Skip to main content
Log in

The pathophysiology of sandimmune (cyclosporine) in man and animals

  • Occasional Survey
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Part II: The side-effects of Sandimmune that have also been observed clinically include hepatic dysfunction, glucose intolerance, thrombo-embolic complications and nervous system disorders. To determine the cause and significance of such effects, the actions of Sandimmune on the liver, the pancreas, on hematostasis and the nervous system were examined. Comparisons were made between animal and human data obtained in vivo and in vitro, and the clinical setting under which the side-effects occur was analyzed. The actions of Sandimmune on the liver seem to reflect mostly a cholestasis with a small depression in protein synthesis and a mild disturbance in lipid metabolism of uncertain origin. The action of Sandimmune on the pancreas suggests insulin resistance and possibly a secretory disturbance, with no evidence for depressed insulin synthesis, except in animals at high doses. Sandimmune does not seem to promote thromboembolism in man, although fibrinolysis may be depressed and platelet aggregation can be enhanced. The effects of Sandimmune on the nervous system are unclear, for tremor is common but of uncertain origin, whereas seizures and encephalopathy are rare and invariably associated with other risk factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Whiting PH, Cunningham C, Thomson AW, Simpson JG (1984) Enhancement of high dose cyclosporin A toxicity by frusemide. Biochem Pharmacol 33: 1075–1079

    Google Scholar 

  2. Farthing MJG, Clark ML, Pendry A, Sloane J, Alexander P (1981) Nature of the toxicity of cyclosporin A in the rat. Biochem Pharmacol 30: 3311–3316

    Google Scholar 

  3. Hahn HJ, Laube F, Lucke S, Klöting I, Kohnert KD, Warzock R (1986) Toxic effects of cyclosporine on the endocrine pancreas of Wistar rats. Transplantation 41: 44–47

    Google Scholar 

  4. Blair JT, Thomson AW, Whiting PH, Davidson RJL, Simpson JG (1982) Toxicity of the immune suppressant cyclosporin A in the rat. J Pathol 138: 163–178

    Google Scholar 

  5. Yagisawa T, Takahashi K, Teraoka S, Yamaguchi Y, Toma H, Agishi T, Ota K (1986) Cyclosporine tissue levels and morphological and functional changes in organs of cyclosporine-treated rats. Transplant Proc 18: 1272–1277

    Google Scholar 

  6. Le Thai B, Dumont M, Michel A, Erlinger S, Houssin D (1988) Cholestatic effect of cyclosporine in the rat. An inhibition of bile acid secretion. Transplantation 46: 510–512

    Google Scholar 

  7. Stone B, Warty V, Dindzans V, Van Thiel D (1988) The mechanism of cyclosporine-induced cholestasis in the rat. Transplant Proc 20 [Suppl 3]: 841–844

    Google Scholar 

  8. Teraoka S, Sanaka T, Takahashi K, Toma H, Yamaguchi Y, Yagisawa T, Tanabe K, Sato H, Matsumura O, Nakajima I, Kawai T, Honda H, Fuchinoue S, Agishi T, Ota K (1988) Stimulation of intrinsic prostacyclin synthesis and inhibition of thromboxane production to minimize cyclosporine nephrotoxicity. Transplant Proc 20 [Suppl 3]: 638–645

    Google Scholar 

  9. Whiting PH, Barnard N, Neilsch A, Simpson JG, Burke MD (1987) Interactions between cyclosporin A, indomethacin and 16,16-dimethyl prostaglandin E2: effects on renal, hepatic and gastrointestinal toxicity in the rat. Br J Exp Pathol 68: 777–786

    Google Scholar 

  10. Hahn HJ, Dunger A, Laube F, Besch W, Radloff E, Kauert C, Kotzke G (1986) Reversibility of the acute toxicity effect of cyclosporin A on pancreatic B cells of Wistar rats. Diabetologia 29: 489–494

    Google Scholar 

  11. Kaskel FJ, Devarajan P, Arbeit LA, Partin JS, Moore LC (1987) Cyclosporinc nephrotoxicity: sodium excretion, autoregulation, and angiotensin II. Am J Physiol 252: F733-F742

    Google Scholar 

  12. Evans GO (1988) Hypomagnesaemia, hypoalbuminaemia and plasma lipid changes in rats following the oral administration of ciclosporin. Comp Biochem Physiol 89 [C]: 375–376

    Google Scholar 

  13. Jevnikar AM, Petric P, Holub BJ, Phibrick DJ, Clark WF (1988) Effect of cyclosporine on plasma lipids and modification with dietary fish oil. Transplantation 46: 722–725

    Google Scholar 

  14. Levy E, Roy CC, Bonin A, Gurbindo C, Thibault L, Letarte J, Sabbah S, Atlan P, Seidman E (1988) Cyclosporine A induced lipid abnormalities in clinical and experimental conditions. Gastroenterology 94: A260

    Google Scholar 

  15. Riegel W, Brehmer D, Thaiss F, Keller E, Hörl WH (1989) Effect of cyclosporin A on carbohydrate metabolism in the rat. Transplant Int 2: 8–12

    Google Scholar 

  16. Rotolo FS, Braunum GD, Bowers BA, Myers WC (1986) Effect of cyclosporine on bile secretion in rats. Am J Surg 151: 35–40

    Google Scholar 

  17. Stacey NH, Kotecka B (1988) Inhibition of taurocholate and ouabain transport in isolated rat hepatocytes by cyclosporin A. Gastroenterology 95: 780–786

    Google Scholar 

  18. Kukongviriyapan V, Stacey NH (1988) Inhibition of taurocholate transport by cyclosporin A in cultured rat hepatocytes. J Pharmacol Exp Ther 247: 685–689

    Google Scholar 

  19. Boelsterli UA, Bouis P, Brouillard JF, Donatsch P (1988) In vitro toxicity assessment of cyclosporin A and its analogs in a primary rat hepatocyte culture model. Toxicol Appl Pharmacol 96: 212–221

    Google Scholar 

  20. Ziegler K, Frimmer M, Koepsell H (1988) Photoaffinity labelling of membrane proteins from rat liver and pig kidney with cyclosporine diazirine: Involvement of binding to plasma membranes cytotoxic effects. Transplantation 46 [Suppl]: 15S-20S

    Google Scholar 

  21. Moseley RH, Johnson TR, Morrissette JM (1989) Cyclosporine (CsA) inhibition of taurocholate transport in rat liver plasma membrane vesicles. Gastroenterology 96: A634

    Google Scholar 

  22. Vine W, Billiar T, Simmons R, Bowers LD (1988) Cyclosporine-induced hepatotoxicity: a microassay by hepatocytes in tissue culture. Transplant Proc 20 [Suppl 3]: 859–862

    Google Scholar 

  23. Buss WC, Stepanek J, Bennet WM (1989) A new proposal for the mechanism of cyclosporine A nephrotoxicity. Biochem Pharmacol 38: 4085–4093

    Google Scholar 

  24. Bäckman L, Appelkvist EL, Ringden O, Dallner G (1988) Effects of cyclosporine A on hepatic protein synthesis. Transplant Proc 20 [Suppl 3]: 853–858

    Google Scholar 

  25. Betschart JM, Virji MA, Shinozuka H (1988) Cyclosporine A-induced alteractions in rat hepatic glycogen metabolism. Transplant Proc 20 [Suppl 3]: 880–884

    Google Scholar 

  26. Son H, Cha B, Lee K, Kang S (1988) Effects of cyclosporin A on pancreatic islets and insulin action in isolated fat cells of the rat. Diabetes Res Clin Pract 5 [Suppl 1]: S236

    Google Scholar 

  27. Hochman L, Ströchlein K, Van Buren C, Bossart M, Zirl R, McAllister H, Radovancevic B, Frazier OH (1986) Histopathologic and ultrastructural changes of the liver in heart transplant patients with cyclosporine-induced hepatotoxicity. J Heart Transplant 5: 377

    Google Scholar 

  28. Schade RR, Guglielmi A, Thiel DH van, Thompson ME, Warty V, Griffith B, Sanghvi A, Bahnson H, Hardesty R (1983) Cholestasis in heart transplant recipients treated with cyclosporine. Transplant Proc 15 [Suppl 1/2]: 2757–2760

    Google Scholar 

  29. Gulbis B, Adler M, Ooms HA, Desmet JM, Leclerc JL, Primo G (1988) Liver-function studies in heart-transplant recipients treated with cyclosporin A. Clin Chem 34: 1772–1774

    Google Scholar 

  30. European Multicentre Trial Group (1983) Cyclosporin in cadaveric renal transplantation: one-year follow-up of a multicenter trial. Lancet II: 986–989

    Google Scholar 

  31. Hillebrand G, Castro LA, Habersetzer R, Stoffner D, Schneider B, Gokel JM, Gurland HJ, Land W (1986) Chronic cyclosporine hepatotoxicity after renal transplantation. Transplant Proc 18: 1020–1022

    Google Scholar 

  32. Rodger RSC, Turney JH, Haines I, Michael J, Adu D, McMaster P (1983) Cyclosporine and liver function in renal allograft recipients. Transplant Proc 15 [Suppl 1/2]: 2754–2756

    Google Scholar 

  33. Ellis CN, Gorsulowsky DC, Hamilton TA, Billings JK, Brown MD, Headington JT, Cooper KD, Baadsgaard O, Duell EA, Annesley TM, Turcotte JG, Voorhees JJ (1986) Cyclosporine improves psoriasis in a double-blind study. JAMA 256: 3110–3116

    Google Scholar 

  34. Ballantyne CM, Podel EJ, Patsch WP, Harati Y, Appel V, Gotto AM, Young JB (1989) Effects of cyclosporine therapy on plasma lipoprotein levels. JAMA 262:53–56

    Google Scholar 

  35. Laupacis A, Keown PA, Ulan RA, Sinclair NR, Stiller CR (1981) Hyperbilirubinaemia and cyclosporin A levels. Lancet II: 1426–1427

    Google Scholar 

  36. Loertscher R, Wenk M, Harder F, Brunner F, Follath F, Thiel G (1981) Hpyerbilirubinaemia and cyclosporin A levels in renal transplant patients. Lancet II: 635–636

    Google Scholar 

  37. Loertscher R, Thiel G, Harder F, Brunner FP (1983) Persistent elevation of alkaline phosphatase in cyclosporine-treated renal transplant recipients. Transplantation 36: 115–116

    Google Scholar 

  38. Kahan BD, Flechner SM, Lorber MI, Golden D, Conley S, Van Buren CT (1987) Complications of cyclosporine-prednisone immunosuppression in 402 renal allograft recipients exclusively followed at a single center for from one to five years. Transplantation 43: 197–204

    Google Scholar 

  39. Price CP, Deam SM, Calvin J (1983) Serum alkaline phosphatase isoenzyme in patients on cyclosporin A following renal transplantation. Clin Biochem 16: A25

    Google Scholar 

  40. Barton CH, Varizi ND, Martin DC, Choi S, Alikhani S (1987) Hypomagnesemia and renal magnesium wasting in renal transplant recipients receiving cyclosporine. Am J Med 83: 693–699

    Google Scholar 

  41. Lohri A, Huser B, Lämmle B, Oberholzer M, Thiel G, Duckert F (1987) Factor XII, plasma prekallikrein, α2 and c1-inhibitor levels in renal allograft recipients during immunosuppression with cyclosporin A. Sequential measurements over four months in 17 patients. Thromb Haemost 58: 993–997

    Google Scholar 

  42. Watzke H, Spielberger M, Leithner C, Steiner E, Schwarz HP, Aigner F, Scheiber V, Margreiter R (1986) Hemostasis after renal transplantation: comparison of three different immunosuppressive regimens. Transplant Proc 18: 1025–1028

    Google Scholar 

  43. Leunissen KML, Teule J, Degenaar CP, Kho TL, Frenken LAM, Hooff JP van (1987) Impairment of liver synthetic function and decreased liver flow during cyclosporin A therapy. Transplant Proc 19: 1822–1824

    Google Scholar 

  44. Harris KPG, Russel GI, Parvin SD, Veitch PS, Walls J (1986) Alterations in lipid and carbohydrate metabolism attributable to cyclosporin A in renal transplant recipients. Br Med J 292: 16

    Google Scholar 

  45. Versluis DJ, Wenting GJ, Derkx FHM, Schalekamp MADH, Jeckel J, Weimar W (1987) Who should be converted from cyclosporine to conventional immunosuppression in kidney transplantation, and why? Transplantation 44: 387–389

    Google Scholar 

  46. Raine AEG, Carter R, Mann JI, Morris PJ (1988) Adverse effect of cyclosporin on plasma cholesterol in renal transplant recipients. Nephrol Dial Transplant 3: 458–463

    Google Scholar 

  47. Markell MS, Brown CD, Butt KMH, Friedman EA (1989) Prospective evaluation of changes in lipid profiles in cyclosporine-treated renal transplant patients. Transplant Proc 21: 1497–1499

    Google Scholar 

  48. Schorn T, Kliem V, Bojanovski D, Repp H, Frei U, Vogt P, Pichlmayr R, Koch KM (1988) Long-term immunosuppressive therapy and lipid abnormalities in renal transplant recipients. Nephrol Dial Transplant 3: 581

    Google Scholar 

  49. Stamler JS, Vaughan DE, Rudd MA, Mudge GH, Kirshenbaum J, Young P, Alexander RW, Loscalzo J (1988) Frequency of hypercholesterolemia after cardiac transplantation. Am J Cardiol 62: 1268–1272

    Google Scholar 

  50. Ballantyne CM, Jones PH, Payton-Ross C, Patsch W, Short HD, Noon GP, Gotto AM, DeBakey ME, Young JB (1987) Hyperlipidemia following heart transplantation: natural history and intervention with mevinolin (lovastatin). Transplant Proc 19 [Suppl 5]: 60–62

    Google Scholar 

  51. Eich D, Hastillo A, Thompson JA, Lower RR, Hess ML (1986) Hypercholesterolemia in long-term survivors of heart transplantation. J Heart Transplant 5: 377

    Google Scholar 

  52. Keogh A, Simons L, Spratt P, Esmore D, Chang V, Hickie J, Baron D (1988) Hyperlipidemia after heart transplantation. J Heart Transplant 7: 171–175

    Google Scholar 

  53. Becker DM, Chamberlain B, Swank R, Hegewald MG, Girardet R, Baughman KL, Kwiterovich PO, Pearson TA, Ettinger WH, Renlund D (1988) Relationship between corticosteroid exposure and plasma lipid levels in heart transplant recipients. Am J Med 85: 632–638

    Google Scholar 

  54. Derfler K, Hayde M, Balcke P, Widhalm K (1988) Pathological decrease in lipoprotein lipase activity in renal transplant recipients immunosuppressed with cyclosporin. Nephrol Dial Transplant 3: 569–570

    Google Scholar 

  55. Lorber MI, Van Baren CT, Flechner SM, Williams C, Kahan BD (1987) Hepatobiliary and pancreatic complications of cyclosporine therapy in 466 renal transplant recipients. Transplantation 43: 35–40

    Google Scholar 

  56. Klintmalm GBG, Iwatsuki S, Starzl TE (1981) Cyclosporin A hepatotoxicity in 66 renal allograft recipients. Transplantation 32: 488–489

    Google Scholar 

  57. Atkinson K, Biggs J, Dodds A, Concannon A (1983) Cyclosporine-associated hepatotoxicity after allogeneic marrow transplantation in man: differentiation from other causes of posttransplant liver disease. Transplant Proc 15 [Suppl 1/2]: 2761–2767

    Google Scholar 

  58. Canafax DM, Simmons RL, Sutherland DER, Fryd DS, Strand MH, Ascher NL, Payne WD, Najarian JS (1988) Early and late effects of two immunosuppressive drug protocols on recipients of renal allografts: results of the Minnesota randomized trial comparing cyclosporine versus antilymphocyte globulin-azathioprine. Transplant Proc 18 [Suppl 1]: 192–196

    Google Scholar 

  59. Hess ML, Hastillo A, Thompson JA, Sansonetti DJ, Szentpetery S, Barnhart G, Lower RR (1987) Lipid mediators in organ transplantation: does cyclosporine accelerate coronary atherosclerosis? Transplant Proc 19 [Suppl 5]: 71–73

    Google Scholar 

  60. Gao SZ, Schroeder J, Alderman E, Hunt S, Valantine H, Wiederhold V (1988) Incidence of accelerated coronary artery disease in heart transplant survivors: comparison of cyclosporin and azathioprine regimen. Circulation 78 [Suppl II]: II-280

    Google Scholar 

  61. Vathsala A, Weinberg RB, Schoenberg L, Grevel J, Goldstein RA, Van Buren CT, Lewis RM, Kahan BD (1989) Lipid abnormalities in cyclosporine-prednisone-treated renal transplant recipients. Transplantation 48: 37–43

    Google Scholar 

  62. Renlund DG, Bristow MR, Crandall BG, Burton NA, Doty DB, Karwande SV, Gay WA, Jones KW, Hegewald MG, Hagan ME, Lee HR, O'Connell JB (1989) Hypercholesterolemia after heart transplantation: amelioration by corticosteroid-free maintenance immunosuppression. J Heart Transplant 8: 214–220

    Google Scholar 

  63. Livi U, Bortolotti U, Faggian G, Mazzucco A, Stellin G, Michielon G, Gallucci V (1989) Effects of immunosuppression on glucose and lipid metabolism after heart transplantation. Transplant Proc 21: 2477–2478

    Google Scholar 

  64. Taylor DO, Thompson JA, Hastillo A, Barnhart G, Rider S, Lower RR, Hess ML (1989) Hyperlipidemia after clinical heart transplantation. J Heart Transplant 8: 209–213

    Google Scholar 

  65. Müller MK, Bergmann K, Degenhardt H, Klöppel G, Löhr M, Coone HJ, Goebell H (1988) Differential sensitivity of rat exocrine and endocrine pancreas to cyclosporine. Transplantation 45: 698–700

    Google Scholar 

  66. Yale JF, Roy RD, Grose M, Seemayer TA, Murphy GF, Marliss EB (1985) Effects of cyclosporine on glucose tolerance in the rat. Diabetes 34: 1309–1313

    Google Scholar 

  67. Helmchen U, Schmidt WE, Siegel EG, Creutzfeldt W (1984) Morphological and functional changes of pancreatic B-cells in cyclosporin A-treated rats. Diabetologia 27: 416–418

    Google Scholar 

  68. Mirkovitch V, Augstburger M, Temler E, Winistörfer B, Biollaz J, Appenzeller MB, Felberg JP (1986) Influence of cyclosporine on the function and morphology of the rat pancreas. Transplant Proc 18: 1171–1174

    Google Scholar 

  69. Thomson KJ, Saunders NJ, Simpson JG, Whiting PH (1987) The effect of cyclosporin on glucose homeostasis. Nephrol Dial Transplant 2: 62

    Google Scholar 

  70. Hamaguchi K, Nakamura M, Ono J, Takaki R (1988) Ultrastructural and functional studies of pancreatic B cells in Wistar rats treated with immunotherapeatic doses of cyclosporin. Diabetes Res Clin Pract 5: 135–143

    Google Scholar 

  71. Eun HM, Pak CY, Kim CJ, McArthur RG, Yoon JW (1987) Role of cyclosporin A in macromolecular synthesis of β-cells. Diabetes 36: 952–958

    Google Scholar 

  72. Jablenska R (1989) The effect of cyclosporin A on the endocrine pancreas of rats. Exp Clin Endocrinol 93: 208–212

    Google Scholar 

  73. Teraoka S, Kawai T, Yamaguchi Y, Tojinbara T, Fujita S, Nakajima I, Nakagawa Y, Fujikawa H, Hayashi T, Honda H, Fuchinoue S, Agishi T, Ota K (1989) Cyclosporine-associated toxicity in pancreatic islet cells and its prevention by K-MAP in cyclosporinetreated animals. Transplant Proc 21: 2774–2779

    Google Scholar 

  74. Löhr M, Müller MK, Goebell H, Klöppel G (1989) Prostaglandin analogue protects pancreatic B-cells against cyclosporin A toxicity. Experientia, Basel 45: 352–355

    Google Scholar 

  75. Hesse UJ, Stock P, Sutherland DER, Dunning M, Najarian JS (1986) Cyclosporine and glucose metabolism. Transplant Proc 18: 1554–1555

    Google Scholar 

  76. Stegall MD, Chabot JA, Engelstad K, Jin MX, Weber C, Reemtsma K, Hardy MA (1989) The effect of cyclosporine on the glucose tolerance of normal monkeys. Transplant Proc 21: 926–927

    Google Scholar 

  77. Riegel W, Brehmer D, Thaiss F, Keller E, Hörl WH (1989) Effect of cyclosporin A on carbohydrate metabolism in the rat. Transplant Int 2: 8–12

    Google Scholar 

  78. Yale JF, Chamelian M, Courchesne S, Vigeant C (1988) Peripheral insulin resistance and decreased insulin secretion after cyclosporine A treatment. Transplant Proc 20 [Suppl 3]: 985–988

    Google Scholar 

  79. Fehmann HC, Haverich R, Stöckmann F, Creuzfeldt W (1987) Cyclosporine A in low doses induces functional and morphologic changes in rat pancreatic B cells. Transplant Proc 19: 4015–4016

    Google Scholar 

  80. McAuley FT, Simpson JG, Thomson AW, Whiting PH (1987) Cyclosporin A induced nephrotoxicity in the rat: relationship to increased plasma renin activity. Agents Actions 21: 209–216

    Google Scholar 

  81. Stöckmann F, Fehmann HC, Göke B, Siegel EG, Creutzfeldt W (1989) Impairment of stimulated insulin release from the isolated perfused rat pancreas by cyclosporine pretreatment. Transplantation 48: 381–385

    Google Scholar 

  82. Chandrasekar B, Mukherjee SK (1988) Effect of prolonged administration of cyclosporin A on (pro)insulin biosynthesis and insulin release by rat islets of Langerhans. Biochem Pharmacol 37: 3609–3611

    Google Scholar 

  83. Rebuffat P, Kasprzak A, Andreis PG, Mazzocchi G, Gottardo G, Coi A, Nussdorfer GG (1989) Effects of prolonged cyclosporine-A treatment on the morphology and function of rat adrenal cortex. Endocrinology 125: 1407–1413

    Google Scholar 

  84. Garvin PJ, Niehoff M, Staggenborg J (1988) Cyclosporine's effect on canine pancreatic endocrine function. Transplantation 45: 1027–1031

    Google Scholar 

  85. Faraci M, Vigeant C, Yale JF (1988) Toxic effects of cyclosporine A and G in Wistar rats. Transplant Proc 20 [Suppl 3]: 963–968

    Google Scholar 

  86. Gillison SL, Bartlett ST, Curry DL (1989) Synthesis-secretion coupling of insulin: Effect of cyclosporin. Diabetes 38: 465–470

    Google Scholar 

  87. Whiting PH, Simpson JG (1988) Lithium clearance measurements as an indication of cyclosporin A nephrotoxicity in the rat. Clin Sci 74: 173–178

    Google Scholar 

  88. Bertani T, Perico N, Abbate M, Battaglia C, Remuzzi G (1987) Renal injury induced by long-term administration of cyclosporin A to rats. Am J Pathol 127: 569–579

    Google Scholar 

  89. Chan P, Scoble JE, Senior JM, Varghese Z, Sweny P, Moorhead JF (1989) Cyclosporin inhibition of glucose transport in cell culture. Transplant Proc 21: 922–923

    Google Scholar 

  90. Inselmann G, Blank M, Baumann K (1988) Cyclosporine A induced lipid peroxidation in microsomes and effect on active and passive glucose transport by brush border membrane vesicles of rat kidney. Res Commun Chem Pathol Pharmacol 62: 207–220

    Google Scholar 

  91. Falholt K, Jensen SL, Heding LG, Falholt W (1987) Influence of cyclosporin A and prednisolone on intermediary glucose and lipid metabolism. Diabetes 36 [Suppl 1]: 188A

    Google Scholar 

  92. Suzuki S, Oka T (1989) Inhibitory effects of cyclosporin on exocrine and endocrine functions of the rat pancreas. Transplant Proc 21: 913–914

    Google Scholar 

  93. Elalamy I, Myara I, Cosson C, Fabre M, Moatti N (1988) Amylase, isoamylase and lipase activities in cyclosporine-treated rats. Clin Chem 34: 2583

    Google Scholar 

  94. Basadonna G, Montorsi F, Kakizaki K, Merrell RC (1988) Cyclosporin A and islet function. Am J Surg 156: 191–193

    Google Scholar 

  95. Alejandro R, Feldman EC, Bloom AD, Kenyon NS (1989) Effects of cyclosporin in insulin and C-peptide secretion in healthy beagles. Diabetes 38: 698–703

    Google Scholar 

  96. Andersson A, Borg H, Hallberg A, Hellerström C, Sandler S, Schnell A (1984) Long-term effects of cyclosporin A on cultured mouse pancreatic islets. Diabetologia 27: 66–69

    Google Scholar 

  97. Laube F, Hahn GJ (1985) Effect of cyclosporin-A on insulin secretion in vitro. Horm Metab Res 17: 43–44

    Google Scholar 

  98. Ferrero ME, Marni A, Gaja G (1989) Stimulation of insulin release from rat pancreatic islets induced by cyclosporine. Biochem Soc Trans 17: 351–352

    Google Scholar 

  99. Yates AP, Gordon C, Wise MH, Davies D (1986) The effect of cyclosporine A on glucose-induced insulin secretion from isolated perfused islets of the mouse. Transplant Proc 18: 1160–1161

    Google Scholar 

  100. Robertson RP (1986) Cyclosporin-induced inhibition of insulin secretion in isolated rat islets and HIT cells. Diabetes 35: 1016–1019

    Google Scholar 

  101. Draznin B, Metz SA, Sussman KE, Leitner JW (1988) Cyclosporin-induced inhibition of insulin release. Possible role of voltage-dependent calcium transport channels. Biochem Pharmacol 37: 3941–3945

    Google Scholar 

  102. Bedoya FJ, Martin F (1989) In vitro effects of cyclosporin A on secretagogue-induced insulin release by isolated islets. Diabetologia 32: 465A

    Google Scholar 

  103. Höcker M, Wilms H, Schmidt WE, Vorhauer B, Fölsch UR (1989) Influence of cyclosporin A on basal and stimulated amylase secretion of isolated pancreatic acini of the rat. Digestion 43: 150

    Google Scholar 

  104. Gunnarsson R, Klintmalm G, Lundgren G, Tydén G, Wilczek H, Oestman J, Groth CG (1984) Deterioration in glucose metabolism in pancreatic transport recipients after conversion from azathioprine to cyclosporine. Transplant Proc 16: 709–712

    Google Scholar 

  105. Smith WGJ, Thomas S, Griffin PJA, Salaman JR (1989) Comparative effects of immunosuppressive therapy on glucose metabolism. Transplant Proc 21: 1502–1503

    Google Scholar 

  106. Carroccio A, Galione A, Vaccaro F, Montalto G, Notabartolo A (1989) Cyclosporine A treatment: influence on pancreatic islet cells. In: Touraine JL, Traeger J, Betnel H, Dubernard JM, Revillard JP, Dandon P (eds) Transplantation and clinical immunology, vol 20. Combined immunosuppressive therapy in transplantation. Excerpta Medica, Amsterdam, pp 176–178

    Google Scholar 

  107. Robertson RP, Franklin G, Nelson L (1989) Glucose homeostasis and insulin secretion during chronic treatment with cyclosporin in nondiabetic humans. Diabetes 38 [Suppl 1]: 99–100

    Google Scholar 

  108. Robertson RP, Franklin G, Nelson L (1989) Intravenous glucose tolerance and pancreatic islet β-cell function in patients with multiple sclerosis during 2 year treatment with cyclosporin. Diabetes 38: 58–64

    Google Scholar 

  109. Raptis S, Mitrakou A, Halvatsiotis P, Hatziagelaki E (1989) Normal glucose tolerance test after 3 years of cyclosporine treatment in nondiabetic patients. Diabetes 38 [Suppl 2]: 155A

    Google Scholar 

  110. Engfeldt P, Tydén G, Gunnarsson R, Oestman J, Groth CG (1986) Impaired glucose tolerance with cyclosporine. Transplant Proc 18: 65–66

    Google Scholar 

  111. Oest L, Tydén G, Fehrman I (1988) Impaired glucose tolerance in cyclosporine-prednisolone-treated renal graft recipients. Transplantation 46: 370–372

    Google Scholar 

  112. Griffin PJA, Owens DR, Luzio S, Salaman JR (1989) Serial glucose tolerance assessment during cyclosporine therapy. Transplant Proc 21: 1495–1496

    Google Scholar 

  113. Nakai I, Omori Y, Aikawa I, Yasumura T, Suzuki S, Yoshimura N, Arakawa K, Matsui S, Oka T (1988) Effect of cyclosporine on glucose metabolism in kidney trnasplant recipients. Transplant Proc 20 [Suppl 3]: 969–978

    Google Scholar 

  114. Smith JL, Hunsicker LG, Yuh WTC, Wright FH, Voorhis L van, Corry RJ (1989) Appearance of type II diabetes mellitus in type I diabetic recipients of pancreas allografts. Transplantation 47: 304–311

    Google Scholar 

  115. Yoshimura N, Nakai I, Ohmori Y, Aikawa I, Fukuda M, Yasumura T, Matsui S, Hamashima T, Oka T (1988) Effect of cyclosporine on the endocrine and exocrine pancreas in kidney transplant recipients. Am J Kidney Dis 12: 11–17

    Google Scholar 

  116. Ihara H, Ogino T, Hosokawa S, Yabumoto H, Arima M, Ikoma F (1989) Perioperative hyperamylasemia in cyclosporine-treated renal transplant recipients: does it have clinical significance. Transplant Proc 21: 2147–2150

    Google Scholar 

  117. Prevost X, Myara I, Cosson C, DuBoust A, Moatti N (1988) Asymptomatic hyperamylasemia after cyclosporine therapy in patients with renal transplants. Transplant Proc 20: 555–558

    Google Scholar 

  118. Frick TW, Fryd DS, Sutherland DER, Goodale RL, Simmons RL, Najarian JS (1987) Hypercalcemia associated with pancreatitis and hyperamylasemia in renal transplant recipients. Data from the Minnesota randomized trial of cyclosporine versus antilymphoblast azathioprine. Am J Surg 154: 487–489

    Google Scholar 

  119. Tuch BE, Viketos S, Grigoriou S, Turtle JR (1987) Lack of toxicity of cyclosporine A on the human fetal pancreas. Transplant Proc 19: 1257–1258

    Google Scholar 

  120. Jutte NHPM, Heyse P, Bruining GJ, Zeilmaker GH, Weimar W (1987) Effect of cyclosporine A on glucose-induced insulin secretion by isolated human islets of Langerhans. Transplant Proc 19: 4152–4153

    Google Scholar 

  121. Nielsen JH, Mandrup-Poulsen T, Nerup J (1986) Direct effects of cyclosporin A on human pancreatic β-cells. Diabetes 35: 1049–1052

    Google Scholar 

  122. Roth D, Milgrom M, Esquenazi V, Miller J (1988) Post-transplantation glucose intolerance: increased incidence in cyclosporine (Cy A) treated patients. Kidney Int 33: 450

    Google Scholar 

  123. Mejia G, Arbelaez M, Henao JE, Arango JL, Garcia A (1989) Cyclosporine-associated diabetes mellitus in renal transplants. Clin Transplant 3: 260–263

    Google Scholar 

  124. Roth D, Milgrom M, Esquenazi V, Fuller L, Burke G, Miller J (1989) Post-transplant hyperglycemia: increased incidence in cyclosporine-treated renal allograft recipients. Transplantation 47: 278–281

    Google Scholar 

  125. Boudreaux JP, McHugh L, Canafax DM, Ascher N, Sutherland DER, Payne W, Simmons RL, Najarian JS, Fryd DS (1987) The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients. Transplantation 44: 376–381

    Google Scholar 

  126. Copeland JG, Emery RW, Levinson MM, Icenogle TB, Riley JE, McAleer MJ, Copeland JA, Dietz R (1986) Cyclosporine: an immunosuppressive panacea? J Thorac Cardiovas C Surg 91: 26–39

    Google Scholar 

  127. Tapparelli C, Sanjar S, Mazzoni L, Donatsch P, Morley J (1989) In vivo platelet hyperaggregability following chronic treatment with cyclosporin A. Br J Pharmacol 97: 442P

  128. Wiesinger D, Mason J (1989) Sandimmune and platelet aggregation in vitro. Kidney Int 35: 510

    Google Scholar 

  129. Benigni A, Chiabrando C, Piccinelli A, Perico N, Gavinelli M, Furci L, Patino O, Abbate M, Bertani T, Remuzzi G, (1988) Increased urinary excretion of thromboxane B2 and 2,3-dinor-TxB2 in cyclosporin A nephrotoxicity. Kidney Int 34: 164–174

    Google Scholar 

  130. Garcia-Maldonado M, Kaufman CE, Comp PC (1990) Cyclosporine reduces thrombomodulin activity on endothelial cells. Kidney Int 37: 595

    Google Scholar 

  131. Vanrenterghem Y, Roels L, Lerut T, Gruwez J, Michielsen P, Gresele P, Deckmyn H, Colucci M, Arnout J, Vermylen J (1985) Thromboembolic complications and haemostatic changes in cyclosporin-treated cadaveric kidney allograft recipients. Lancet I: 999–1002

    Google Scholar 

  132. Grace AA, Barradas MA, Mikhailidis DP, Jeremy JY, Moorhead JF, Sweny P, Dandona P (1987) Cyclosporine A enhances platelet aggregation. Kidney Int 32: 889–895

    Google Scholar 

  133. Cohen H, Neild GH, Patel R, Mackie IJ, Machin SJ (1988) Evidence for chronic platelet hyperaggregability and in vivo activation in cyclosporin-treated renal allograft recipients. Thromb Res 49: 91–101

    Google Scholar 

  134. Scott JP, Nunez D, Reardon D, Luddington R, Folawski J, Evans DB, Higenbottam TW, Calne R (1987) Effect of cyclosporine on platelet aggregation in renal transplant recipients. Transplant Proc 19: 4008

    Google Scholar 

  135. Bernstein ZP, Robson ER, Small BM, Bettigole RE (1985) The effect of cyclosporin on platelet aggregation. Blood 66 [Suppl 1]: 300a

    Google Scholar 

  136. Jorkasky DK, Fisher CA, Stahl RF, Addonizio VP, Glickman JD (1989) The effects of cyclosporine on human platelet aggregation and thromboxane release. Transplant Proc 21: 948–949

    Google Scholar 

  137. Lawless S, Kaiser B, Polinsky M, Wagner C, Baluarte HJ (1987) Renal vein thrombosis as a complication of cyclosporine in pediatric renal transplantation. Pediatr Nephrol 1: C35

    Google Scholar 

  138. Allen RD, Michie CA, Morris PJ, Chapman JR (1985) Venous thrombosis and cyclosporin. Lancet II: 1004

    Google Scholar 

  139. Allen RDM, Michie CA, Murie JA, Morris PJ (1987) Deep venous thrombosis after renal transplantation. Surg. Gynec Obstet 164: 137–142

    Google Scholar 

  140. Bergentz SE, Bergqvist D, Bornmyr S, Brunkwall J, Husberg B (1985) Venous thrombosis and cyclosporin. Lancet I: 101–102

    Google Scholar 

  141. Brunkwall J, Bergqvist D, Bergentz SE, Bornmyr S, Husberg B (1987) Postoperative deep venous thrombosis after renal transplantation: Effects of cyclosporine. Transplantation 43: 647–649

    Google Scholar 

  142. Zazgornik J, Kopsa H, Balcke P, Minar E, Shaheen F (1985) Venous thrombosis and cyclosporin. Lancet II: 102

    Google Scholar 

  143. Leitha T, Graninger W, Zazgornik J (1988) Cyclosporine A does not increase the frequency of thromboembolic events. Transplant Proc 20 [Suppl 3]: 436–438

    Google Scholar 

  144. Jones RM, Murie JA, Ting A, Dunnill MS, Morris PJ (1988) Renal vascular thrombosis of cadaveric renal allografts in patients receiving cyclosporin, azathioprine and prednisolone triple therapy. Clin Transplant 2: 122–126

    Google Scholar 

  145. Gruber SA, Pescovitz MD, Simmons RL, Najarian JS, Ascher NL, Payne WD, Sutherland DER, Fryd DS (1987) Thromboembolic complications in renal allograft recipients. A report from the prospective randomized study of cyclosporine versus azathioprine-antilymphocyte globulin. Transplantation 44: 775–778

    Google Scholar 

  146. Bergqvist D, Bergentz SE, Bornmyr S, Husberg B, Konrad P, Ljungner H (1985) Deep vein thrombosis after renal transplantation: a prospective analysis of frequency and risk factors. Eur Surg Res 17: 69–74

    Google Scholar 

  147. Rao KV, Smith EJ, Alexander JW, Fidler JP, Pemmaraju SR, Pollack VE (1976) Thromboembolic disease in renal allograft recipients. What is its clinical significance? Arch Surg 111: 1086–1092

    Google Scholar 

  148. Gruber SA, Fryd DS, Chavers B, Canafax DM, Payne WD, Simmons RL, Najarian JS (1988) The thrombogenicity of cyclosporine. Clin Transplant 2: 99–101

    Google Scholar 

  149. Keusch G, Baumgartner D, Gmür J, Burger HR, Largiader F, Binswanger U (1985) Successful plasmapheresis for ciclosporin (Cs)-induced haemolytic uremic syndrome (HUS) in two renal allograft recipients. Kidney Int 28: 377

    Google Scholar 

  150. Wolfe JA, McCann RL, Sanfilippo F (1986) Cyclosporine-associated microangiopathy in renal transplantation: a severe but potentially reversible form of early graft injury. Transplantation 41: 541–544

    Google Scholar 

  151. Van Buren D, Van Buren CT, Flechner SM, Maddox AM, Verani R, Kahan BD (1985) De novo hemolytic uremic syndrome in renal transplant recipients immunosuppressed with cyclosporine. Surgery 98: 54–62

    Google Scholar 

  152. Berden JHM, Netten P, Liessum PA van, Hoitsma AJ, Assman KJM, Monnens LA, Koene RAP (1987) Hemolytic-uremic syndrome during cyclosporine immunosuppression in renal allograft recipients. Clin Transplant 1: 246–252

    Google Scholar 

  153. Leithner C, Sinzinger H, Pohanka E, Schwarz M, Kretschmer G, Syré G (1983) Occurrence of hemolytic uremic syndrome under cyclosporine treatment: accident or possible side-effect mediated by lack of prostacyclin-stimulating plasma factor? Transplant Proc 15: 2787–2789

    Google Scholar 

  154. Neild GH, Reuben R, Hartley B, Cameron JS (1985) Glomerular thrombi in renal allografts associated with cyclosporin treatment. Clin Pathol 38: 253–258

    Google Scholar 

  155. Sommer BG, Innes JT, Whitehurst RM, Sharma HM, Ferguson RM (1985) Cyclosporine-associated renal arteriopathy resulting in loss of allograft function. Am J Surg 149: 756–764

    Google Scholar 

  156. Bonser RS, Adu D, Franklin I, McMaster P (1984) Cyclosporin-induced haemolytic uraemic syndrome in liver allograft recipient. Lancet II: 1337

    Google Scholar 

  157. Mackenzie JC, Lumley HS, Hughes RG, Leigh M, Clink HM, Kay HEM, Powles RL (1983) Haemolytic uraemic syndrome in bone marrow transplantation. Exp Hematol 11 [Suppl 13]: 18

    Google Scholar 

  158. Shulman H, Striker G, Deeg HJ, Kennedy M, Storb R, Thomas ED (1981) Nephrotoxicity of cyclosporin A after allogeneic marrow transplantation: Glomerular thromboses and tubular injury. N Engl J Med 305: 1392–1395

    Google Scholar 

  159. Hows JM, Chipping PM, Fairhead S, Smith J, Baughan A, Gordon-Smith EC (1983) Nephrotoxicity in bone marrow transplant recipients treated with cyclosporin A. Br J Haematol 54: 69–78

    Google Scholar 

  160. Atkinson K, Biggs JC, Hayes J, Ralston M, Dodds AJ, Concannon AJ, Naidoo D (1983) Cyclosporin A associated nephrotoxicity in the first 100 days after allogeneic bone marrow transplantation: three distinct syndromes. Br J Haematol 54: 59–67

    Google Scholar 

  161. Chappell ME, Keeling DM, Prentice HG, Sweeny P (1988) Haemolytic uraemic syndrome after bone marrow transplantation: an adverse effect of total body irradiation? Bone Marrow Transplant 3: 339–347

    Google Scholar 

  162. Bergstein J, Andreoli SP, Provisor AJ, Yum M (1986) Radiation nephritis following total-body irradiation and cyclophosphamide in preparation for bone marrow transplantation. Transplantation 41: 63–66

    Google Scholar 

  163. Holler E, Kolb HJ, Gerhartz HH, Brehm G, Mraz W, Jehn U, Wilmanns W (1987) High incidence of haemolytic syndromes after allogeneic BMT-association with cyclosporin nephrotoxicity and acute GVHD. Bone Marrow Transplant 2 [Suppl 1]: 169

    Google Scholar 

  164. Marshall RJ, Sweny P (1986) Haemolytic-uraemic syndrome in recipients of bone marrow transplants not treated with cyclosporin A. Histopathology 10: 953–962

    Google Scholar 

  165. Neild GH, Ivory K, Williams DG (1984) Glomerular thrombosis and cortical infarction in cyclosporin-treated rabbits with acute serum sickness. Brit J Exp Pathol 65: 133–144

    Google Scholar 

  166. Huser B, Lämmle B, Tran TH, Oberholzer M, Thiel G, Duckert F (1984) Hämostase-Kriterien bei Nierentransplantatträgern. Vergleich zwischen Patienten unter Immunosuppression mit Ciclosporin bzw. Azathioprin/Steroiden. Schweiz Med Wochenschr 114: 1149–1154

    Google Scholar 

  167. Thomson AW, Webster LM, Aldridge RD, Morrice LM (1985) Cyclosporin and leukocyte procoagulant activity. LancetI: 1396

    Google Scholar 

  168. Carlsen E, Courillon-Mallet A, Prydz H (1985) Effect of cyclosporine A on procoagulant activity in mononuclear blood cells and monocytes in vitro. Clin Exp Immunol 60: 407–416

    Google Scholar 

  169. Huser B, Lämmle B, Landmann J, Tran TH, Oberholzer M, Thiel G, Mihatsch MJ, Duckert F (1989) Von Willebrand factor (VWF: AG) and factor VIII (VIII: C) in renal transplant recipients under immunosuppression with cyclosporine (CsA). Kidney Int 36: 317

    Google Scholar 

  170. Bartosh S, Stuart M, Baluarte HJ (1990) Von Willebrand factor (vWF) profiles in pediatric (ped) renal transplant (Tx) patients (pts) and the effect of cyclosporin (CyA). Kidney Int 37: 602

    Google Scholar 

  171. Brown Z, Neild GH, Willoughby JJ, Somia NV, Cameron SJ (1986) Increased factor VIII as an index of vascular injury in cyclosporine nephrotoxicity. Transplantation 42: 150–153

    Google Scholar 

  172. Isacson S (1970) Effect of prednisolone on the coagulation and fibrinolytic systems. Scand J Haematol 7: 212–216

    Google Scholar 

  173. Cohen H, Neild G, Mackie IJ, Machin SJ (1988) Persistent decreased fibrinolytic activity in cyclosporin-treated renal allograft recipients. Fibrinolysis 2: 197–201

    Google Scholar 

  174. Rondeau E, Peraldi MN, Villamediana LM, Ruedin P, Sraer JD (1989) Cyclosporin A (CsA) increases plasminogen activator inhibitor type 1 (PAI1) synthesis by human mesangial cells in culture (MC). Kidney Int 35: 181

    Google Scholar 

  175. Capitanio A, Mannucci PM, Ponticelli C, Pareti F (1982) Detection of circulating released platelets after renal transplantation. Transplantation 33: 298–301

    Google Scholar 

  176. Frampton G, Parbtani A, Marchesi D, Duffus P, Livio M, Remuzzi G, Cameron JS (1983) In vivo platelet activation with in vitro hyperaggregability to arachidonic acid in renal allograft recipients. Kidney Int 23: 506–513

    Google Scholar 

  177. Racusen LC, Famiglio LM, Fivush BA, Olton DS, Solez K (1988) Neurologic abnormalities and mortality in rats treated with cyclosporine A. Transplant Proc 20 [Suppl 3]: 934–936

    Google Scholar 

  178. Ryffel B, Donatsch P, Madörin M, Matter BE, Rüttimann G, Schön H, Stoll R, Wilson J (1983) Toxicological evaluation of cyclosporin A. Arch Toxicol 53: 107–141

    Google Scholar 

  179. Boland J, Atkinson K, Britton K, Darveniza P, Johnson S, Biggs J (1984) Tissue distribution and toxicity of cyclosporin A in the mouse. Pathology 16: 117–123

    Google Scholar 

  180. Christenson M, McCrindle B, Fivush B, Racusen L (1990) Cyclosporin A (CsA) lowers seizure threshold in a model of electroshock-induced seizures in rats. Kidney Int 37: 594

    Google Scholar 

  181. Martinez AJ, Puglia J (1988) The neuropathology of liver, heart, and heart-lung transplantation. Transplant Proc 20 [Suppl 1]: 806–809

    Google Scholar 

  182. Montero CG, Martinez AJ (1986) Neuropathology of heart transplantation: 23 cases. Neurology 36: 1149–1154

    Google Scholar 

  183. Boon AP, Adams DH, Carey MP, Williams A, McMaster P, Elias E (1988) Cyclosporin-associated cerebral lesions in liver transplantation. Lancet I: 1457

    Google Scholar 

  184. Starzl TE, Schneck SA, Mazzoni G, Aldrete JA, Porter KA, Schroter GP, Koep LJ, Putnam CW (1978) Acute neurological complications after liver transplantation with particular reference to intraoperative cerebral air embolus. Ann Surg 187: 236–240

    Google Scholar 

  185. Schüler S, Warnecke H, Hetzer R (1987) Prevention of toxic side effects of cyclosporine in heart transplantation. Transplant Proc 19: 2518–2521

    Google Scholar 

  186. Grigg MM, Constanzo-Nordin MR, Celesia GG, Kelly MA, Silver MA, Sobotka PA, Robinson JA (1988) The etiology of seizures after cardiac transplantation. Transplant Proc 20 [Suppl 3]: 937–944

    Google Scholar 

  187. Fricker FJ, Griffith BP, Hardesty RL, Trento A, Gold LM, Schmeltz K, Beerman LB, Fischer DR, Mathews RA, Neches WH, Park SC, Zuberbuhler JR, Lenox CC, Bahnson HT (1987) Experience with heart transplantation in children. Pediatrics 79: 138–146

    Google Scholar 

  188. Lane RJM, Roche SW, Leung AAW, Greco A, Lange LS (1988) Cyclosporin neurotoxicity in cardiac transplant recipients. J Neurol Neurosurg Psychiatry 51: 1434–1437

    Google Scholar 

  189. Adams DH, Ponsford S, Gunson B, Boon A, Honigsberger L, Williams A, Buckels J, Elias E, McMaster P, (1987)Neurological complications following liver transplantation. Lancet I: 949–951

    Google Scholar 

  190. Vogt DP, Lederman RJ, Carey WD, Broughan TA (1988) Neurologic complications of liver transplantation. Transplantation 45: 1057–1061

    Google Scholar 

  191. Groen PC de, Aksamit AJ, Rakela J, Forbes GS, Krom RAF (1987) Central nervous system toxicity after liver transplantation. The role of cyclosporine and cholesterol. N Engl J Med 317: 861–866

    Google Scholar 

  192. Powell-Jackson PR, Carmichael FJL, Calne RY, Williams R (1984) Adult respiratory distress syndrome and convulsions associated with administration of cyclosporine in liver transplant recipients. Transplantation 38: 341–343

    Google Scholar 

  193. Velu T, Debusscher L, Stryckmans PA (1985) Cyclosporin-associated fatal convulsions. Lancet I: 219

    Google Scholar 

  194. Barrett AJ, Kendra JR, Lucas CF, Joss DV, Joshi R, Pendharkar P, Hugh-Jones K (1982) Cyclosporin A as prophylaxis against graftversus-host disease in 36 patients. Br Med J 285: 162–166

    Google Scholar 

  195. Joss DV, Barrett AJ, Kendra JR, Lucas CF, Desai S (1982) Hypertension and convulsions in children receiving cyclosporin A. Lancet I: 906

    Google Scholar 

  196. Boogaerts MA, Zachee P, Verwilghen RL (1982) Cyclosporin, methylprednisolone, and convulsions. Lancet II: 1216–1217

    Google Scholar 

  197. Durrant S, Chipping PM, Palmer S, Gordon-Smith EC (1982) Cyclosporin A, methylprednisolone, and convulsions. Lancet II: 829–830

    Google Scholar 

  198. Labar B, Bogdanic V, Plavsic F, Francetic I, Dobric I, Kastelan A, Grgicevic D, Vrtar M, Grgic-Markulin L, Balabanic-Kamauf B, Boban D, Kerhin-Brkljacic V, Boranic M (1986) Cyclosporin neurotoxicity in patients treated with allogenec bone marrow transplantation. Biomed Pharmacother 40: 148–150

    Google Scholar 

  199. Thompson CB, Sullivan KM, June CH, Thomas ED (1984) Association between cyclosporin neurotoxicity and hypomagnesaemia. Lancet II: 1116–1120

    Google Scholar 

  200. Beaman M, Parvin S, Veitch PS, Walls J (1985) Convulsions associated with cyclosporin A in renal transplant recipients. Br Med J 290: 139–140

    Google Scholar 

  201. Shah D, Rylance PB, Rogerson ME, Bewick M, Parsons V (1984) Generalised epileptic fits in renal transplant recipients given cyclosporin A. Br Med J 289: 1347–1348

    Google Scholar 

  202. Najarian JS, Strand M, Fryd DS, Ferguson RM, Simmons RL, Ascher NL, Sutherland DER (1983) Comparison of cyclosporine versus azathioprine-antilymphocyte globulin in renal transplantation. Transplant Proc 15 [Suppl 1/2]: 2463–2468

    Google Scholar 

  203. The Canadian Multicentre Transplant Study Group (1983) A randomized clinical trial of cyclosporine in cadaveric renal transplantation. N Engl J Med 309: 809–815

    Google Scholar 

  204. Lavenstein B, Stewart C, Tina LU (1988) Cyclosporine-associated encephalopathy in childhood transplant patients. Transplant Proc 20 [Suppl 3]: 285–287

    Google Scholar 

  205. Graffenried B von, Krupp P (1986) Side effects of cyclosporine (Sandimmun) in renal transplant recipients and in patients with autoimmune diseases. Transplant Proc 18: 876–883

    Google Scholar 

  206. Rudge P, Koetsier JC, Mertin J, Mispelblom-Beyer J, Walbeek HK van, Jones CR, Harrison, J, Robinson K, Mellein B, Poole T, Stokvis JCJM, Timonen P (1989) Randomised double-blind controlled trial of cyclosporin in multiple sclerosis. J Neurol Neurosurg Psychiatry 52: 559–565

    Google Scholar 

  207. Kappos L, Patzold U, Dommasch D, Poser S, Haas J, Krausenec P, Malin JP, Fierz W, Graffenried B von, Gugerli US (1988) Cyclosporine versus azathioprine in the long-term treatment of multiple sclerosis. Results of the German Multicenter Study. Ann Neurol 23: 56–63

    Google Scholar 

  208. Vellodi A, Jayatunga, R, Hugh-Jones K (1987) Hemiplegia and focal convulsions as a manifestation of cyclosporine A toxicity. J Clin Pharmacol 27: 914–915

    Google Scholar 

  209. Appleton RE, Farrell K, Teal P, Hashimoto SA, Wong PKH (1989) Complex partial status epilepticus associated with cyclosporin A therapy. J Neurol Neurosurg Psychiatr 52: 1068–1071

    Google Scholar 

  210. Rubin AM, Kang H (1987) Cerebral blindness and encephalopathy with cyclosporin A toxicity. Neurology 37: 1072–1076

    Google Scholar 

  211. O'Connor JP, Kleinman DS, Kunze HE (1985) Hypomagnesaemia and cyclosporin toxicity. Lancet I: 104–105

    Google Scholar 

  212. Wilczek H, Ringden O, Tyden G (1985) Cyclosporine-associated central nervous system toxicity after renal transplantation. Transplantation 39: 110

    Google Scholar 

  213. Berden JHM, Hoitsma AJ, Merx JL, Keyser A (1985) Severe central-nervous-system toxicity associated with cyclosporin. Lancet I: 219–220

    Google Scholar 

  214. Katirji MB (1987) Visual hallucinations and cyclosporine. Transplantation 43: 768–769

    Google Scholar 

  215. Atkinson K, Biggs J, Darveniza P, Boland J, Concannon A, Dodds A (1984) Cyclosporine-associated central nervous system toxicity after allogeneic bone marrow transplantation. Transplantation 38: 34–37

    Google Scholar 

  216. Noll RB, Kulkarni R (1984) Complex visual hallucinations and cyclosporine. Arch Neurol 41: 329–330

    Google Scholar 

  217. Cockburn I, Götz E, Gülich A, Krupp P (1988) An interim analysis of the on-going long-term safety study of cyclosporine in renal transplantation. Transplant Proc 20 [Suppl 3]: 519–529

    Google Scholar 

  218. Von Graffenried B (1989) Sandimmun® (cyclosporin) in autoimmune diseases. Overview on early clinical experience (status September 1987). Am J Nephrol 9 [Suppl 1]: 51–56

    Google Scholar 

  219. Palestine AG, Nussenblatt RB, Chan CC (1984) Side effects of systemic cyclosporine in patients not undergoing transplantation. Am J Med 77: 652–656

    Google Scholar 

  220. Gross MLP, Sweny P, Pearson RM, Kennedy J, Fernando ON, Moorhead JF (1982) Rejection encephalopathy. An acute neurological syndrome complicating renal transplantation. J Neurol Sci 56: 23–34

    Google Scholar 

  221. Lampe EW, Simmons RL, Najarian JS (1972) Hyperglycemic non-ketotic coma after liver transplantation. Arch Surg 105: 774–776

    Google Scholar 

  222. Nordal KP, Talseth T, Dahl E, Attramadal A, Albrechtsen D, Halse J, Brodwall EK, Flatmark A (1985) Aluminium overload, a predisposing condition for epileptic seizures in renal transplant patients treated with cyclosporine? Lancet II: 153–154

    Google Scholar 

  223. Loughran TP, Deeg HJ, Dahlberg S, Kennedy MS, Storb R, Thomas ED (1985) Incidence of hypertension after marrow transplantation among 112 patients randomized to either cyclosporine or methotrexate as graft-versus-host disease prophylaxis. Br J Haematol 59: 547–553

    Google Scholar 

  224. Juan D (1982) Clinical review: the clinical importance of hypomagnesemia. Surgery 91: 510–517

    Google Scholar 

  225. Fishman RA (1965) Neurological aspects of magnesium metabolism. Arch Neurol 12: 562–569

    Google Scholar 

  226. Cockburn I, Krupp P (1989) An appraisal of drug interactions with Sandimmun® Transplant Proc 21: 3845–3850

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Sandimmune is the registered trademark for cyclosporine

Part I of this survey is published in Pediatr Nephrol (1990) 4: 554–574

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mason, J. The pathophysiology of sandimmune (cyclosporine) in man and animals. Pediatr Nephrol 4, 686–704 (1990). https://doi.org/10.1007/BF00858649

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00858649

Key words

Navigation