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The metabolic effects of cyclosporin and tacrolimus

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Abstract

The introduction of cyclosporin and, more recently, tacrolimus in the immunosuppression of transplanted patients has lead to prolonged graft survival and increased patients’ life expectancy. It has been therefore possible to evaluate the effects of long-term treatment with these drugs and metabolic alterations in patients on cyclosporin or tacrolimus have been reported by several authors. In particular, the use of these drugs is associated with abnormalities of glucose and lipid metabolism. Post-transplant diabetes is more common with tacrolimus, probably due to more marked effects on the pancreatic beta-cells, whereas increased levels of cholesterol and triglycerides are more frequently associated with cyclosporin treatment, even though, in this latter case, steroid treatment seems to play a major role. Comparison and intervention studies must be planned to evaluate the best therapeutical approaches to control these abnormalities and to assess the possibility to further increase graft and patient survival by appropriate treatment of diabetes and hyperlipidemia.

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References

  1. Noble S., Markham A. Cyclosporin: a review of the pharmacokinetic properties, clinical efficacy and tolerability of a microemulsion-based formulation. Drugs 1995, 50: 924–941.

    Article  CAS  PubMed  Google Scholar 

  2. Spencer C.M., Goa K.L., Gillis J.C. Tacrolimus: an update of its pharmacology and clinical efficacy in the management of organ transplantation. Drugs 1997, 54: 925–975.

    Article  CAS  PubMed  Google Scholar 

  3. Jindal R.M., Sidner R.A., Milgrom M.L. Post-transplant diabetes mellitus. The role of immunosuppression. Drug Saf. 1997, 16: 242–257.

    Article  CAS  PubMed  Google Scholar 

  4. Jain A., Khanna A., Molmenti E.P., Rishi N., Fung J.J. Immunosuppressive therapy. Surg. Clin. North Am. 1999, 79: 59–76.

    Article  CAS  PubMed  Google Scholar 

  5. Miles A.M., Sumrani N., Horowitz R., Homel P., Maursky V., Markell M.S., Distant D.A., Hong J.H., Sommer B.G., Friedman E.A. Diabetes mellitus after renal transplantation: as deleterious as non-transplant-associated diabetes? Transplantation 1998, 65: 380–384.

    Article  CAS  PubMed  Google Scholar 

  6. Neylan J.F. Racial differences in renal transplantation after immunosuppression with tacrolimus versus cyclosporine. FK506 Kidney Transplant Study Group. Transplantation 1998, 65: 515–523.

    Article  CAS  PubMed  Google Scholar 

  7. Markell M.S., Armenti V., Danovitch G., Sumrani N. Hyperlipidemia and glucose intolerances in the postrenal transplant patient. J. Am. Soc. Nephrol. 1994, 4: S37–S47.

    CAS  PubMed  Google Scholar 

  8. Pirsch J.D., Miller J., Deierhoi M.H., Vincenti F., Filo R.S. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group. Transplantation 1997, 63: 977–983.

    Article  CAS  PubMed  Google Scholar 

  9. Krentz A.J., Dousset B., Mayer D., McMaste P., Buckels J., Cramb R., Smith J.M., Nattrass M. Metabolic effects of cyclosporin A and FK506 in liver transplant recipients. Diabetes 1993, 42: 1753–1759.

    Article  CAS  PubMed  Google Scholar 

  10. Mayer A.D., Dmitrewski J., Squifflet J.P., Besse T., Grabensee B., Klein B., Eigler F.W., Heeman U., Pichlmayr R. Multicenter randomized trial comparing tacrolimus and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation 1997, 64: 436–443.

    Article  CAS  PubMed  Google Scholar 

  11. Cavaille-Coll M.W., Elashoff M.R. Commentary on a comparison of tacrolimus and cyclosporine for immunosuppression after cadaveric renal transplantation. Transplantation 1998, 65: 142–143.

    Article  CAS  PubMed  Google Scholar 

  12. Saudek F., Pelikanova T., Bartos V., Reneltova I., Kazdova L., Kovar J., Karasova L. Insulin action and insulin binding following pancreas transplantation. Diabetologia 1991, 34 (Suppl. 1): 71–75.

    Article  Google Scholar 

  13. Berwerck S., Kahl A., Bechstein W., Platz K., Muller U., Neuhaus P., Frei U. Clinical use of the euglycemic hyperinsulinemic clamp for diagnosis of tacrolimus-induced insulin resistance after combined pancreas-kidney transplantation. Transplant. Proc. 1998, 30: 1944–1945.

    Article  Google Scholar 

  14. Menegazzo L.A., Ursich M.J., Fukui R.T., Rocha D.M., Silva M.E., Ianhez L.E., Sabbaga E., Wajchenberg B.L. Horm. Metab. Res. 1998, 30: 663–667.

    Article  CAS  PubMed  Google Scholar 

  15. Basadonna G., Montorsi F., Dakizaki K., Merrell R.C. Cyclosporin A and islet function. Am. J. Surg. 1988, 156: 191–193.

    Article  CAS  PubMed  Google Scholar 

  16. Bani-Sacchi T., Bani D., Filipponi F., Michel A., Houssin D. Immunocytochemical and ultrastructural changes of islet cells in rats treated long-term with cyclosporine at immunotherapeutic doses. Transplantation 1990, 49: 982–987.

    Article  CAS  PubMed  Google Scholar 

  17. Nielsen J.H., Mandrup-Poulsen T., Nerup J. Direct effects of cyclosporine A on human pancreatic beta-cells. Diabetes 1986, 35: 1049–1052.

    Article  CAS  PubMed  Google Scholar 

  18. Wahlstrom H.E., Akimoto R., Endres D., Kolterman O., Moossa A.R. Recovery and hypersecretion of insulin and reversal of insulin resistance after withdrawal of short-term cyclosporine treatment. Transplantation 1992, 53: 1190–1195.

    Article  CAS  PubMed  Google Scholar 

  19. Martin F., Bedoya F.J. Mechanisms of action of cyclosporin A on islet alpha-and beta-cells. Effects on cAMP and calciumdependent pathways. Life Sci. 1991, 49: 1915–1921.

    Article  CAS  PubMed  Google Scholar 

  20. Marchetti P., Kneteman N.M., Swanson C.J., Olack B.J., Scharp D.W. Effect of cyclosporin treatment on metabolic and hormonal responses to mixed meal plus oral glucose in dogs with intrasplenic pancreatic islet autograft. Res. Exp. Med. 1994, 194: 45–52.

    Article  CAS  Google Scholar 

  21. Kneteman N.M., Marchetti P., Tordjman K., Bier D.M., Santiago J.V., Swanson C.J., Olack B.J., Scharp D.W. Effects of cyclosporine on insulin secretion and insulin sensitivity in dogs with intrasplenic islet autotransplants. Surgery 1992, 111: 430–437.

    CAS  PubMed  Google Scholar 

  22. Alejandro R., Feldman E.C., Bloom A.D., Kenyon N.S. Effects of cyclosporin on insulin and C-peptide secretion in healthy beagles. Diabetes 1989, 38: 698–703.

    Article  CAS  PubMed  Google Scholar 

  23. Hirano Y., Fujihira S., Ohara K., Katsuki S., Noguchi H. Morphological and functional changes of islets of Langerhans in FK506-treated rats. Transplantation 1992, 53: 889–894.

    Article  CAS  PubMed  Google Scholar 

  24. Redmon J.B., Olson L.K., Armstrong M.B., Greene M.J., Robertson R.P. Effects of tacrolimus (FK506) on human insulin gene expression, insulin mRNA levels, and insulin secretion in HIT-T15 cells. J. Clin. Invest. 1996, 98: 2786–2793.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Tze W.J., Tai J., Cheung S. In vitro effects of FK506 on human and rat islets. Transplantation 1990, 49: 1172–1174.

    Article  CAS  PubMed  Google Scholar 

  26. Ishizuka J., Gugliuzza K.K., Wassmuth Z., Hsieh J., Sato K., Tsuchiya T., Towsend C.M. Jr., Fish J.C., Thompson J.C. Effects of FK506 and cyclosporine on dynamic insulin secretion from isolated dog pancreatic islets. Transplantation 1993, 56: 1486–1490.

    Article  CAS  PubMed  Google Scholar 

  27. Noguchi N., Takasawa S., Nata K., Tohgo A., Kato I., Ikehata F., Yonekura H., Okamoto H. Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsome. J. Biol. Chem. 1997, 272: 3133–3136.

    Article  CAS  PubMed  Google Scholar 

  28. Marchetti P., Giannarelli R., Di Carlo A., Navalesi R. Pharmacokinetic optimization of oral hypoglycaemic therapy. Clin. Pharmacokin. 1991, 21: 308–317.

    Article  CAS  Google Scholar 

  29. Chidster P.D., Connito D.J. Interaction between glipizide and cyclosporine: report of two cases. Transplant Proc. 1993, 25: 2136–2137.

    Google Scholar 

  30. Sagedal S., Asberg A., Hartmann A., Bergan S., Berg K.J. Glipizide treatment of post-transplant diabetes does not interfere with cyclosporine pharmacokinetics in renal allograft recipients. Clin. Transplant. 1998, 12: 553–556.

    CAS  PubMed  Google Scholar 

  31. Islam S.I., Masuda Q.N., Bolaji O.O., Shaheen F.M., Sheikh I.A. Possible interaction between cyclosporine and glibenclamide in posttransplant diabetic patients. Ther. Drug Monit. 1996, 18: 624–626.

    Article  CAS  PubMed  Google Scholar 

  32. Park M.H., Pelegrin D., Haug M.T., Young J.B. Troglitazone, a new antidiabetic agent, decreases cyclosporine level. J. Heart Lung Transplant. 1998, 17: 1139–1140.

    CAS  PubMed  Google Scholar 

  33. Maffi P, Bertuzzi F, Aldrighetti L, Taglietti MV, Castelnuovo A, Pozza G, Di Carlo V, Secchi A. Role of metformin on islet engraftment after transplantation in humans. Diabetologia 1999, 42 (Suppl. 1): A33.

    Google Scholar 

  34. Lupi R., Del Guerra S., Tellini C., Giannarelli R., Coppelli A., Lorenzetti M., Carmellini M., Mosca F., Navalesi R., Marchetti P. The biguanide compound metformin prevents desensitization of human pancreatic islets induced by high glucose. Eur. J. Pharmacol. 1999, 364: 205–209.

    Article  CAS  PubMed  Google Scholar 

  35. Schorn T.F., Kliem V., Bojanovski M., Bojanowski D., Repp H., Bunzendahl H., Frei U. Impact of long-term immunosuppression with cyclosporin A on serum lipids in stable renal transplant recipients. Transpl. Int. 1991, 4: 92–95.

    Article  CAS  PubMed  Google Scholar 

  36. Aakhus S., Dahl K., Wideroe T.E. Hyperlipemia in renal transplant patients. J. Intern. Med. 1996, 239: 407–415.

    Article  CAS  PubMed  Google Scholar 

  37. von Ahsen N., Helmhold M., Schutz E., Eisenhauer T., Armstrong V.W., Oellerich M. Cyclosporin A trough levels correlate with serum lipoproteins and apolipoproteins: implications for therapeutic drug monitoring of cyclosporin A. Ther. Drug Monit. 1997, 19: 140–145.

    Article  Google Scholar 

  38. Jain A.B., Kashyap R., Rakela J., Starzl T.E., Fung J.J. Primary adult liver transplantation under tacrolimus: more than 90 months actual follow-up survival and adverse events. Liver Transpl. Surg. 1999, 5: 144–150.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Asante-Korang A., Boyle G.J., Webber S.A., Miller S.A., Fricker F.J. Experience of FK506 immunosuppression in pedriatic heart transplantation: a study of long-term adverse effects. J. Heart Lung Transplant. 1996, 15: 415–422.

    CAS  PubMed  Google Scholar 

  40. Hohage H., Arlt M., Bruckner D., Dielt K.H., Zidek W., Spieker C. Effects of cyclosporin A and FK 506 on lipid metabolism and fibrinogen in kidney transplant recipients. Clin. Transplant. 1997, 11: 225–230.

    Google Scholar 

  41. Canzanello V.J., Schwartz L., Taler S.J., Textor S.C., Wiesner R.H., Porayko M.K., Krom R.A. Evolution of cardiovascular risk after liver transplantation: a comparison of cyclosporine A and tacrolimus (FK506). Liver Transpl. Surg. 1997, 3: 1–9.

    Article  CAS  PubMed  Google Scholar 

  42. Satterthwaite R., Aswad S., Sunga V., Shidban H., Bogard T., Asai P., Khetan U., Akra I., Mendez R.G., Mendez R. Incidence of new-onset hypercholesterolemia in renal transplant patients treated with FK506 or cyclosporine. Transplantation 1998, 65: 446–449.

    Article  CAS  PubMed  Google Scholar 

  43. Pratschke J., Neuhaus R., Tullius S.G., Haller G.W., Jonas S., Steinmueller T., Bechstein W.O., Neuhaus P. Treatment of cyclosporine-related adverse effects by conversion to tacrolimus after liver transplantation. Transplantation 1997, 64: 938–940.

    Article  CAS  PubMed  Google Scholar 

  44. de Sevaux R.G., Hilbrands L.B., Tiggeler R.G., Koene R.A., Hoitsma A.J. A randomised, prospective study on the conversion from cyclosporine-prednisone to cyclosporine-azathioprine at 6 months after renal transplantation. Transpl. Int. 1998, 11 (Suppl. 1): 322–324.

    Article  Google Scholar 

  45. Hollander A.A., Hene R.J., Hermans J., Van Es L.A., van der Woude F.J. Late prednisone withdrawal in cyclosporine-treated kidney transplant patients: a randomized study. J. Am. Soc. Nephrol. 1997, 8: 294–301.

    CAS  PubMed  Google Scholar 

  46. Ingulli E., Tejani A., Markell M. The beneficial effects of steroid withdrawal on blood pressure and lipid profile in children posttransplantation in the cyclosporine era. Transplantation 1993, 55: 1029–1033.

    Article  CAS  PubMed  Google Scholar 

  47. Stegall M.D., Everson G.T., Schroter G., Karrer F., Bilir B., Sternberg T., Shrestha R., Wachs M., Kam I. Prednisone withdrawal late after adult liver transplantation reduces diabetes, hypertension, and hypercholesterolemia without causing graft loss. Hepatology 1997, 25: 173–177.

    Article  CAS  PubMed  Google Scholar 

  48. Ferraris J.R., Sorroche P., Legal S., Oyhamburu J., Brandi P., Pasqualini T. Effect of therapy with deflazacort on dyslipoproteinemia after pediatric renal transplantation. J. Pediatr. 1998, 133: 533–536.

    Article  CAS  PubMed  Google Scholar 

  49. Dunn T.B., Asolati M., Holman D.M., Raofi V., Jovanovic B., Pollak R., Benedetti E. Long-term outcome of a prospective trial of steroid withdrawal after kidney transplantation. Surgery 1999, 125: 155–159.

    Article  CAS  PubMed  Google Scholar 

  50. Chan F.K., Shaffer E.A. Cholestatic effects of cyclosporine in the rat. Transplantation 1997, 63: 1574–1578.

    Article  CAS  PubMed  Google Scholar 

  51. Theilmann L., Otto G., Arnold J., Gmelin K., Stiehl A. Biliary secretion of bile acids, lipids, and bilirubin by the transplanted liver. A quantitative study in patients on cyclosporine. Transplantation 1991, 52: 1020–1023.

    Article  CAS  PubMed  Google Scholar 

  52. Winegar D.A., Salisbury J.A., Sundseth S.S., Hawke R.L. Effects of cyclosporin on cholesterol 27-hydroxylation and LDL receptor activity in HepG2 cells. J. Lipid. Res. 1996, 37: 179–191.

    CAS  PubMed  Google Scholar 

  53. Kaptein A., De Wit E.C., Princen H.M. Cotranslational inhibition of apoB-100 synthesis by cyclosporin A in the human hepatoma cell line HepG2. Arterioscler. Thromb. 1994, 14: 780–789.

    Article  CAS  PubMed  Google Scholar 

  54. Derfler K., Hayde M., Heinz G., Hirschl M.M., Steger G., Hauser A.C., Balcker P., Widhalm K. Decreased postheparin lipolytic activity in renal transplant recipients with cyclosporin A. Kidney Int. 1991, 40: 720–727.

    Article  CAS  PubMed  Google Scholar 

  55. Arnadottir M., Thysell H., Nilsson-Ehle P. Lipoprotein levels and post-heparin lipase activities in kidney transplant recipients: ciclosporin-vs nonciclosporin-treated patients. Am. J. Nephrol. 1991, 11: 391–396.

    Article  CAS  PubMed  Google Scholar 

  56. Libby P. Transplantation-associated arteriosclerosis: potential mechanisms. In: Transplantation Biology: Cellular and Molecular Aspects, Lippincott-Raven Publishers, Philadelphia 1996, pp. 577-586.

    Google Scholar 

  57. Massy Z.A., Mamzer-Bruneel M.F., Chevalier A., Millet P., Helenon O., Chadefaux-Vekemans B., Legendre C., Bader C., Drueke T., Lacour B., Kreis H. Carotid atherosclerosis in renal transplant recipients. Nephrol. Dial. Transplant. 1998, 13: 1792–1798.

    Article  CAS  PubMed  Google Scholar 

  58. Wahlers T., Fieguth H.G., Jurmann M., Albes J., Hausen B., Demertzis S., Schafers H.J., Oppelt P., Mugge A, Borst H.G. Graft coronary vasculopathy in cardiac transplantation-evaluation of risk factors by multivariate analysis. Eur. J. Cardiothorac. Surg. 1996, 10: 1–5.

    Article  CAS  PubMed  Google Scholar 

  59. McGiffin D.C., Savunen T., Kirklin J.K., Naftel D.C., Bourge R.C., Paine T.D., White-Williams C., Sisto T., Early L. Cardiac transplant coronary artery disease. A multivariable analysis of pretranssplantation risk factors for disease development and morbid events. J. Thorac. Cardiovasc. Surg. 1995, 109: 1088–1089.

    Google Scholar 

  60. Brunner-La Rocca H.P., Schneider J., Kunzli A., Turina M., Kiowski W. Cardiac allograft rejection late after transplantation is a risk factor for graft coronary artery disease. Transplantation 1998, 65: 538–543.

    Article  CAS  PubMed  Google Scholar 

  61. Sharples L.D., Caine N., Mullins P., Scott J.P., Solis E., English T.A., Large S.R., Schofield P.M., Wallwork J. Risk factor analysis for the major hazards following heart transplantation-rejection, infection, and coronary occlusive disease. Transplantation 1991, 52: 244–252.

    Article  CAS  PubMed  Google Scholar 

  62. Gao S.Z., Hunt S.A., Schroeder J.S., Alderman E.L., Hill I.R., Stinson E.B. Early development of accelerated graft coronary artery disease: risk factors and course. J. Am. Coll. Cardiol. 1996, 28: 673–679.

    Article  CAS  PubMed  Google Scholar 

  63. Mehra M.R., Ventura H.O., Chambers R.B., Ramireddy K., Smart F.W., Stapleton D.D. The prognostic impact of immunosuppression and cellular rejection on cardiac allograft vasculopathy: time for a reappraisal. J. Heart Lung Transplant. 1997, 16: 743–751.

    CAS  PubMed  Google Scholar 

  64. Eich D., Thompson J.A., Ko D.J., Hastillo A., Lower R., Kats S., Kats M., Hess M.L. Hypercholesterolemia in long-term survivors of heart transplantation: an early marker of accelerated coronary artery disease. J. Heart Lung Transplant. 1991, 10: 45–49.

    CAS  PubMed  Google Scholar 

  65. Escobar A., Ventura H.O., Stapleton D.D., Mehra M.R., Ramee S.R., Collins T.J., Jain S.P., Smart F.W., White C.J. Cardiac allograft vasculopathy assessed by intravascular ultrasonography and nonimmunologic risk factors. Am. J. Cardiol. 1994, 74: 1042–1046.

    Article  CAS  PubMed  Google Scholar 

  66. Drew A.F., Tipping P.G. Cyclosporine treatment reduces early atherosclerosis in the cholesterol-fed rabbit. Atherosclerosis 1995, 116: 181–189.

    Article  CAS  PubMed  Google Scholar 

  67. Andersen H.O., Madsen G., Nordestgaard B.G., Hansen B.F., Kjeldson K., Stender S. Cyclosporin suppresses transplant arteriosclerosis in the aorta-allografted, cholesterol-clamped rabbit. Suppression preceded by decrease in arterial lipoprotein permeability. Arterioscler. Thromb. 1994, 14: 944–950.

    Article  CAS  PubMed  Google Scholar 

  68. Andersen H.O., Holm P., Stender S., Hansen B.F., Nordestgaard B.G. Dose-dependent suppression of transplant arteriosclerosis in aorta-allografted, cholesterol-clamped rabbits. Suppression not eliminated by the cholesterol-raising effect of cyclosporine. Arterioscler. Thromb. Vasc. Biol. 1997, 17: 2515–2515.

    Article  CAS  PubMed  Google Scholar 

  69. Koch M., Gradaus F., Schoebel F.C., Leschke M., Grabensee B. Relevance of conventional cardiovascular risk factors for the prediction of coronary artery disease in diabetic patients on renal replacement the-rapy. Nephrol. Dial. Transplant. 1997, 12: 1187–1191.

    Article  CAS  PubMed  Google Scholar 

  70. Suwelack B., Witta J., Hausberg M., Muller S., Rahan K.H., Barenbrock M. Studies on structural changes of the carotid arteries and the heart in asymptomatic renal transplant recipients. Nephrol. Dial. Transplant. 1999, 14: 160–165.

    Article  CAS  PubMed  Google Scholar 

  71. Barbagallo C.M., Pinto A., Gallo S., Parrinello G., Caputo F., Sparacino V., Cefalu A.B., Novo S., Licata G., Notarbartolo A., Averna M.R. Carotid atherosclerosis in renal transplant recipients: relationships with cardiovascular risk factors and plasma lipoproteins. Transplantation 1999, 67: 366–371.

    Article  CAS  PubMed  Google Scholar 

  72. Anker S., Ivens K., Grabensee B., Heering P. Cardiovascular risk factors and diseases after renal transplantation. Int. Urol. Nephrol. 1998, 30: 777–788.

    Article  Google Scholar 

  73. Dimeny E., Wahlberg J., Lithell H., Fellstrom B. Hyperlipidaemia in renal transplantation. Risk factors for long-term graft outcome. Eur. J. Clin. Invest. 1995, 25: 574–583.

    Article  CAS  PubMed  Google Scholar 

  74. Schrama Y.C., Hene R.J., De Jonge N., Joles J.A., Van Rijn H.J., Bar D.R., Ververs T.F., Van Tol A., Koomans H.A. Transplantation 1998, 66: 1175–1181.

    Article  CAS  PubMed  Google Scholar 

  75. Li P.K., Mak T.W., Chan T.H., Wang A., Lam C.W., Lai K.N. Effect of fluvastatin on lipoprotein profiles in treating renal transplant recipients with dyslipoproteinemia. Transplantation 1995, 60: 652–656.

    Article  CAS  PubMed  Google Scholar 

  76. Holdaas H., Hartmann A., Stenstrom J., Dahl K.J., Borge M., Pfister P. Effect of fluvastatin for safely lowering atherogenic lipids in renal transplant patients receiving cyclosporine. Am. J. Cardiol. 1995, 76: 102–104.

    Article  Google Scholar 

  77. Wenke K., Meiser B., Thiery J., Nagel D., Scheidt W., Steinbeck G., Seidel D., Reichart B. Simvastatin reduces graft vessel disease and mortality after heart transplantation. A four-year randomized trial. Circulation 1997, 96: 1398–1402.

    Article  CAS  PubMed  Google Scholar 

  78. Campana C., Iacona I., Regazzi M.B., Gavazzi A., Perani G., Raddato V., Montemartini C., Vigano M. Efficacy and pharmacokinetics of simvastatin in heart transplant recipients. Ann. Pharmacother. 1995, 29: 235–239.

    CAS  PubMed  Google Scholar 

  79. Blaison G., Weber J.C., Sachs D., Korganow A.S., Martin T., Kretz J.G., Pasquali J.L. Rhabdomyolysis caused by simvastatinin a patient following heart transplantation and cyclosporine therapy. Rev. Med. Int. 1992, 13: 61–63.

    Article  CAS  Google Scholar 

  80. Kreuzer J., Bader J., Jahn L., Hauptmann M., Kubler W., Von Hodenberg E. Chemotaxis of the monocyte line U937: dependence on cholesterol and early mevalonate pathway products. Atherosclerosis 1991, 90: 203–209.

    Article  CAS  PubMed  Google Scholar 

  81. Kirby J., Givan A.L., Shenton B.K., Talbot D., Forsythe J.L.R., Lennard T.W.J., Proud G., Taylor R.M.R. Renal allograft rejection: possible involvement of antibody-dependent cell-mediated cytotoxicity. Transplantation 1990, 50: 225–229.

    Article  CAS  PubMed  Google Scholar 

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  1. Dipartimento di Endocrinologia e Metabolismo, Sezione Metabolismo, Ospedale Cisanello, University of Pisa, Via Paradisa, 2, 56100, Pisa, Italy

    Piero Marchetti M.D. & R. Navalesi

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Marchetti, P., Navalesi, R. The metabolic effects of cyclosporin and tacrolimus. J Endocrinol Invest 23, 482–490 (2000). https://doi.org/10.1007/BF03343761

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