Cyclosporine: Molecular Action to Clinical Therapeutics

Immunotherapy in Transplantation: Principles and Practice

Volumn , Issue , 2012, Pages 197-223

  Strijack, Bradford ^a   Keown, Paul A ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Calcineurin; Concentration controlled therapy; Cyclophilin; Cyclosporine; Cytochrome P450; Immunosuppression; P glycoprotein; Sparse sampling; Therapeutic monitoring; Transplantation; Viral replication

Indexed keywords

EID: 84885762658     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781444355628.ch15     Document Type: Chapter

References (167)

1. Canadian Organ Replacement Register C. Annual Report: Treatment of end-stage organ failure in Canada 2000 to 2009. Ottawa, Ontario: Canadian Institute for Health Information;2010.
2. Australia and New Zealand Dialysis and Transplant Registry A. ANZDATA Registry Report 2010, Australia and New Zealand Dialysis and Transplant Registry, Adelaide, South Australia;2010.
3. United States Renal Data System. Annual Data Report 2010. Bethesda, MD;2010.
4. European Renal Association, European Dialysis and Transplant Association. ERA-EDTA Annual Report 2008. ERA-EDTA;2011.
5. Parasuraman R, Yee J, Karthikeyan V, del Busto R. Infectious complications in renal transplant recipients. Adv Chronic Kidney Dis 2006;13(3):280.
6. Keown P. Improving quality of life - the new target for transplantation. Transplantation 2001;72(12 Suppl):S67.
7. Yao G, Albon E, Adi Y et al. A systematic review and economic model of the clinical and cost-effectiveness of immunosuppressive therapy for renal transplantation in children. Health Technol Assess 2006;10(49):iii.
8. Winkelmayer WC, Weinstein MC, Mittleman MA et al. Health economic evaluations: the special case of end-stage renal disease treatment. Med Decis Making 2002;22(5):417.
9. Borel JF. History of the discovery of cyclosporin and of its early pharmacological development. Wien Klin Wochenschr 2002;114(12):433.
10. Keown PA, Essery-Rice G, Hellstrom A et al. Inhibition of human in vivo cytotoxic T lymphocyte generation by cyclosporine following organ transplantation. Transplantation 1985;40(1):45.
11. Galat A, Bua J. Molecular aspects of cyclophilins mediating therapeutic actions of their ligands. Cell Mol Life Sci 2010;67(20):3467.
12. Cai W, Hu L, Foulkes JG. Transcription-modulating drugs: mechanism and selectivity. Curr Opin Biotechnol 1996;7(6):608.
13. Stiller C. An overview of the first decade of cyclosporine. Transplant Proc 1996;28(4):2005.
14. Keown P, Stiller C, Ulan R et al. Immunological and pharmacological monitoring in the clinical use of cyclosporin A. Lancet 1981;1(8222):686.
15. Keown P. New concepts in cyclosporine monitoring. Curr Opin Nephrol Hypertens 2002;11(6):619.
16. Knoll G. Trends in kidney transplantation over the past decade. Drugs 2008;68(Suppl 1):3.
17. Gaston R. Current and evolving immunosuppressive regimens in kidney transplantation. Am J Kidney Dis 2006;47(4 Suppl 2):S3.
18. Kirk AD. Induction immunosuppression. Transplantation 2006;82(5):593.
19. Halloran P. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004;351(26):2715.
20. Wenger RM. Cyclosporine and analogues - isolation and synthesis - mechanism of action and structural requirements for pharmacological activity. Fortschr Chem Org Naturst 1986;50:123.
21. Lim E, Pon A, Djoumbou Y et al. T3DB: a comprehensively annotated database of common toxins and their targets. Nucleic Acids Res 2010;38(suppl 1):D781. http://www.t3db.org/toxins/T3D3498.
22. Lee J, Kim SS. An overview of cyclophilins in human cancers. J Int Med Res 2010;38(5):1561.
23. Le Hir M, Su Q, Weber L et al. In situ detection of cyclosporin A: evidence for nuclear localization of cyclosporine and cyclophilins. Lab Invest 1995;73(5):727.
24. Kim H, Kim WJ, Jeon ST et al. Cyclophilin A may contribute to the inflammatory processes in rheumatoid arthritis through induction of matrix degrading enzymes and inflammatory cytokines from macrophages. Clin Immunol 2005;116(3):217.
25. Wang L, Wang CH, Jia JF et al. Contribution of cyclophilin A to the regulation of inflammatory processes in rheumatoid arthritis. J Clin Immunol 2010;30(1):24.
26. Mascarell L, Truffa-Bachi P. New aspects of cyclosporin a mode of action: from gene silencing to gene up-regulation. Mini Rev Med Chem 2003;3(3):205.
27. Huai Q, Kim H-Y, Liu Y et al. Crystal structure of calcineurin-cyclophilin-cyclosporine shows common but distinct recognition of immunophilin-drug complexes. Proc Natl Acad Sci U S A 2002;99:12037.
28. Kiani A, Rao A, Aramburu J. Manipulating immune responses with immunosuppressive agents that target NFAT. Immunity 2000;12(4):359.
29. Cornell L, Smith R, Colvin R. Kidney transplantation: mechanisms of rejection and acceptance. Annu Rev Pathol 2008;3:189.
30. Datta A, David R, Glennie S et al. Differential effects of immunosuppressive drugs on T-cell motility. Am J Transplant 2006;6(12):2871.
31. Zhang C, Zhang J, Yang B, Wu C. Cyclosporin A inhibits the production of IL-17 by memory Th17 cells from healthy individuals and patients with rheumatoid arthritis. Cytokine 2008;42(3):345.
32. Wang H, Grzywacz B, Sukovich D et al. The unexpected effect of cyclosporin A on CD56-CD16 - and CD56 + CD16 + natural killer cell subpopulations. Blood 2007;110(5):1530.
33. Chen S, Zhao X, Tan J et al. Structure-based identification of small molecule compounds targeting cell cyclophilin A with anti-HIV-1 activity. Eur J Pharmacol 2007;565(1-3):54.
34. Satoh K, Shimokawa H, Berk BC. Cyclophilin A: promising new target in cardiovascular therapy. Circ J 2010;74(11):2249.
35. Saini M, Potash MJ. Novel activities of cyclophilin A and cyclosporin A during HIV-1 infection of primary lymphocytes and macrophages. J Immunol 2006;177(1):443.
36. Sokolskaja E, Olivari S, Zufferey M et al. Cyclosporine blocks incorporation of HIV-1 envelope glycoprotein into virions. J Virol 2010;84(9):4851.
37. Guichou JF, Viaud J, Mettling C et al. Structure-based design, synthesis, and biological evaluation of novel inhibitors of human cyclophilin A. J Med Chem 2006;49(3):900.
38. Pang X, Zhang M, Zhou L et al. Discovery of a potent peptidic cyclophilin A inhibitor Trp-Gly-Pro. Eur J Med Chem 2011;46(5):1701.
39. Ciesek S, Steinmann E, Wedemeyer H et al. Cyclosporine A inhibits hepatitis C virus nonstructural protein 2 through cyclophilin A. Hepatology 2009;50(5):1638.
40. Fischer G, Gallay P, Hopkins S. Cyclophilin inhibitors for the treatment of HCV infection. Curr Opin Investig Drugs 2010;11(8):911.
41. Kockx M, Jessup W, Kritharides L. Cyclosporin A and atherosclerosis - cellular pathways in atherogenesis. Pharmacol Ther 2010;128(1):106.
42. Kim SH, Lessner SM, Sakurai Y, Galis ZS. Cyclophilin A as a novel biphasic mediator of endothelial activation and dysfunction. Am J Pathol 2004;164(5):1567.
43. Jin ZG, Melaragno MG, Liao DF et al. Cyclophilin A is a secreted growth factor induced by oxidative stress. Circ Res 2000;87(9):789.
44. Beauchesne PR, Chung NS, Wasan KM. Cyclosporine A: a review of current oral and intravenous delivery systems. Drug Dev Ind Pharm 2007;33(3):211.
45. Keown P, Niese D. Cyclosporine microemulsion increases drug exposure and reduces acute rejection without incremental toxicity in de novo renal transplantation. International Sandimmun Neoral Study Group. Kidney Int 1998;54(3):938.
46. Helderman JH, Kang N, Legorreta AP, Chen JY. Healthcare costs in renal transplant recipients using branded versus generic ciclosporin. Appl Health Econ Health Policy 2010;8(1):61.
47. Johnston A, Belitsky P, Frei U et al. Potential clinical implications of substitution of generic cyclosporine formulations for cyclosporine microemulsion (Neoral) in transplant recipients. Eur J Clin Pharmacol 2004;60(6):389.
48. Czogalla A. Oral cyclosporine A - the current picture of its liposomal and other delivery systems. Cell Mol Biol Lett 2009;14(1):139.
49. Dunn CJ, Wagstaff AJ, Perry CM et al. Cyclosporin: an updated review of the pharmacokinetic properties, clinical efficacy and tolerability of a microemulsionbased formulation (Neoral®) in organ transplantation. Drugs 2001;61(13):1957.
50. Kelly P, Kahan BD. Review: metabolism of immunosuppressant drugs. Curr Drug Metab 2002;3(3):275.
51. Masuda S, Inui K. An up-date review on individualized dosage adjustment of calcineurin inhibitors in organ transplant patients. Pharmacol Ther 2006;112(1):184.
52. Thervet E, Anglicheau D, Legendre C, Beaune P. Role of pharmacogenetics of immunosuppressive drugs in organ transplantation. Ther Drug Monit 2008;30(2):143.
53. Thervet E, Legendre C, Beaune P, Anglicheau D. Cytochrome P450 3A polymorphisms and immunosuppressive drugs. Pharmacogenomics 2005;6(1):37.
54. Hu YF, Qiu W, Liu ZQ et al. Effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine pharmacokinetics after renal transplantation. Clin Exp Pharmacol Physiol 2006;33(11):1093.
55. Demeule M, Laplante A, Sepehr-Araé A et al. Inhibition of P-glycoprotein by cyclosporin A analogues and metabolites. Biochem Cell Biol 1999;77(1):47.
56. Mourad M, Wallemacq P, De Meyer M et al. Biotransformation enzymes and drug transporters pharmacogenetics in relation to immunosuppressive drugs: impact on pharmacokinetics and clinical outcome. Transplantation 2008;85(7 Suppl):S19.
57. Kuypers DR. Influence of interactions between immunosuppressive drugs on therapeutic drug monitoring. Ann Transplant 2008;13(3):11.
58. Pal D, Mitra AK. MDR- and CYP3A4-mediated drugdrug interactions. J Neuroimmune Pharmacol 2006;1(3):323.
59. Lam S, Partovi N, Ting L, Ensom M. Corticosteroid interactions with cyclosporine, tacrolimus, mycophenolate, and sirolimus: fact or fiction? Ann Pharmacother 2008;42(7):1037.
60. Kuypers DR, Ekberg H, Grinyó J et al. Mycophenolic acid exposure after administration of mycophenolate mofetil in the presence and absence of cyclosporin in renal transplant recipients. Clin Pharmacokinet 2009;48(5):329.
61. Asberg A, Hartmann A, Fjeldså E et al. Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients. Am J Transplant 2001;1(4):382.
62. Bai S, Stepkowski S, Kahan B, Brunner L. Metabolic interaction between cyclosporine and sirolimus. Transplantation 2004;77(10):1507.
63. Podder H, Stepkowski SM, Napoli KL et al. Pharmacokinetic interactions augment toxicities of sirolimus/cyclosporine combinations. J Am Soc Nephrol 2001;12(5):1059.
64. Wrishko RE, Levine M, Primmett DR et al. Investigation of a possible interaction between ciprofloxacin and cyclosporine in renal transplant patients. Transplantation 1997;64(7):996.
65. Williamson EM. Drug interactions between herbal and prescription medicines. Drug Saf 2003;26(15):1075.
66. Taylor PJ, Tai CH, Franklin ME, Pillans PI. The current role of liquid chromatography-tandem mass spectrometry in therapeutic drug monitoring of immunosuppressant and antiretroviral drugs. Clin Biochem 2011;44(1):14.
67. Mendonza A, Gohh R, Akhlaghi F. Determination of cyclosporine in saliva using liquid chromatography- tandem mass spectrometry. Ther Drug Monit 2004;26(5):569.
68. Kahan B, Keown P, Levy G, Johnston A. Therapeutic drug monitoring of immunosuppressant drugs in clinical practice. Clin Ther 2002;24(3):330.
69. Morris RG, Holt DW, Armstrong VW et al. Analytic aspects of cyclosporine monitoring, on behalf of the IFCC/IATDMCT Joint Working Group. Ther Drug Monit 2004;26(2):227.
70. Wallemacq PE. Therapeutic monitoring of immunosuppressant drugs. Where are we? Clin Chem Lab Med 2004;42(11):1204.
71. Soldin SJ, Hardy RW, Wians FH et al. Performance evaluation of the new ADVIA Centaur system cyclosporine assay (single-step extraction). Clin Chim Acta 2010;411(11-12):806.
72. Steimer W. Performance and specificity of monoclonal immunoassays for cyclosporine monitoring: how specific is specific? Clin Chem 1999;45(3):371.
73. Fernández-Marmiesse A, Hermida J, Tutor JC. Comparison of predose vs 2-h postdose blood metabolites/cyclosporine ratios in kidney and liver transplant patients. Clin Biochem 2000;33(5):383.
74. Garrido MJ, Hermida J, Tutor JC. Relationship between cyclosporine concentrations obtained using the Roche Cobas Integra and Abbott TDx monoclonal immunoassays in pre-dose and two hour post-dose blood samples from kidney transplant recipients. Ther Drug Monit 2002;24(6):785.
75. Morris RG. Cyclosporin therapeutic drug monitoring - an established service revisited. Clin Biochem Rev 2003;24(2):33.
76. Debord J, Risco E, Harel M et al Application of a gamma model of absorption to oral cyclosporin. Clin Pharmacokinet 2001;40(5):375.
77. Leger F, Debord J, Le Meur Y et al Maximum a posteriori Bayesian estimation of oral cyclosporin pharmacokinetics in patients with stable renal transplants. Clin Pharmacokinet 2002;41(1):71.
78. International Neoral Renal Transplant Study Group. Cyclosporine microemulsion (Neoral) absorption profiling and sparse-sample predictors during the first 3 months after renal transplantation. Am J Transplant 2002;2(2):148.
79. Canadian Neoral Renal Transplant Study Group. Absorption profiling of cyclosporine microemulsion (neoral) during the first 2 weeks after renal transplantation. Transplantation 2001;72(6):1024.
80. Primmett DR, Levine M, Kovarik JM et al. Cyclosporine monitoring in patients with renal transplants: two- or three-point methods that estimate area under the curve are superior to trough levels in predicting drug exposure. Ther Drug Monit 1998;20(3):276.
81. David O, Johnston A. Limited sampling strategies. Clin Pharmacokinet 2000;39(4):311.
82. David OJ, Johnston A. Limited sampling strategies for estimating cyclosporin area under the concentration- time curve: review of current algorithms. Ther Drug Monit 2001;23(2):100.
83. Monchaud C, Rousseau A, Leger F et al. Limited sampling strategies using Bayesian estimation or multilinear regression for cyclosporin AUC(0-12) monitoring in cardiac transplant recipients over the first year post-transplantation. Eur J Clin Pharmacol 2003;58(12):813.
84. Rousseau A, Monchaud C, Debord J et al. Bayesian forecasting of oral cyclosporin pharmacokinetics in stable lung transplant recipients with and without cystic fibrosis. Ther Drug Monit 2003;25(1):28.
85. Meier-Kriesche HU, Kaplan B, Brannan P et al. A limited sampling strategy for the estimation of eighthour neoral areas under the curve in renal transplantation. Ther Drug Monit 1998;20(4):401.
86. Meier-Kriesche HU, Alloway R, Gaber AO et al. A limited sampling strategy for the estimation of 12-hour SangCya and neoral AUCs in renal transplant recipients. J Clin Pharmacol 1999;39(2):166.
87. Clase C, Mahalati K, Kiberd B et al. Adequate early cyclosporin exposure is critical to prevent renal allograft rejection: patients monitored by absorption profiling. Am J Transplant 2002;2(8):789.
88. Press RR, de Fijter JW, Guchelaar HJ. Individualizing calcineurin inhibitor therapy in renal transplantation - current limitations and perspectives. Curr Pharm Des 2010;16(2):176.
89. The Canadian Multicentre Transplant Study Group. A randomized clinical trial of cyclosporine in cadaveric renal transplantation. Analysis at three years. N Engl J Med 1986;314(19):1219.
90. Merion RM, White DJ, Thiru S et al. Cyclosporine: five years'experience in cadaveric renal transplantation. N Engl J Med 1984;310(3):148.
91. A randomized clinical trial of cyclosporine in cadaveric renal transplantation. N Engl J Med 1983;309(14):809.
92. Pollard SG, Lear PA, Ready AR et al. Comparison of microemulsion and conventional formulations of cyclosporine A in preventing acute rejection in de novo kidney transplant patients. The U.K. Neoral Renal Study Group. Transplantation 1999;68(9):1325.
93. Levy GA. Neoral use in the liver transplant recipient. Transplant Proc 2000;32(3A Suppl):2 S.
94. Mahalati K, Belitsky P, Sketris I et al. Neoral monitoring by simplified sparse sampling area under the concentration-time curve: its relationship to acute rejection and cyclosporine nephrotoxicity early after kidney transplantation. Transplantation 1999;68(1):55.
95. Internation Neoral Renal Transplantation Study Group. Randomized, international study of cyclosporine microemulsion absorption profiling in renal transplantation with basiliximab immunoprophylaxis. Am J Transplant 2002;2(2):157.
96. Cantarovich M, Besner JG, Barkun JS et al. Two-hour cyclosporine level determination is the appropriate tool to monitor Neoral therapy. Clin Transplant 1998;12(3):243.
97. Oellerich M, Armstrong VW. Two-hour cyclosporine concentration determination: an appropriate tool to monitor neoral therapy? Ther Drug Monit 2002;24(1):40.
98. Glanville AR, Morton JM, Aboyoun CL et al. Cyclosporine C 2 monitoring improves renal dysfunction after lung transplantation. J Heart Lung Transplant 2004;23(10):1170.
99. Morton JM, Aboyoun CL, Malouf MA et al. Enhanced clinical utility of de novo cyclosporine C 2 monitoring after lung transplantation. J Heart Lung Transplant 2004;23(9):1035.
100. Delgado DH, Rao V, Hamel J et al. Monitoring of cyclosporine 2-hour post-dose levels in heart transplantation: improvement in clinical outcomes. J Heart Lung Transplant 2005;24(9):1343.
101. Mathias HC, Ozalp F, Will MB et al. A randomized, controlled trial of C 0 - vs C 2 -guided therapeutic drug monitoring of cyclosporine in stable heart transplant patients. J Heart Lung Transplant 2005;24(12):2137.
102. Pescovitz MD, Barbeito R , Simulect US01 Study Group. Two-hour post-dose cyclosporine level is a better predictor than trough level of acute rejection of renal allografts. Clin Transplant 2002;16(5):378.
103. 2 monitoring of cyclosporine microemulsion. Transplantation 2003;76(6):903.
104. 2 monitoring in long-term renal transplant recipients receiving cyclosporine microemulsion. Transplantation 2005;79(7):802.
105. 2 monitoring in the long-term management of renal transplant recipients. Transplantation 2003;75(12):2086.
106. 2 monitoring of cyclosporine a microemulsion: results of a 12-month, randomized, multicenter study. Transplantation 2005;79(5):577.
107. David-Neto E, Lemos FB, Furusawa EA et al. Impact of cyclosporin A pharmacokinetics on the presence of side effects in pediatric renal transplantation. J Am Soc Nephrol 2000;11(2):343.
108. 2 -monitoring over three years in maintenance heart transplantation. Swiss Med Wkly 2011;141: w13149.
109. U.S. Renal Data System U. Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases;2006.
110. Meier-Kriesche HU, Li S, Gruessner RW et al. Immunosuppression: evolution in practice and trends, 1994-2004. Am J Transplant 2006;6(5 Pt 2):1111.
111. Pirsch JD, Miller J, Deierhoi MH et al. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. Transplantation 1997;63(7):977 [see comment].
112. Mayer AD, Dmitrewski J, Squifflet JP 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. Transplantation 1997;64(3):436.
113. Margreiter R, European Tacrolimus vs Ciclosporin Microemulsion Renal Transplantation Study Group. Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. Lancet 2002;359(9308):741.
114. Krämer BK, Del Castillo D, Margreiter R et al. Efficacy and safety of tacrolimus compared with ciclosporin A in renal transplantation: three-year observational results. Nephrol Dial Transplant 2008;23(7):2386.
115. Tanabe K. Calcineurin inhibitors in renal transplantation: what is the best option? Drugs 2003;63(15):1535.
116. Johnson C, Ahsan N, Gonwa T et al. Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation. Transplantation 2000;69(5):834.
117. Ahsan N, Johnson C, Gonwa T 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 years. Transplantation 2001;72(2):245.
118. Gonwa T, Johnson C, Ahsan N et al. Randomized trial of tacrolimus + mycophenolate mofetil or azathioprine versus cyclosporine + mycophenolate mofetil after cadaveric kidney transplantation: results at three years. Transplantation 2003;75(12):2048.
119. Heisel O, Heisel R, Balshaw R, Keown P. New onset diabetes mellitus in patients receiving calcineurin inhibitors: a systematic review and meta-analysis. Am J Transplant 2004;4(4):583.
120. Montagnino G, Tarantino A, Segoloni GP et al. Longterm results of a randomized study comparing three immunosuppressive schedules with cyclosporine in cadaveric kidney transplantation. J Am Soc Nephrol 2001;12(10):2163.
121. Pascual J, Galeano C, Royuela A, Zamora J. A systematic review on steroid withdrawal between 3 and 6 months after kidney transplantation. Transplantation 2010;90(4):343.
122. Barraclough K, Landsberg D, Shapiro R et al. A matched cohort pharmacoepidemiological analysis of steroid free immunosuppression in renal transplantation. Transplantation 2009;87(5):672.
123. Vincenti F, Schena FP, Paraskevas S et al. A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients. Am J Transplant 2008;8(2):307.
124. Mukherjee S, Mukherjee U. A comprehensive review of immunosuppression used for liver transplantation. J Transplant 2009;2009:701464.
125. O'Grady JG, Burroughs A, Hardy P et al. Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial. Lancet 2002;360(9340):1119.
126. O'Grady JG, Hardy P, Burroughs AK et al. Randomized controlled trial of tacrolimus versus microemulsified cyclosporin (TMC) in liver transplantation: poststudy surveillance to 3 years. Am J Transplant 2007;7(1):137.
127. McAlister VC, Haddad E, Renouf E et al. Cyclosporin versus tacrolimus as primary immunosuppressant after liver transplantation: a meta-analysis. Am J Transplant 2006;6(7):1578.
128. Haddad EM, McAlister VC, Renouf E et al. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst Rev 2006;(4):CD005161.
129. Henry SD, Metselaar HJ, Lonsdale RC et al. Mycophenolic acid inhibits hepatitis C virus replication and acts in synergy with cyclosporin A and interferon-alpha. Gastroenterology 2006;131(5):1452.
130. Firpi RJ, Zhu H, Morelli G et al. Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation. Liver Transpl 2006;12(1):51.
131. Berenguer M, Royuela A, Zamora J. Immunosuppression with calcineurin inhibitors with respect to the outcome of HCV recurrence after liver transplantation: results of a meta-analysis. Liver Transpl 2007;13(1):21.
132. Heaphy MR, Shamma HN, Hickmann M, White MJ. Cyclosporine-induced folliculodystrophy. J Am Acad Dermatol 2004;50(2):310.
133. Takahashi T, Kamimura A. Cyclosporin a promotes hair epithelial cell proliferation and modulates protein kinase C expression and translocation in hair epithelial cells. J Invest Dermatol 2001;117(3):605.
134. Ho YC, Lin HJ, Tsai CH, Chang YC. Regulation of type I plasminogen activator inhibitor in human gingival fibroblasts with cyclosporine A. Oral Dis 2010;16(4):396.
135. Tamilselvan S, Raju SN, Loganathan D et al. Endothelin-1 and its receptors ET A and ET B in druginduced gingival overgrowth. J Periodontol 2007;78(2):290.
136. Grassi FR, Pappalardo S, Baglìo OA et al. Gingival overgrowth in renal transplant recipients induced by pharmacological treatment. Review of the literature. Minerva Stomatol 2006;55(1-2):59.
137. Lucas VS, Roberts GJ. Oro-dental health in children with chronic renal failure and after renal transplantation: a clinical review. Pediatr Nephrol 2005;20(10):1388.
138. Niles DG, Rynearson RD, Baum M et al. A study of craniofacial growth in infant heart transplant recipients receiving cyclosporine. J Heart Lung Transplant 2000;19(3):231.
139. Sprague SM. Mechanism of transplantation-associated bone loss. Pediatr Nephrol 2000;14(7):650.
140. Cunningham J. Posttransplantation bone disease. Transplantation 2005;79(6):629.
141. Cohen A, Addonizio LJ, Softness B et al. Growth and skeletal maturation after pediatric cardiac transplantation. Pediatr Transplant 2004;8(2):126.
142. Woo JT, Yonezawa T, Cha BY et al. Pharmacological topics of bone metabolism: antiresorptive microbial compounds that inhibit osteoclast differentiation, function, and survival. J Pharmacol Sci 2008;106(4):547.
143. Tamler R, Epstein S. Nonsteroid immune modulators and bone disease. Ann N Y Acad Sci 2006;1068:284.
144. Ponticelli C, Campise MR. Neurological complications in kidney transplant recipients. J Nephrol 2005;18(5):521.
145. Saner FH, Gensicke J, Olde Damink SW et al. Neurologic complications in adult living donor liver transplant patients: an underestimated factor? J Neurol 2010;257(2):253.
146. Yardimci N, Colak T, Sevmis S et al. Neurologic complications after renal transplant. Exp Clin Transplant 2008;6(3):224.
147. Maggioni F, Mantovan MC, Rigotti P et al. Headache in kidney transplantation. J Headache Pain 2009;10(6):455.
148. Ishikura K, Ikeda M, Hamasaki Y et al. Posterior reversible encephalopathy syndrome in children: its high prevalence and more extensive imaging findings. Am J Kidney Dis 2006;48(2):231.
149. Uoshima N, Karasuno T, Yagi T et al. Late onset cyclosporine-induced cerebral blindness with abnormal SPECT imagings in a patient undergoing unrelated bone marrow transplantation. Bone Marrow Transplant 2000;26:105.
150. Bouvier N, Flinois JP, Gilleron J et al. Cyclosporine triggers endoplasmic reticulum stress in endothelial cells: a role for endothelial phenotypic changes and death. Am J Physiol Renal Physiol 2009;296(1):F160.
151. Al-Massarani G, Vacher-Coponat H, Paul P et al. Impact of immunosuppressive treatment on endothelial biomarkers after kidney transplantation. Am J Transplant 2008;8(11):2360.
152. Nickel T, Schlichting CL, Weis M. Drugs modulating endothelial function after transplantation. Transplantation 2006;82(1 Suppl):S41.
153. Tomasiak M, Rusak T, Gacko M, Stelmach H. Cyclosporine enhances platelet procoagulant activity. Nephrol Dial Transplant 2007;22(6):1750.
154. Mangray M, Vella JP. Hypertension after kidney transplant. Am J Kidney Dis 2011;57(2):331.
155. Koomans HA, Ligtenberg G. Mechanisms and consequences of arterial hypertension after renal transplantation. Transplantation 2001;72(6 Suppl):S9.
156. Bouhaddi M, Delbosc B, Fortrat JO et al. Six-month cardiovascular changes in cyclosporine-treated recipients of corneal grafts: serial baroreflex responses. Transpl Int 2004;17(6):325.
157. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009;4(2):481.
158. Petric R, Freeman D, Wallace C et al. Effect of cyclosporine on urinary prostanoid excretion, renal blood flow, and glomerulotubular function. Transplantation 1988;45(5):883.
159. Burdmann EA, Andoh TF, Yu L, Bennett WM. Cyclosporine nephrotoxicity. Semin Nephrol 2003;23(5):465.
160. Bobadilla NA, Gamba G. New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone. Am J Physiol Renal Physiol 2007;293(1):F2.
161. Petric R, Freeman D, Wallace C et al. Modulation of experimental cyclosporine nephrotoxicity by inhibition of thromboxane synthesis. Transplantation 1990;50(4):558.
162. Zhong Z, Arteel GE, Connor HD et al. Cyclosporin A increases hypoxia and free radical production in rat kidneys: prevention by dietary glycine. Am J Physiol 1998;275(4 Pt 2):F595.
163. Longoni B, Boschi E, Demontis GC et al. 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(3):731.
164. Abbott KC, Kimmel PL, Dharnidharka V et al. Newonset gout after kidney transplantation: incidence, risk factors and implications. Transplantation 2005;80(10):1383.
165. Wilkinson A, Davidson J, Dotta F et al. Guidelines for the treatment and management of new-onset diabetes after transplantation. Clin Transplant 2005;19(3):291.
166. Hjelmesaeth J, Asberg A, Müller F et al. New-onset posttransplantation diabetes mellitus: insulin resistance or insulinopenia? Impact of immunosuppressive drugs, cytomegalovirus and hepatitis C virus infection. Curr Diabetes Rev 2005;1(1):1.
167. Mathis AS, Davé N, Knipp GT, Friedman GS. Drugrelated dyslipidemia after renal transplantation. Am J Health Syst Pharm 2004;61(6):565.