomized long-term trial of tacrolimus/sirolimus versus tacrolimums/ mycophenolate versus cyclosporine/sirolimus in renal transplantation: three-year analysis. Transplantation 2006;81:845-52.
42. Meier-Kriesche HU, Schold JD, Srinivas TR, Howard RJ, Fujita S, Kaplan B. Sirolimus in combination with tacrolimus is associated with worse renal allograft survival compared to mycophenolate mofetil combined with tacrolimus. Am J Transplant 2005;5:2273-80. (Pubitemid 41648476)
43. Anglicheau D, Pallet N, Rabant M, Marquet P, Cassinat B, Méria P et al. Role of P-glycoprotein in cyclosporine cytotoxicity in the cyclosporine-sirolimus interaction. Kidney Int 2006;70:1019-25. (Pubitemid 44344071)
44. Ekberg H, Grinyó J, Nashan B, Vanrenterghem Y, Vincenti F, Voulgari A et al. Cyclosporine sparing with mycophenolate mofetil, daclizumab and corticosteroids in renal allograft recipients: the CAESAR Study. Am J Transplant 2007;7:560-70. (Pubitemid 46376436)
45. Weir MR, Mulgaonkar S, Pearson T. Mycophenolate mofetil/sirolimus maintenance therapy after calcineurin inhibitor withdrawal in renal transplant recipients: two-year outcomes of the Spare the Nephron (STN) trial (Abstract 33). Paper presented at: American Transplant Congress;May 30-June 3, 2009;Boston, MA. 2009.
46. Servais A, Meas-Yedid V, Toupance O, Lebranchu Y, Thierry A, Moulin B et al. Interstitial fibrosis quantification in renal transplant recipients randomized to continue cyclosporine or convert to sirolimus. Am J Transplant 2009;9:2552-60.
47. McAlister VC, Gao Z, Peltekian K, Domingues J, Mahalati K, MacDonald AS. Sirolimus-tacrolimus combination immunosuppression. Lancet 2000;355: 376-7.
48. Grinyo JM, Campistol JM, Paul J, Paul J, García- Martínez J, Morales JM et al. Pilot randomized study of early tacrolimus withdrawal from a regimen with sirolimus plus tacrolimus in kidney transplantation. Am J Transplant 2004;4:1308-14. (Pubitemid 39013578)
49. Morales JM, Grinyó JM, Campistol JM, García-Martínez J, Arias M, Paul J et al. Improved renal function, with similar proteinuria, after two years of early tacrolimus withdrawal from a regimen of sirolimus plus tacrolimus. Transplantation 2008;86:620-2.
50. Abramowicz D, del Carmen RM, Vitko S, del Castillo D, Manas D, Lao M et al. Cyclosporine withdrawal from a mycophenolate mofetil-containing immunosuppressive regimen: results of a five-year, prospective, randomized study. J Am Soc Nephrol 2005;16: 2234-40. (Pubitemid 41716457)
51. Dudley C, Pohanka E, Riad H, Dedochova J, Wijngaard P, Sutter C et al. Mycophenolate mofetil substitution for cyclosporine a in renal transplant recipients with chronic progressive allograft dysfunction: the "creeping creatinine" study. Transplantation 2005;79:466-75.
52. Schena FP, Pascoe MD, Alberu J, del Carmen Rial M, Oberbauer R, Brennan DC et al. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation 2009;87:233-42.
53. Guba M, von BP, Steinbauer M, Koehl G, Flegel S, Hornung M et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 2002;8:128-35. (Pubitemid 34155123)
54. Weir MR, Blahut S, Drachenburg C, Young C, Papademitriou J, Klassen DK et al. Late calcineurin inhibitor withdrawal as a strategy to prevent graft loss in patients with suboptimal kidney transplant function. Am J Nephrol 2004;24:379-86. (Pubitemid 39279378)
55. Ekberg H, Bernasconi C, Tedesco-Silva H, Vítko S, Hugo C, Demirbas A et al. Calcineurin inhibitor minimization in the Symphony study: observational results 3 years after transplantation. Am J Transplant 2009;9: 1876-85.
56. Myers BD, Newton L, Boshkos C, Macoviak JA, Frist WH, Derby GC et al. Chronic injury of human renal microvessels with low-dose cyclosporine therapy. Transplantation 1988;46:694-703. (Pubitemid 19017044)
57. Mycophenolate mofetil in renal transplantation: 3- year results from the placebo-controlled trial. European Mycophenolate Mofetil Cooperative Study Group. Transplantation 1999;68:391-6.
58. Knight SR, Russell NK, Barcena L, Morris PJ. Mycophenolate mofetil decreases acute rejection and may improve graft survival in renal transplant recipients when compared with azathioprine: a systematic review. Transplantation 2009;87:785-94.
59. Kuypers DR, Le Meur Y, Cantarovich M, Tredger MJ, Tett SE, Cattaneo D et al. Consensus Report on Therapeutic Drug Monitoring of Mycophenolic Acid in Solid Organ Transplantation. Clin J Am Soc Nephrol 2010;5:341-58.
60. Kiberd BA, Lawen J, Fraser AD, Keough-Ryan T, Belitsky P. Early adequate mycophenolic acid exposure is associated with less rejection in kidney transplantation. Am J Transplant 2004;4:1079-83. (Pubitemid 38868597)
61. van Gelder T, Le Meur Y, Shaw LM, Oellerich M, DeNofrio D, Holt C et al. Therapeutic drug monitoring of mycophenolate mofetil in transplantation. Ther Drug Monit 2006;28:145-54. (Pubitemid 44314941)
62. Gaston RS, Kaplan B, Shah T, Cibrik D, Shaw LM, Angelis M et al. Fixed- or controlled-dose mycophenolate mofetil with standard- or reduced-dose calcineurin inhibitors: the Opticept trial. Am J Transplant 2009;9:1607-19.
63. van Gelder T., Hilbrands LB, Vanrenterghem Y, Weimar W, de Fijter JW, Squifflet J et al. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation. Transplantation 1999;68:261-6. (Pubitemid 29360288)
64. Le Meur Y., Buchler M, Thierry A, Gaillard S, Villemain F, Lavaud S et al. Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patient outcomes after renal transplantation. Am J Transplant 2007;7:2496-503. (Pubitemid 47566324)
65. van Gelder T, Silva HT, de Fijter JW, Budde K, Kuypers D, Tyden G et al. Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration-controlled trial. Transplantation 2008;86:1043-51.
66. van Gelder T, Silva HT, de Fijter JW, Budde K, Kuypers D, Tyden G et al. Renal transplant patients at high risk of acute rejection benefit from adequate exposure to mycophenolic acid. Transplantation 2008;86: 1043-51.
67. Pascual J, Quereda C, Zamora J, Hernandez D. Steroid withdrawal in renal transplant patients on triple therapy with a calcineurin inhibitor and mycophenolate mofetil: a meta-analysis of randomized, controlled trials. Transplantation 2004;78:1548-56. (Pubitemid 39552943)
68. Rostaing L, Cantarovich D, Mourad G, Budde K, Rigotti P, Mariat C et al. Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation. Transplantation 2005;79:807-14. (Pubitemid 40546200)
69. Woodle ES, First MR, Pirsch J, Shihab F, Gaber AO, Van VP. A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Ann Surg 2008;248:564-77.
70. Kumar MS, Heifets M, Moritz MJ, Saeed MI, Khan SM, Fyfe B et al. Safety and efficacy of steroid withdrawal two days after kidney transplantation: analysis of results at three years. Transplantation 2006;81:832-39.
71. Halloran PF, Helms LM, Rung L, Noujaim J. The temporal profile of calcineurin inhibition by cyclosporine in vivo. Transplantation 1999;68:1356-61.
72. Boleslawski E, Conti F, Sanquer S, Podevin P, Chouzenoux S, Batteux F et al. Defective inhibition of peripheral CD8+ T cell IL-2 production by anti-calcineurin drugs during acute liver allograft rejection. Transplantation 2004;77:1815-20. (Pubitemid 38822202)
73. Glander P, Hambach P, Braun KP, Fritsche L, Waiser J, Mai I et al. Effect of mycophenolate mofetil on IMP dehydrogenase after the first dose and after long-term treatment in renal transplant recipients. Int J Clin Pharmacol Ther 2003;41:470-6. (Pubitemid 37258865)
74. Glander P, Hambach P, Braun KP, Fritsche L, Giessing M, Mai I et al. Pre-transplant inosine monophosphate dehydrogenase activity is associated with clinical outcome after renal transplantation. Am J Transplant 2004;4:2045-51. (Pubitemid 39611633)
75. Stein CM, Murray JJ, Wood AJ. Inhibition of stimulated interleukin-2 production in whole blood: a practical measure of cyclosporine effect. Clin Chem 1999;45:1477-84. (Pubitemid 29419000)
76. Hodge G, Hodge S, Reynolds P, Holmes M. Intracellular cytokines in blood T cells in lung transplant patients - a more relevant indicator of immunosuppression than drug levels. Clin Exp Immunol 2005;139: 159-64. (Pubitemid 40066142)
77. Hartel C, Schumacher N, Fricke L, Ebel B, Kirchner H, Muller-Steinhardt M. Sensitivity of whole-blood T lymphocytes in individual patients to tacrolimus (FK 506): impact of interleukin-2 mRNA expression as surrogate measure of immunosuppressive effect. Clin Chem 2004;50:141-51. (Pubitemid 38125711)
78. Stalder M, Birsan T, Holm B, Haririfar M, Scandling J, Morris RE. Quantification of immunosuppression by flow cytometry in stable renal transplant recipients. Ther Drug Monit 2003;25:22-7. (Pubitemid 36139821)
79. Kowalski R, Post D, Schneider MC, Britz J, Thomas J, Deierhoi M et al. Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management. Clin Transplant 2003;17:77-88. (Pubitemid 36833776)
80. Kowalski RJ, Post DR, Mannon RB, Sebastian A, Wright HI, Sigle G et al. Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay. Transplantation 2006;82:663-8. (Pubitemid 44395237)
81. Cadillo-Chavez R, de ES, Santiago-Delpin EA, Rodríguez-Trinidad AT, Camacho-Carrazo B, Alfaro T et al. Assessing the risk of infection and rejection in Hispanic renal transplant recipients by means of an adenosine triphosphate release assay. Transplant Proc 2006;38: 918-20.
82. Zeevi A, Britz JA, Bentlejewski CA, Guaspari D, Tong W, Bond G et al. Monitoring immune function during tacrolimus tapering in small bowel transplant recipients. Transpl Immunol 2005;15:17-24. (Pubitemid 41435099)
83. Hesselink DA, van Schaik RH, van der Heiden IP, van der Werf M, Gregoor PJ, Lindemans J et al. Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther 2003;74:245-54.
84. Haufroid V, Mourad M, Van Kerckhove V, Wawrzyniak J, De Meyer M, Eddour DC et al. The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenetics 2004;14:147-54. (Pubitemid 38373108)
85. Kuypers DR, de JH, Naesens M, Lerut E, Verbeke K, Vanrenterghem Y. CYP3A5 and CYP3A4 but not MDR1 single-nucleotide polymorphisms determine long-term tacrolimus disposition and drug-related nephrotoxicity in renal recipients. Clin Pharmacol Ther 2007;82:711-25. (Pubitemid 350114816)
86. Hesselink DA, van Schaik RH, van AM, van Agteren M, de Fijter JW, Hartmann A, Zeier M et al. CYP3A5 genotype is not associated with a higher risk of acute rejection in tacrolimus-treated renal transplant recipients. Pharmacogenet Genomics 2008;18:339-48. (Pubitemid 351367527)
87. van Schaik RH, van Agteren M, de Fijter JW, Hartmann A, Schmidt J, Budde K et al. UGT1A9 -275T>A/- 2152C>T polymorphisms correlate with low MPA exposure and acute rejection in MMF/tacrolimus-treated kidney transplant patients. Clin Pharmacol Ther 2009;86:319-27.
88. Vincenti F, Klintmalm G, Halloran PF. Open letter to the FDA: new drug trials must be relevant. Am J Transplant 2008;8:733-4. (Pubitemid 351347744)
89. Pondrom S. Location, Location, Location. Am J Transplant 2009;9:2207-8.
90. Ghoreschi K, Laurence A, O'Shea JJ. Janus kinases in immune cell signaling. Immunol Rev 2009;228: 273-87.
91. Changelian PS, Flanagan ME, Ball DJ et al. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 2003;302:875-8. (Pubitemid 37339629)
92. van Gurp E., Weimar W, Gaston R, Brennan D, Mendez R, Pirsch J et al. Phase 1 dose-escalation study of CP-690 550 in stable renal allograft recipients: preliminary findings of safety, tolerability, effects on lymphocyte subsets and pharmacokinetics. Am J Transplant 2008;8:1711-8.
93. Busque S, Leventhal J, Brennan DC, Steinberg S, Klintmalm G, Shah T et al. Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP- 690,550: a pilot study in de novo kidney allograft recipients. Am J Transplant 2009;9:1936-45.
94. Aspeslet L, Freitag D, Trepanier D, Abel M, Naicker S, Kneteman N et al. ISA(TX)247: a novel calcineurin inhibitor. Transplant Proc 2001;33:1048-51.
95. Gaber AO, Busque S, Mulgaonkar S. ISA247: A phase HB multicenter, open label, concentration-controlled trial in de nove renal transplantation (abstract LB06). Am J Transplant 2008;8(suppl2):336.
96. Papp K, Bissonnette R, Rosoph L, Wasel N, Lynde CW, Searles G et al. Efficacy of ISA247 in plaque psoriasis: a randomised, multicentre, double-blind, placebo-controlled phase III study. Lancet 2008;371: 1337-42. (Pubitemid 351522314)
97. Bigaud M, Wieczorek G, Riesen S. NVP-AEB071 (AEB), a novel inhibitor of early T-cell activation, prolongs the survival of non-human primate kidney allografts when used as monotherapy or at non-effective doses combined with a non-effective dose of cyclosporine (abstract). Am J Transplant 2006;6(Suppl 2):250.
98. Vincenti F. Costimulation blockade in autoimmunity and transplantation. J Allergy Clin Immunol 2008;121: 299-306.
99. Vincenti F, Larsen C, Durrbach A, Wekerle T, Nashan B, Blancho G et al. Costimulation blockade with belatacept in renal transplantation. N Engl J Med 2005;353: 770-81. (Pubitemid 41215486)
100. Pondrom S. The AJT report: News and issues that affect organ and tissue transplantation. Belatacept results promising...with some caveats. Am J Transplant 2009;9:2445-6.
101. Nicolls MR, Gill RG. LFA-1 (CD11a) as a therapeutic target. Am J Transplant 2006;6:27-36. (Pubitemid 43382197)
102. Vincenti F, Mendez R, Pescovitz M, Rajagopalan PR, Wilkinson AH, Butt K et al. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Am J Transplant 2007;7:1770-7. (Pubitemid 46905435)
103. Posselt A, Szot G, Frassetto L. Islet allograft survival in type 1 diabetics using a calcineurin-free protocol based on efalizumab and sirolimus (abstract #216). Am J Transplant 2008;8(Suppl 2):235.
104. da Silva AJ, Brickelmaier M, Majeau GR, Li Z, Su L, Hsu YM et al. Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J Immunol 2002;168:4462-71. (Pubitemid 34441348)
105. Krueger GG. Clinical response to alefacept: results of a phase 3 study of intravenous administration of alefacept in patients with chronic plaque psoriasis. J Eur Acad Dermatol Venereol 2003;17 Suppl 2: 17-24. (Pubitemid 36869296)
106. Weaver TA, Charafeddine AH, Agarwal A, Turner AP, Russell M, Leopardi FV et al. Alefacept promotes costimulation blockade based allograft survival in non- human primates. Nat Med 2009;15:746-9.