Skip to main content
SpringerLink
Log in

Cyclosporin-Induced Hypertension

Incidence, Pathogenesis and Management

  • Review Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Blood pressure increases soon after administration of immunosuppressive regimens using cyclosporin. Characteristic vascular changes lead to systemic and renal vasoconstriction. Changes in blood pressure are commonly associated with disturbed circadian regulation and may promote the rapid development of target organ injury, including intracranial haemorrhage, left ventricular hypertrophy and microangiopathic haemolysis. The mechanisms underlying this disorder are complex and include altered vascular endothelial function. Vasodilators such as pro-stacyclin and nitric oxide are suppressed, whereas vasoconstrictors, including endothelin, are increased. Changes in the kidney include vasoconstriction, reduced glomerular filtration and sodium retention. Effective therapy depends upon rigorous blood pressure control by administration of vasodilating agents, with attention to potential interactions with cyclosporin.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Faulds D, Goa KL, Benfield P. Cyclosporin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs 1993; 45: 953–1040

    Article  PubMed  CAS  Google Scholar 

  2. Bennett WM, Pulliam JP. Cyclosporine nephrotoxicity. Ann Int Med 1983; 99(6): 851–4

    PubMed  CAS  Google Scholar 

  3. Porter GA, Bennett WM, Sheps SG. Cyclosporine-associated hypertension: National High Blood Pressure Education Program. Arch Int Med 1990; 150: 280–3

    Article  CAS  Google Scholar 

  4. The U.S. Multicenter FK506 Liver Study Group. A comparison of tacrolimus (FK507) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med 1994; 331: 1110–5

    Article  Google Scholar 

  5. Textor SC, Wiesner R, Wilson DJ, et al. Systemic and renal hemodynamic differences between FK506 and cyclosporine A in liver transplant recipients. Transplantation 1993; 55: 1332–9

    Article  PubMed  CAS  Google Scholar 

  6. Taler SJ, Textor SC, Canzanello VJ, et al. Role of steroid dose in hypertension early after liver transplantation with tacrolimus (FK506) and cyclosporine. Transplantation 1996; 62: 1588–92

    Article  PubMed  CAS  Google Scholar 

  7. Textor SC, Canzanello VJ, Taler SJ, et al. Cyclosporine-induced hypertension after transplantation. Mayo Clin Proc 1994; 69: 1182–93

    PubMed  CAS  Google Scholar 

  8. Powles AV, McFadden JP, Baker BS, et al. Reversibility of renal function of patients on long-term cyclosporin for psoriasis. Br J Dermatol 1989; 123 Suppl. 34: 19

    Google Scholar 

  9. Hollander AAMJ, Hene RJ, Hermans J, et al. Late Prednisone withdrawal in cyclosporine-treated kidney transplant patients: a randomized study. J Am Soc Nephrol 1997; 8: 294–301

    PubMed  CAS  Google Scholar 

  10. Hricik DE, Lautman J, Bartucci MR, et al. Variable effects of steroid withdrawal on blood pressure reduction in cyclosporine-treated renal transplant recipients. Transplantation 1992; 53: 1232–5

    Article  PubMed  CAS  Google Scholar 

  11. Sturrock NDC, Lang CC, Struthers AD. Cyclosporin-induced hypertension precedes renal dysfunction and sodium retention in man. J Hypertens 1993; 11: 1209–16

    Article  PubMed  CAS  Google Scholar 

  12. Reeves RA, Shapiro AP, Thompson ME, et al. Loss of nocturnal decline in blood pressure after cardiac transplantation. Circulation 1986; 73: 401–8

    Article  PubMed  CAS  Google Scholar 

  13. Wenting GJ, van den Meiracker AH, van Eck HJR, et al. Lack of circadian variation of blood pressure after heart transplantation. J Hypertens 1986; 4 Suppl.: S78–80

    Google Scholar 

  14. Taler SJ, Textor SC, Canzanello VJ, et al. Loss of nocturnal blood pressure fall after liver transplantation during immunosuppressive therapy. Am J Hypertens 1995; 8: 598–605

    Article  PubMed  CAS  Google Scholar 

  15. Idema RN, van den Meiracker AH, Balk AH, et al. Abnormal diurnal variation of blood pressure, cardiac output and vascular resistance in cardiac transplant recipients. Circulation 1994; 90: 2797–803

    Article  PubMed  CAS  Google Scholar 

  16. Verdecchia P, Schillaci G, Guerrieri M, et al. Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 1990; 81: 528–36

    Article  PubMed  CAS  Google Scholar 

  17. Shimada K, Kaxamoto A, Matsubayashi K, et.al. Diurnal blood pressure variations and silent cerebrovascular damage in elderly patients with hypertension. JHypertens 1992; 10: 875–8

    CAS  Google Scholar 

  18. Bianchi S, Bigazzi R, Baldari G, et al. Diurnal variations of blood pressure and microalbuminuria in essential hypertension. Am J Hypertens 1994; 7: 23–9

    PubMed  CAS  Google Scholar 

  19. van de Borne P, Leeman M, Primo G, Degaute JP. Reappearance of a normal circadian rhythm of blood pressure after cardiac transplantation. Am J Cardiol 1992; 69: 794–801

    Article  PubMed  Google Scholar 

  20. von Polnitz A, Bracht C, Kemkes B, et al. Circadian pattern of blood pressure and heart rate in the longer term after heart transplantation. J Cardiovasc Pharmacol 1990; 16 Suppl.: S86–9

    Google Scholar 

  21. Imai Y, Abe K, Sasaki S, et al. Exogenous glucocorticoid eliminates or reverses circadian blood pressure variations. J Hypertens 1989; 7: 113–20

    PubMed  CAS  Google Scholar 

  22. Imai Y, Abe K, Sasaki S, et al. Altered circadian blood pressure rhythm in patients with Cushing’s syndrome. Hypertension 1988; 12: 11–9

    Article  PubMed  CAS  Google Scholar 

  23. Luke RG. Mechanism of Cyclosporine-induced hypertension. Am J Hypertens 1991; 4: 468–71

    PubMed  CAS  Google Scholar 

  24. Singer DRJ, Markandu RGN, Buckley MG, et al. Blood pressure and endocrine responses to changes in dietary sodium intake in cardiac transplant recipients: implications for the control of sodium balance. Circulation 1994; 89: 1153–9

    Article  PubMed  CAS  Google Scholar 

  25. Andoh TF, Burdmann EA, Bennett WM. Nephrotoxicity of immunosuppressive drugs: experimental and clinical observations. Semin Nephral 1997; 17: 34–45

    CAS  Google Scholar 

  26. Whitworth JA. Renal parenchymal disease and hypertension. In: Robertson US, editor. Clinical hypertension. Amsterdam: Elsevier, 1992; 326–50

    Google Scholar 

  27. Kasiske BL, Guijarro C, Massy ZA, et al. Cardiovascular disease after renal transplantation. J Am Soc Nephrol 1996; 7: 158–65

    PubMed  CAS  Google Scholar 

  28. Ballentyne CM, Bourge RC, Domalik LJ, et al. Treatment of hyperlipidemia after heart transplantation and rational for the Heart Transplant Lipid Registry. Am J Cardiol 1996; 78: 766–71

    Google Scholar 

  29. Schwartz L, Augustine J, Raymer J, et al. Nurse management of posttransplant hypertension in liver transplant patients. J Transplant 1996; 6: 139–44

    CAS  Google Scholar 

  30. Hilbrands LB, Hoitsma AJ, van Hamersvelt HW, et al. Acute effects of nifedipine in renal transplant recipients treated with cyclosporine or azathioprine. Am J Kidney Dis 1994; 24: 838–45

    PubMed  CAS  Google Scholar 

  31. Textor SC. De-novo hypertension after liver transplantation. Hypertension 1993; 22: 257–67

    Article  PubMed  CAS  Google Scholar 

  32. Textor SC, Wilson DJ, Lerman A, et al. Renal hemodynamics, urinary eicosanoids, and endothelin after liver transplantation. Transplantation 1992; 54: 74–80

    Article  PubMed  CAS  Google Scholar 

  33. Bantle JP, Boudreau RJ, Ferris TF. Suppression of plasma renin activity by cyclosporine. Am J Med 1987; 83: 59–64

    Article  PubMed  CAS  Google Scholar 

  34. Textor SC, Forman SJ, Bravo EL, et al. De-Novo accelerated hypertension during sequential cyclosporine and Prednisone therapy in normotensive bone marrow transplant recipients. Transplant Proc 1988; 20 Suppl. 3: 480–6

    PubMed  CAS  Google Scholar 

  35. Moss NG, Powell SL, Falk RJ. Intravenous cyclosporine activates afferent and efferent renal nerves and causes sodium retention in innervated kidneys in rats. Proc Natl Acad Sci U S A 1985; 82: 8222–6

    Article  PubMed  CAS  Google Scholar 

  36. Sander M, Victor RG. Hypertension after cardiac transplantation: pathophysiology and management. Curr Opin Nephrol Hypertension 1995; 4: 443–51

    Article  CAS  Google Scholar 

  37. Kaye D, Thompson J, Jennings G, et al. Cyclosporine therapy after cardiac transplantation causes hypertension and renal vasoconstriction without sympathetic activation. Circulation 1993; 88: 1101–9

    Article  PubMed  CAS  Google Scholar 

  38. Floras JS, Legault L, Morali GA, et al. Increased sympathetic outflow in cirrhosis and ascites: direct evidence from intraneural recordings. Ann Intern Med 1991; 114: 373–80

    PubMed  CAS  Google Scholar 

  39. Deray G, Carayon A, Le Hoang P. Increased endothelin level after cyclosporine therapy [letter]. Ann Int Med 1991; 114: 809

    PubMed  CAS  Google Scholar 

  40. Textor SC, Burnett JC, Romero JC, et al. Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation. Kidney Int 1995; 47: 1426–33

    Article  PubMed  CAS  Google Scholar 

  41. Bartholomeusz B, Hardy KJ, Nelson AS, et al. Bosentan ameliorates cyclosporin A-induced hypertension in rats and primates. Hypertension 1996; 27: 1341–5

    Article  PubMed  CAS  Google Scholar 

  42. Lanese DM, Conger JD. Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles. J Clin Invest 1993; 91: 2144–9

    Article  PubMed  CAS  Google Scholar 

  43. Lerman A, Sandok EK, Hildebrand FL, et al. Inhibition of endothelium-derived relaxing factor enhances endothelin-mediated vasoconstriction. Circulation 1992; 85: 1894–8

    Article  PubMed  CAS  Google Scholar 

  44. Perico N, Ruggenenti P, Gaspari F, et al. Daily renal hypoperfusion induced by cyclosporine in patients with renal transplantation. Transplantation 1992; 54: 56–60

    Article  PubMed  CAS  Google Scholar 

  45. Smith SR, Creech EA, Schaffer AV, et al. Effects of thromboxane synthase inhibition with CGS 13080 in human cyclosporine nephrotoxicity. Kidney Int 1992; 41: 199–205

    Article  PubMed  CAS  Google Scholar 

  46. Homan van der Heide JJ, Bilo HJG, Donker JM, et al. Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants. N Engl J Med 1993; 329: 769–73

    Article  Google Scholar 

  47. Ventura HO, Milani RV, Lavie CJ, et al. Cyclosporine-induced hypertension: efficacy of omega-3 fatty acids in patients after cardiac transplantation. Circulation 1993; 88(2): 11281–5

    Google Scholar 

  48. Perico N, Benigni A, Zoya C, et al. Functional significance of exaggerated renal thromboxane A2 synthesis induced by cyclosporin A. Am J Physiol 1986; 20: F81–7

    Google Scholar 

  49. Coffman TM, Care DR, Yarger WE, et al. Evidence that renal Prostaglandin and thromboxane production is stimulated in chronic cyclosporine. Transplantation 1987; 43: 282–5

    Article  PubMed  CAS  Google Scholar 

  50. Petric R, Freeman D, Wallace C, et al. Effect of cyclosporine on urinary Prostanoid excretion, renal blood flow, and glomerulotubular function. Transplantation 1988; 45: 883–9

    Article  PubMed  CAS  Google Scholar 

  51. Koivisto VA, Leirisalo-Repo M, Pelkonen R, et al. Cyclosporin reduces renal Prostanoid excretion in type I diabetic patients. Acta Diabetologica 1992; 29: 1–5

    Article  PubMed  CAS  Google Scholar 

  52. Conte G, Dal Canton A, Sabbatini M, et al. Acute cyclosporine dysfunction reversed by dopamine infusion in healthy subjects. Kidney Int 1989; 36: 1086–92

    Article  PubMed  CAS  Google Scholar 

  53. Gaston RS, Schlessinger SD, Sanders PW, et al. Cyclosporine inhibits the renal response to L-arginine in human kidney transplant recipients. J Am Soc Nephrol 1995; 5: 1426–33

    PubMed  CAS  Google Scholar 

  54. Richards NT, Poston L, Hilston PJ. Cyclosporin A inhibits endothelium-dependent, prostanoid-induced relaxation in human subcutaneous resistance vessels. J Hypertens 1990; 8: 159–63

    Article  PubMed  CAS  Google Scholar 

  55. Duvoux C, Cherqui D, Di Martino V, et al. Nicardipine as antihypertensive therapy in liver transplant recipients: results of long-term use. Hepatology 1997; 25: 430–3

    Article  PubMed  CAS  Google Scholar 

  56. Sennesael J, Lamote J, Violet I, et al. Comparison of Perindopril and amlodipine in cyclosporine-treated renal allograft recipients. Hypertension 1995; 26: 436–44

    Article  PubMed  CAS  Google Scholar 

  57. Toupance O, Lavoud S, Canivet E, et al. Antihypertensive effect of amlodipine and lack of interference with cyclosporine metabolism in renal transplant recipients. Hypertension 1994; 24: 297–300

    Article  PubMed  CAS  Google Scholar 

  58. Pesavento TE, Jones PA, Julian BA, et al. Amlodipine increases cyclosporine levels in hypertensive renal transplant patients: results of a prospective study. J Am Soc Nephrol 1996; 7: 831–5

    PubMed  CAS  Google Scholar 

  59. van den Dorpel MA, Zietse R, Ijzermans JN, et al. Effect of isradipine on cyclosporin Arelated hypertension. Blood Press 1994; 1: 50–3

    Google Scholar 

  60. Textor SC, Schwartz L, Wilson DJ, et al. Systemic and renal effects of nifedipine in cyclosporine-associated hypertension. Hypertension 1994; 23 Suppl. I: I220–I4

    Article  PubMed  CAS  Google Scholar 

  61. Brozena SC, Johnson MR, Ventura H, et al. Effectiveness and safety of diltiazem or lisinopril in treatment of hypertension after heart transplantation. J Am Coll Cardiol 1996; 27: 1707–12

    Article  PubMed  CAS  Google Scholar 

  62. Charnick SB, Nedelman JR, Chang C-T, et al. Description of blood pressure changes in patients beginning cyclosporin A therapy. Ther Drug Monit 1997; 19: 17–24

    Article  PubMed  CAS  Google Scholar 

  63. Neumayer HH, Kunzendorf U, Schreiber M. Protective effects of calcium antagonists in human renal transplantation. Kidney Int 1992; 41 Suppl. 36: 87–93s

    Google Scholar 

  64. Harper SJ, Moorhouse, Abrams, et al. The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients — a randomised prospective study. Transplant Int 1996; 9: 115–25

    Article  CAS  Google Scholar 

  65. Dawidson I, Rooth P, Fry WR. Prevention of acute cyclosporine-induced renal blood flow inhibition and improved immunosuppression with Verapamil. Transplantation 1989; 48: 575–80

    PubMed  CAS  Google Scholar 

  66. Schroeder JS, Gao SZ, Alderman EL, et al. Apreliminary study of diltiazem in the prevention of coronary artery disease in heart-transplant recipients. NEJM 1993; 328: 164–70

    Article  PubMed  CAS  Google Scholar 

  67. Pedersen EB, Madsen JK, Sorensen SS, et al. Improvement in renal function by felodipine during cyclosporine treatment in acute and short-term studies. Kidney Int 1996; 49: s–94–6

    Google Scholar 

  68. Ahmed K, Michael B, Burke JF. Effects of isradipine on renal hemodynamics in renal transplant patients treated with cyclosporine. Clin Nephral 1997; 48: 307–10

    CAS  Google Scholar 

  69. Shin GT, Cheigh JS, Riggio RR, et al. Long-term beneficial effects of a nifedipine-supplemented immunosuppressive regimen in kidney transplantation. Transplant Proc 1996; 28: 1309–10

    PubMed  CAS  Google Scholar 

  70. Andreassen AK, Hartmann A, Offstad J, et al. Hypertension prophylaxis with omega-3 fatty acids in heart transplant recipients. J Am Coll Cardiol 1997; 29: 1324–31

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hypertension and Internal Medicine, Desk W9A, Mayo Clinic, Rochester, Minnesota, 55905, USA

    Sandra J. Taler, Stephen C. Textor, Vincent J. Canzanello & Lora Schwartz

Authors
  1. Sandra J. Taler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen C. Textor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vincent J. Canzanello
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lora Schwartz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taler, S.J., Textor, S.C., Canzanello, V.J. et al. Cyclosporin-Induced Hypertension. Drug-Safety 20, 437–449 (1999). https://doi.org/10.2165/00002018-199920050-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199920050-00004

Keywords

Search

Navigation