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Drug Therapy in Transplant Recipients

Special Considerations in the Elderly with Comorbid Conditions

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Abstract

Elderly patients with end-stage organ failure are now more frequently undergoing transplantation. Medication management in this population is challenging because of the combination of multiple comorbidities, polypharmacy, and immunological, pharmacokinetic and pharmacodynamic changes attributable to the aging process. Immunosuppressive medications can exacerbate pre-existing medical conditions and promote the development of disease processes.

Cardiovascular disorders, such as hypertension, coronary artery disease, congestive heart failure and arrhythmias are common in elderly transplant recipients, and account for most of the deaths in this population. Blood pressure, blood glucose and cholesterol control is of particular concern because elderly transplant recipients frequently have or develop these complications. Elderly transplant recipients are commonly receiving anticoagulation therapy with warfarin and are at a higher risk of bleeding, especially if they have renal dysfunction.

Infectious complications occur frequently in the transplanted population, with pneumonia being the most common infection seen in hospitalised patients. Attention to vaccination for the prevention of influenza and pneumococcal infections is important because of the increased risk of these diseases in this population. Depression itself has been associated with decreased survival in older individuals, and depression in elderly transplant recipients may be reversible with the administration of pharmacological agents.

Effective long-term care of transplant recipients demands an understanding of how particular medications affect clinical evaluation and treatment. This article addresses some of the practical issues surrounding medication management and prevention of these particular problems in elderly transplant recipients.

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References

  1. Kinsella K, Velkoff VA, US Census Bureau. An aging world: 2001. Washington, DC: US Government Printing Office; 2001 Nov. Series P95/01-1

    Google Scholar 

  2. Kendrick E. Cardiovascular disease and the renal transplant recipient. Am J Kidney Dis 2001; 38: S36–43

    PubMed  CAS  Google Scholar 

  3. Cameron JS. Renal transplantation in the elderly. Int Urol Nephrol 2000; 32: 193–201

    PubMed  CAS  Google Scholar 

  4. Smith CM, Davies DB, McBride MA. Liver transplantation in the United States: a report from the UNOS Liver Transplant Registry. Clin Transpl 1999, 23–34

    Google Scholar 

  5. Garcia CE, Garcia RFL, Mayer AD, et al. Liver transplantation in patients over sixty years of age. Transplantation 2001; 72: 679–84

    PubMed  CAS  Google Scholar 

  6. Keck BM, Bennett LE, Rosendale J, et al. Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT International Registry for Thoracic Organ Transplantation. Clin Transpl 1999, 35–49

    Google Scholar 

  7. Ali Raza J, Movahed A. Use of cardiovascular medications in the elderly. Int J Cardiol 2002 Oct; 85(2–3): 203–15

    PubMed  Google Scholar 

  8. Azad N, Tierney M, Victor G, et al. Adverse drug events in the elderly population admitted to a tertiary care hospital. J Healthc Manag 2002; 47: 295–305

    PubMed  Google Scholar 

  9. Bia MJ. Geriatric issues in renal transplantation. Geriatr Nephrol Urol 1999; 9: 109–13

    PubMed  CAS  Google Scholar 

  10. Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist 2000; 5: 224–37

    PubMed  CAS  Google Scholar 

  11. Balducci L, Stanta G. Cancer in the frail patient: a coming epidemic. Hematol Oncol Clin North Am 2000; 14: 235–50

    PubMed  CAS  Google Scholar 

  12. British National Formulary. Ciclosporin. Vol. 46. London: The Pharmaceutical Press, 2003

    Google Scholar 

  13. British National Formulary. Tacrolimus. Vol. 46. London: The Pharmaceutical Press, 2003

    Google Scholar 

  14. Schaubel D, Desmeules M, Mao Y, et al. Survival experience among elderly end-stage renal disease patients: a controlled comparison of transplantation and dialysis. Transplant 1995; 60: 1389–94

    CAS  Google Scholar 

  15. Kasiske BL, Snyder J, Matas A, et al. The impact of transplantation on survival with kidney failure. Clin Transpl 2000, 135–43

    Google Scholar 

  16. Meier-Kriesche HU, Kaplan B. Immunosuppression in elderly renal transplant recipients: are current regimens too aggressive? Drugs Aging 2001; 18: 751–9

    PubMed  CAS  Google Scholar 

  17. Rao VK. Kidney transplantation in older patients: risks and benefits. Drugs Aging 2002; 19(2): 79–84

    PubMed  Google Scholar 

  18. Kappes U, Schanz G, Gerhardt U, et al. Influence of age on the prognosis of renal transplant recipients. Am J Nephrol 2001; 21: 259–63

    PubMed  CAS  Google Scholar 

  19. De Fijter JW, Mallat MJK, Doxiadis IIN, et al. Increased immunogenicity and cause of graft loss of old donor kidneys. J Am Soc Nephrol 2001; 12: 1538–46

    PubMed  Google Scholar 

  20. Grinyó JM. Borderline kidney graft donors: what are the problems? Nephrol Dial Transplant 2000; 15: 950–2

    PubMed  Google Scholar 

  21. Basar H, Soran A, Shapiro R, et al. Renal transplantation in recipients over the age of 60: the impact of donor age. Transplantation 1999; 67: 1191–3

    PubMed  CAS  Google Scholar 

  22. Verran DJ, de Leon C, Chui AK, et al. Factors in older cadaveric organ donors impacting on renal allograft outcome. Clin Transpl 2001; 15: 1–5

    CAS  Google Scholar 

  23. Carter JT, Lee CM, Weinstein RJ, et al. Evaluation of the older cadaveric kidney donor: the impact of donor hypertension and creatinine clearance on graft performance and survival. Transplantation 2000; 70: 765–71

    PubMed  CAS  Google Scholar 

  24. Andres A, Morales JM, Herrero JC, et al. Double versus single renal allografts from aged donors. Transplantation 2000; 69: 2060–6

    PubMed  CAS  Google Scholar 

  25. Tullius SG, Reutzel-Selke A, Egermann F, et al. Contribution of prolonged ischemia and donor age to chronic renal allograft dysfunction. J Am Soc Nephrol 2000; 11: 1317–24

    PubMed  CAS  Google Scholar 

  26. Levy MF, Somasundar PS, Jennings LW, et al. The elderly liver transplant recipient: a call for caution. Ann Surg 2001 Jan; 233(1): 107–13

    PubMed  CAS  Google Scholar 

  27. Hosenpud JD, Bennett LE, Keck BM, et al. The Registry of the International Society for Heart and Lung Transplantation: 18th official report, 2001. J Heart Lung Transplant 2001 Aug; 20(8): 805–15

    PubMed  CAS  Google Scholar 

  28. Morgan JA, John R, Weinberg AD, et al. Long-term results of cardiac transplantation in patients 65 years of age and older: a comparative analysis. Ann Thorac Surg 2003 Dec; 76(6): 1982–7

    PubMed  Google Scholar 

  29. Borkon AM, Muehlebach GF, Jones PG, et al. An analysis of the effect of age on survival after heart transplant. J Heart Lung Transplant 1999; 18: 668–74

    PubMed  CAS  Google Scholar 

  30. Becker BN, Ismail N, Becker YT, et al. Renal transplantation in the older end stage renal disease patient. Semin Nephrol 1996; 16: 353–62

    PubMed  CAS  Google Scholar 

  31. Bradley BA. Rejection and recipient age. Transpl Immunol 2002; 10: 125–32

    PubMed  CAS  Google Scholar 

  32. Pahlavani MA, Harris MD, Richardson A. Activation of p21ras/MAPK signal transduction molecules decreases with age in mitogen-stimulated T cells from rats. Cell Immunol 1998; 185: 39–48

    PubMed  CAS  Google Scholar 

  33. Gillis S, Kozak R, Durante M. Immunological studies of aging: decreased production of and response to T cell growth factor by lymphocytes from aged humans. J Clin Invest 1981; 67: 937–42

    PubMed  CAS  Google Scholar 

  34. Fulop Jr T, Leblanc C, Lacombe G. Cellular distribution of protein kinase C isozymes in CD3-mediated stimulation of human T lymphocytes with aging. FEBS Lett 1995; 375: 69–74

    PubMed  CAS  Google Scholar 

  35. Bach MA. Influence of aging on T-cell subpopulations involved in the in-vitro generation of allogeneic cytotoxicity. Clin Immunol Immunopathol 1979; 13: 220–30

    PubMed  CAS  Google Scholar 

  36. Bach MA. Lymphocyte-mediated cytotoxicity: effects of ageing, adult thymectomy and thymic factor. J Immunol 1977; 119: 641–7

    PubMed  CAS  Google Scholar 

  37. Whisler RL, Liu B, Wu LC. Reduced activation of transcriptional factor AP-1 among peripheral blood T cells from elderly humans after PHA stimulation: restorative effect of phorbol diesters. Cell Immunol 1993; 152: 96–109

    PubMed  CAS  Google Scholar 

  38. Fagiolo U, Amadori A, Biselli R. Quantitative and qualitative analysis of anti-tetanus toxoid antibody response in the elderly: humoral immune response enhancement by thymostimulin. Vaccine 1993; 11: 336–40

    Google Scholar 

  39. Palomar R, Ruiz JC, Cotorruelo JG, et al. Effect of recipient age on the clinical course of renal transplantation. Nefrologia 2001; 21: 386–91

    PubMed  CAS  Google Scholar 

  40. Pehourcq F, Molimard M. Pharmacokinetics in the elderly. Rev Mal Respir 2002 Jun; 19(3): 356–62

    PubMed  CAS  Google Scholar 

  41. O’Mahony D, O’Leary P, Quigley EM. Aging and intestinal motility: a review of factors that affect intestinal motility in the aged. Drugs Aging 2002; 19: 515–27

    PubMed  Google Scholar 

  42. Schmucker DL. Liver function and phase I drug metabolism in the elderly: a paradox. Drugs Aging 2001: 18(11); 837–51

    PubMed  CAS  Google Scholar 

  43. Zeeh J, Platt D. The aging liver: structural and functional changes and their consequences for drug treatment in old age. Gerontology 2002; 48: 121–7

    PubMed  CAS  Google Scholar 

  44. Meier-Kriesche HU, Friedman G, Jacobs M, et al. Infectious complications in geriatric renal transplant patients: comparison of two immunosuppressive protocols. Transplantation 1999; 68: 1496–502

    PubMed  CAS  Google Scholar 

  45. Kasiske BL. Epidemiology of cardiovascular disease after renal transplantation. Transplantation 2001; 72: S5–8

    PubMed  CAS  Google Scholar 

  46. Schmidt A, Stefenelli T, Schuster E, et al. Informational contribution of noninvasive screening tests for coronary artery disease in patients on chronic renal replacement therapy. Am J Kidney Dis 2001; 37: 56–63

    PubMed  CAS  Google Scholar 

  47. Bundgaard H, Boesgaard S, Mortensen SA. Effect of nitroglycerin in patients with increased pulmonary vascular resistance undergoing cardiac transplantation. Scand Cardiovasc J 1997; 31(6): 339–42

    PubMed  CAS  Google Scholar 

  48. Jones TE, Morris RG. Pharmacokinetic interaction between tacrolimus and diltiazem: dose-response relationship in kidney and liver transplant recipients. Clin Pharmacokinet 2002; 41(5): 381–8

    PubMed  CAS  Google Scholar 

  49. Sketris IS, Methot ME, Nicol D, et al. Effect of calciumchannel blockers on cyclosporine clearance and use in renal transplant patients. Ann Pharmacother 1994 Nov; 28(11): 1227–31

    PubMed  CAS  Google Scholar 

  50. Hebert MF, Lam AY. Diltiazem increases tacrolimus concentrations. Ann Pharmacother 1999 Jun; 33(6): 680–2

    PubMed  CAS  Google Scholar 

  51. Brockmoller J, Neumayer HH, Wagner K, et al. Pharmacokinetic interaction between cyclosporin and diltiazem. Eur J Clin Pharmacol 1990; 38(3): 237–42

    PubMed  CAS  Google Scholar 

  52. Waldo AL. Long-term pharmacologic management of atrial fibrillation in the elderly. Am J Geriatr Cardiol 2002; 11: 233–44

    PubMed  Google Scholar 

  53. Singh SN, Lewis HD, Fisher SG, et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. N Engl J Med 1995; 333: 77–82

    PubMed  CAS  Google Scholar 

  54. Morrissey PE, Ramirez PJ, Gohh RY, et al. Management of thrombophilia in renal transplant patients. Am J Transplant 2002 Oct; 2(9): 872–6

    PubMed  Google Scholar 

  55. Friedman GS, Meier-Kriesche HU, Kaplan B, et al. Hypercoagulable states in renal transplant candidates: impact of anticoagulation upon incidence of renal allograft thrombosis. Transplantation 2001 Sep; 72(6): 1073–8

    PubMed  CAS  Google Scholar 

  56. Morris CD, Vega JD, Levy JH, et al. Warfarin therapy does not increase bleeding in patients undergoing heart transplantation. Ann Thorac Surg 2001 Sep; 72(3): 714–8

    PubMed  CAS  Google Scholar 

  57. Go AS, Hylek EM, Phillips KA, et al., for the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention. JAMA 2001; 285: 2370–5

    PubMed  CAS  Google Scholar 

  58. Feinberg WM, Blackshear JL, Laupacis A, et al. Prevalence, age distribution, and gender of patients with atrial fibrillation: analysis and implications. Arch Intern Med 1995; 155: 469–47

    PubMed  CAS  Google Scholar 

  59. Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002; 346: 1773–80

    PubMed  CAS  Google Scholar 

  60. Serruys PW, de Feyter PJ, Benghozi R, et al. The Lescol® Intervention Prevention Study (LIPS): a double blind, placebo-controlled, randomized trial of the long term effects of fluvastatin after successful transcatheter therapy in patients with coronary heart disease. Int J Cardiovasc Intervent 2001; 4: 165–72

    PubMed  Google Scholar 

  61. Reddy VS, Chen AC, Johnson HK, et al. Cardiac surgery after renal transplantation. Am Surg 2002; 68: 154–8

    PubMed  Google Scholar 

  62. Sander GE. High blood pressure in the geriatric population: treatment considerations. Am J Geriatr Cardiol 2002; 11: 223–32

    PubMed  CAS  Google Scholar 

  63. Cohen D, Galbraith C. General health management and long-term care of the renal transplant recipient. Am J Kidney Dis 2001; 38: S10–24

    PubMed  CAS  Google Scholar 

  64. Rahn KH, Barenbrock M, Fritschka E, et al. Effect of nitrendipine on renal function in renal-transplant patients treated with cyclosporin: a randomised trial. Lancet 2002; 354: 1415–20

    Google Scholar 

  65. Manske CL. Cardiovascular disease after renal transplantation: epidemiology and therapeutic strategies [letter]. Transpl Immunol 2001; 17(3): 4–12

    Google Scholar 

  66. Murphy SW, Foley RN, Parfrey PS. Screening and treatment for cardiovascular disease in patients with chronic renal disease. Am J Kid Dis 1998; 32 (5 Suppl. 3): S184–99

    PubMed  CAS  Google Scholar 

  67. Kasiske BL, Vazquez MA, Harmon WE, et al. Recommendations for the outpatient surveillance of renal transplant recipients. J Am Soc Nephrol 2000; 11: S1–S86

    PubMed  Google Scholar 

  68. Paton RR, Kane RE. Long-term diuretic therapy with metolazone of renal failure and the nephritic syndrome. J Clin Pharm 1977; 17: 243–51

    CAS  Google Scholar 

  69. Molnar GW, Read RC, Wright FE. Propanolol enhancement of hypoglycemic sweating. Clin Pharmacol Ther 1974; 15: 490–6

    PubMed  CAS  Google Scholar 

  70. Perez-Stable E, Halliday R, Gardiner PS, et al. The effects of propanolol on cognitive function and quality of life. Am J Med 2000; 108: 359–65

    PubMed  CAS  Google Scholar 

  71. Diggory P, Cassels-Brown A, Vail A, et al. Avoiding unsuspected respiratory side-effects of topical timolol with cardi-oselective or sympathomimetic agents. Lancet 1995; 345: 1604–6

    PubMed  CAS  Google Scholar 

  72. Webster J, Koch H-F. Aspects of tolerability of centrally acting antihypertensive drugs. J Cardiovasc Pharmacol 1996; 27: S49–54

    PubMed  CAS  Google Scholar 

  73. Cooper KL, McKiernan JM, Kaplan SA. Alpha-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia. Drugs 1999; 57: 9–17

    PubMed  CAS  Google Scholar 

  74. MacKay A, Isles C, Henderson I, et al. Minoxidil in the management of intractable hypertension. QJM 1981; 50: 174–90

    Google Scholar 

  75. Opelz G, Wujciak T, Ritz E. Association of chronic kidney graft failure with recipient blood pressure. Kidney Int 1998; 53: 217–22

    PubMed  CAS  Google Scholar 

  76. Midtvedt K, Hartmann A, Holdaas H, et al. Efficacy of nifedipine or lisinopril in the treatment of hypertension after renal transplantation: a double-blind randomised comparative trial. Clin Transplant 2001; 15: 426–31

    PubMed  CAS  Google Scholar 

  77. Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med 1994; 331: 1286–92

    PubMed  CAS  Google Scholar 

  78. Monton M, Castilla MA, Alvarez Arroyo MV, et al. Effects of angiotensin II on endothelial cell growth: role of AT-1 and AT-2 receptors. J Am Soc Nephrol 1998; 9: 969–74

    PubMed  CAS  Google Scholar 

  79. Yusuf S, Gerstein H, Hoogwerf B, et al. Ramipril and the development of diabetes. JAMA 2001; 286: 1882–5

    PubMed  CAS  Google Scholar 

  80. Stigant CE, Cohen J, Vivera M, et al. ACE inhibitors and angiotensin II antagonists in renal transplantation: an analysis of safety and efficacy. Am J Kidney Dis 2000; 35: 58–63

    PubMed  CAS  Google Scholar 

  81. Schmieder RE, Schlaich MP, Klingbeil AU, et al. Update on reversal of left ventricular hypertrophy in essential hypertension (a meta-analysis of all randomized double-blind studies until December 1996). Nephrol Dial Transplant 1998; 13: 564–9

    PubMed  CAS  Google Scholar 

  82. Klingbeil AU, Muller HJ, Delies C, et al. Regression of left ventricular hypertrophy by ATI receptor blockade in renal transplant recipients. Am J Hypertens 2000; 13: 1295–300

    PubMed  CAS  Google Scholar 

  83. Scolapio JS, Bowen J, Lukens FJ, et al. Influence of tacrolimus and prednisone on serum lipids after liver transplantation. J Parenter Enterai Nutr 2001; 25: 148–51

    CAS  Google Scholar 

  84. Miettinen TA, Pyorala K, Olsson AG, et al. Cholesterollowering therapy in women and elderly patients with myocar-dial infarction or angina pectoris: findings from the Scandinavian Simvastatin Survival Study (4S). Circulation 1997; 96: 4211–8

    PubMed  CAS  Google Scholar 

  85. Lewis SJ, Moye LA, Sacks FM, et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range: results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med 1998; 129: 681–9

    PubMed  CAS  Google Scholar 

  86. Hunt D, Young P, Simes J, et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: results for the LIPID trial. Ann Intern Med 2001; 134: 931–40

    PubMed  CAS  Google Scholar 

  87. Ayanian JZ, Landrum MB, McNeil BJ. Use of cholesterollowering therapy by elderly adults after myocardial infarction. Arch Intern Med 2002; 162: 1013–9

    PubMed  Google Scholar 

  88. Divakar D, Bailey RR, Price M, et al. Effect of diet on post-transplant hyperlipidaemia. NZ Med J 1992 Mar; 105(929): 79–80

    CAS  Google Scholar 

  89. St Peter WL, Clark JL, Levos OM. Drug therapy in haemodialysis patients: special considerations in the elderly. Drugs Aging 1998; 12: 441–59

    PubMed  CAS  Google Scholar 

  90. Ligtenberg G, Hene RJ, Blankestijn PJ, et al. Cardiovascular risk factors in renal transplant patients: cyclosporin A versus tacrolimus. J Am Soc Nephrol 2001; 12: 368–73

    PubMed  CAS  Google Scholar 

  91. Scott JT. Drug-inducted gout. Baillieres Clin Rheumatol 1991; 5(1): 39–60

    PubMed  CAS  Google Scholar 

  92. Mignat C. Clinically significant drug interactions with new immunosuppressive agents. Drug Saf 1997 Apr; 16(4): 267–78

    PubMed  CAS  Google Scholar 

  93. Calmus Y, Conti F, Dousset B, et al. Hepatic allograft rejection: diagnostic and therapeutic aspects. Therapie 1992 Jul–Aug; 47(4): 265–72

    PubMed  CAS  Google Scholar 

  94. Jensen RA, Lal SM, Diaz-Arias A, et al. Does cholestyramine interfere with cyclosporine absorption: a prospective study in renal transplant patients. ASAOI J 1995 Jul–Sep; 41(3): M704–6

    CAS  Google Scholar 

  95. Groggel GC, Cheung AK, Ellis-Benigni K, et al. Treatment of nephrotic hyperlipoproteinemia with gemfibrozil. Kidney Int 1989; 36: 266–71

    PubMed  CAS  Google Scholar 

  96. Evans JR, Forland SC, Cutler RE. The effect of renal function on the pharmacokinetics of gemfibrozil. J Clin Pharmacol 1987; 27: 994–1000

    PubMed  CAS  Google Scholar 

  97. Elisaf MS, Dardamanis MA, Papagalanis ND, et al. Lipid abnormalities in chronic uremic patients: response to treatment with gemfibrozil. Scand J Urol Nephrol 1993; 27: 101–8

    PubMed  CAS  Google Scholar 

  98. Nawrocki JW, Weiss SR, Davidson MH, et al. Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor. Arterioscler Thromb Vasc Biol 1995; 15: 678–82

    PubMed  CAS  Google Scholar 

  99. Kobashigawa JA, Kasiske BL. Hyperlipidemia in solid organ transplantation. Transplantation 1997; 63: 331–8

    PubMed  CAS  Google Scholar 

  100. Castro R, Queiros J, Fonseca I, et al. Therapy of post-renal transplantation hyperlipidaemia: comparative study with simvastatin and fish oil. Nephrol Dial Transplant 1997; 12: 2140–3

    PubMed  CAS  Google Scholar 

  101. Kandus A, Kovac D, Cerne D, et al. Therapy of hyperlipidemia with lovastatin in kidney transplant patients on cyclosporine A immunosuppression: three-year experience. Transplant Proc 1998; 30: 1307–9

    PubMed  CAS  Google Scholar 

  102. Stapleton D, Mehra M, Dumas D, et al. Lipid-lowering therapy and long-term survival in heart transplantation. Am J Cardiol 1997; 80: 802–5

    PubMed  CAS  Google Scholar 

  103. Cosio FG, Pesavento TE, Pelletier RP, et al. Patient survival after renal transplantation (III): the effects of statins. Am J Kidney Dis 2002; 40: 638–43

    PubMed  CAS  Google Scholar 

  104. Wenke K, Meiser B, Thiery J, et al. Simvastatin initiated early after heart transplantation: 8-year prospective experience. Circulation 2003; 107: 93–7

    PubMed  CAS  Google Scholar 

  105. Mehra MR, Uber PA, Vivekananthan K, et al. Comparative beneficial effects of simvastatin and pravastatin on cardiac allograft rejection and survival. J Am Coll Cardiol 2002; 40: 1609–14

    PubMed  CAS  Google Scholar 

  106. Vrtovsnik F, Couette S, Prie D, et al. Lovastatin-induced inhibitions of renal epithelial cell proliferation involves a p21 ras activated, AP-1-dependent pathway. Kidney Int 1997; 52: 1016–27

    PubMed  CAS  Google Scholar 

  107. Bae J, Jarcho JA, Denton MD, et al. Statin specific toxicity in organ transplant recipients: case report and review of the literature. J Nephrol 2002 May–Jun; 15(3): 317–9

    PubMed  Google Scholar 

  108. Cosio FG, Pesavento TE, Osei K, et al. Post-transplant diabetes mellitus: increasing incidence in renal allograft recipients transplanted in recent years. Kidney Int 2001; 59: 732–7

    PubMed  CAS  Google Scholar 

  109. Ericzon B, Groth C, Bismuth H, et al. Glucose metabolism in liver transplant recipients treated with FK 506 or cyclosporin in the European Multicentre Study. Transpl Int 1994; 7: S11–4

    PubMed  Google Scholar 

  110. Midtvedt K, Hartmann A, Hjelmesaeth J, et al. Insulin resistance is a common denominator of post-transplant diabetes mellitus and impaired glucose tolerance in renal transplant recipients. Nephrol Dial Transplant 1998; 13: 427–31

    PubMed  CAS  Google Scholar 

  111. Hjelmesaeth J, Hartmann A, Midtvedt K, et al. Metabolic cardiovascular syndrome after renal transplantation. Nephrol Dial Transplant 2001 May; 16(5): 1047–52

    PubMed  CAS  Google Scholar 

  112. Lebovitz HE. Treating hyperglycemia in type 2 diabetes: new goals and strategies. Cleve Clin J Med 2002; 69: 809–20

    PubMed  Google Scholar 

  113. Moore R, Boucher A, Carter J, et al. Diabetes mellitus in transplantation: 2002 consensus guidelines. Post-Transplant Diabetes Mellitus Advisory Board. Transplant Proc 2003 Jun; 35(4): 1265–70

    PubMed  CAS  Google Scholar 

  114. Hatorp V. Clinical pharmacokinetics and pharmacodynamics of repaglinide. Clin Pharmacokinet 2002; 41: 471–83

    PubMed  CAS  Google Scholar 

  115. Stumvoll M, Nurjhan N, Perriello G, et al. Metabolic effects of metformin in non-insulin dependent diabetes mellitus. N Engl J Med 1995; 333: 550–4

    PubMed  CAS  Google Scholar 

  116. DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 1995; 333: 541–9

    PubMed  CAS  Google Scholar 

  117. Bailey CJ, Turner RC. Drug therapy: metformin. N Engl J Med 1996; 334: 574–9

    PubMed  CAS  Google Scholar 

  118. Lebovitz HE. Insulin resistance: definition and consequences. Exp Clin Endocrinol Diabetes 2001; 109: 135–48

    Google Scholar 

  119. Lebovitz HE, Banerji MA. Insulin resistance and its treatment by thiazolidinediones. Recent Prog Horm Res 2001; 56: 265–94

    PubMed  CAS  Google Scholar 

  120. O’Moore-Sullivan TM, Prins JB. Thiazolidinediones and type 2 diabetes: new drugs for an old disease. Med J Aust 2002; 176: 381–6

    PubMed  Google Scholar 

  121. Lebovitz HE, Kreider M, Freed MI. Evaluation of liver function in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction. Diabetes Care 2002; 25: 815–23

    PubMed  CAS  Google Scholar 

  122. Lebovitz HE. Oral therapies for diabetic hyperglycemia. Endocrinol Metab Clin North Am 2001; 30: 909–33

    PubMed  CAS  Google Scholar 

  123. Helderman JH, Goral S. Gastrointestinal complications of transplant immunosuppression. J Am Soc Nephrol 2002; 13: 277–87

    PubMed  Google Scholar 

  124. Stelzner M, Vlahakos DV, Milford EL, et al. Colonic perforations after renal transplantation. J Am Coll Surg 1997; 184: 63–9

    PubMed  CAS  Google Scholar 

  125. Warshaw AL, Welch JP, Ottinger LW. Acute perforation of the colon associated with chronic corticosteroid therapy. Am J Surg 1976; 131: 442–6

    PubMed  CAS  Google Scholar 

  126. Merrell SW, Ames SA, Nelson EW, et al. Major abdominal complications following cardiac transplantation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program. Arch Surg 1989; 124: 889–94

    PubMed  CAS  Google Scholar 

  127. Tranaeus A, Heimburger O, Granqvist S. Diverticular disease of the colon: a risk factor for peritonitis in continuous peritoneal dialysis. Nephrol Dial Transplant 1990; 5: 141–7

    PubMed  CAS  Google Scholar 

  128. McCune TR, Nylander WA, Van Buren DH, et al. Colonic screening prior to renal transplantation and its impact on posttransplant colonic complications. Clin Transplant 1992; 6: 91–6

    PubMed  CAS  Google Scholar 

  129. Torregrosa JV. Immunosuppression and bone loss after transplantation. Transplant Proc 2001; 33: 3665–7

    PubMed  CAS  Google Scholar 

  130. Haagsma EB, Thijn CJ, Post JG, et al. Bone disease after orthotopic liver transplantation. J Hepatol 1998; 6: 94–100

    Google Scholar 

  131. Riemens SC, Oostdijk A, van Doormaal JJ, et al. Bone loss after liver transplantation is not prevented by cyclical etidronate, calcium and alphacalcidol. Osteoporos Int 1996; 6: 213–8

    PubMed  CAS  Google Scholar 

  132. Hommann M, Abendroth K, Lehmann G, et al. Effect of transplantation on bone: osteoporosis after liver and multivisceral transplantation. Transplant Proc 2002; 34: 2296–8

    PubMed  CAS  Google Scholar 

  133. De Sevaux RG, Hoitsma AJ, Van Hoof HJ, et al. Abnormal vitamin D metabolism and loss of bone mass after renal transplantation. Nephron 2003; 93: C21–8

    PubMed  Google Scholar 

  134. Hawkins FG, Leon M, Lopez MB, et al. Bone loss and turnover in patients with liver transplantation. Hepatogastroenterology 1994; 41: 158–61

    PubMed  CAS  Google Scholar 

  135. Meys E, Fontanges E, Fourcade N, et al. Bone loss after orthotopic liver transplantation. Am J Med 1994; 97: 445–50

    PubMed  CAS  Google Scholar 

  136. Monegal A, Navasa M, Guañabens N, et al. Osteoporosis and bone mineral metabolism disorders in cirrhotic patients referred for orthotopic liver transplantation. Calcif Tissue Int 1997; 60: 148–54

    PubMed  CAS  Google Scholar 

  137. Pisani B, Mullen GM. Prevention of osteoporosis in cardiac transplant recipients. Curr Opin Cardiol 2002; 17: 160–4

    PubMed  Google Scholar 

  138. Saag K, Emkey R, Schnitzer T, et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. N Engl J Med 1998; 339: 292–9

    PubMed  CAS  Google Scholar 

  139. Shane E, Rodino M, McMahon D, et al. Prevention of bone loss after heart transplantation with antiresorptive therapy: a pilot study. J Heart Lung Transplant 1998; 17: 1089–96

    PubMed  CAS  Google Scholar 

  140. Krieg MA, Seydoux C, Sandini L, et al. Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study. Osteoporos Int 2001; 12: 112–6

    PubMed  CAS  Google Scholar 

  141. Trzepacz PT, Maue FR, Coffman G, et al. Neuropsychiatric assessment of liver transplantation candidates: delirium and other psychiatric disorders. Int J Psychiatry Med 1986; 16: 101–11

    PubMed  Google Scholar 

  142. Dew MA, Roth LH, Schulberg HC, et al. Prevalence and predictors of depression and anxiety-related disorders during the year after heart transplantation. Gen Hosp Psychiatry 1996; 18: 48–61S

    Google Scholar 

  143. Lake KD. Management of drug interactions with cyclosporine. Pharmacotherapy 1991; 11(5): 110–118S

    Google Scholar 

  144. Vella JP, Sayegh M. Interactions between cyclosporine and newer antidepressant medications. Am J Kidney Dis 1998; 31: 320–3

    PubMed  CAS  Google Scholar 

  145. Helms-Smith KM, Curtis SL, Hatten RC. Apparent interaction between nefazodone and cyclosporine [letter]. Ann Intern Med 1996; 125: 424

    PubMed  CAS  Google Scholar 

  146. Wright DH, Lake KD, Bruhn PS, et al. Nefazodone and cyclosporine drug-drug interaction. J Heart Lung Transplant 1999; 18: 913–5

    PubMed  CAS  Google Scholar 

  147. Horton RC, Bonser RS. Interaction between cyclosporin and fluoxetine. BMJ 1995; 311: 422

    PubMed  CAS  Google Scholar 

  148. Strouse TB, Fairbanks LA, Skotzko CE, et al. Fluoxetine and cyclosporine in organ transplantation. Psychosomatics 1996; 37: 23–30

    PubMed  CAS  Google Scholar 

  149. Markowitz JS, Gill HE, Hunt NM, et al. Lack of antidepressant-cyclosporine pharmacokinetic interactions. J Clin Psycho-pharmacol 1998; 18: 91–3

    CAS  Google Scholar 

  150. Willetts J, Lippa A, Beer B. Clinical development of citalopram. J Clin Psychopharmacol 1999; 19: 36S–46S

    PubMed  CAS  Google Scholar 

  151. Liston HL, Markowitz JS, Hunt N, et al. Lack of citalopram effect on the pharmacokinetics of cyclosporine. Psychosomatics 2001 Jul–Aug; 42(4): 370–2

    PubMed  CAS  Google Scholar 

  152. Gravenstein S, Davidson HE. Current strategies for management of influenza in the elderly population. Clin Infect Dis 2002; 35: 729–37

    PubMed  Google Scholar 

  153. Treanor J, Falsey A. Respiratory viral infections in the elderly. Antiviral Res 1999; 44: 79–102

    PubMed  CAS  Google Scholar 

  154. Kasiske B. Long-term posttransplantation management and complications. In: Danovitch GM, editor. Handbook of kidney transplantation. 3rd ed. Philadelphia (PA): Lippincott Williams & Wilkins, 2001: 182–220

    Google Scholar 

  155. Butler JC, Schuchat A. Epidemiology of pneumococcal infections in the elderly. Drugs Aging 1999; 15: 11–9

    PubMed  Google Scholar 

  156. Penn I, Hammond W, Brettschneider L, et al. Malignant lymphomas in transplantation patients. Transplant Proc 1969; 1: 106–12

    PubMed  CAS  Google Scholar 

  157. Harden PN, Reece SM, Fryer AA, et al. Skin cancer surveillance in renal transplant recipients: questionnaire survey of current UK practice. BMJ 2001; 323: 600–1

    PubMed  CAS  Google Scholar 

  158. London NJ, Farmery SM, Will EJ, et al. Risk of neoplasia in renal transplant patients. Lancet 1995; 72: 403–6

    Google Scholar 

  159. Penn I. The changing patterns of post-transplant malignancies. Transplant Proc 1991; 23: 1101–3

    PubMed  CAS  Google Scholar 

  160. Euvrard S, Kanitakis J, Pouteil-Noble C. Skin cancers in organ transplant recipients. Curr Opin Organ Transplant 1998; 3: 96–104

    Google Scholar 

  161. Barrett WL, First MR, Aron BS, et al. Clinical course of malignancies in renal transplant patients. Cancer 1993; 72: 2186–9

    PubMed  CAS  Google Scholar 

  162. Opelz G, Henderson R. Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients. Lancet 1993; 342: 1514–6

    PubMed  CAS  Google Scholar 

  163. Penn I. De novo cancers in organ allograft recipients. Curr Opin Organ Transplant 1998; 3: 188–96

    Google Scholar 

  164. Winkelhorst JT, Brokelman WJ, Tiggeler RG, et al. Incidence and clinical course of de-novo malignancies in renal allograft recipients. Eur J Surg Oncol 2001; 27: 409–13

    PubMed  CAS  Google Scholar 

  165. Danpanich E, Kasiske BL. Risk factors for cancer in renal transplant recipients. Transplantation 1999; 68: 1859–64

    PubMed  CAS  Google Scholar 

  166. Haagsma EB, Hagens VE, Schaapveld M, et al. Increased cancer risk after liver transplantation: a population-based study. J Hepatol 2001 Jan; 34(1): 84–91

    PubMed  CAS  Google Scholar 

  167. Fabia R, Levy MF, Testa G, et al. Colon carcinoma in patients undergoing liver transplantation. Am J Surg 1998; 176: 265–9

    PubMed  CAS  Google Scholar 

  168. Knechtle SJ, D’Alessandro AM, Harms BA, et al. Relationships between sclerosing cholangitis, inflammatory bowel disease, and cancer in patients undergoing liver transplantation. Surgery 1995; 118: 615–9

    PubMed  CAS  Google Scholar 

  169. Orth SR, Ritz E, Schrier RW. The renal risks of smoking. Kidney Int 1997; 51: 1669–77

    PubMed  CAS  Google Scholar 

  170. Kalker AJ, Pirsch JD, Heisey D, et al. Foot problems in the diabetic transplant recipient. Clin Transplant 1996; 10: 503–10

    PubMed  CAS  Google Scholar 

  171. Weitzner MA, Haley WE, Chen H. The family caregiver of the older cancer patient. Hematol Oncol Clin North Am 2000; 14: 269–81

    PubMed  CAS  Google Scholar 

  172. Balducci L, Extermann M. Management of the frail cancer patient. Crit Rev Oncol Hematol 2000; 33: 143–8

    PubMed  CAS  Google Scholar 

  173. Corcoran MB. Polypharmacy in the older patient. In: Balducci L, Lyman GH, Ershler WB, editors. Comprehensive geriatric oncology. London: Harwood Academic Publishers, 1997: 525–32

    Google Scholar 

  174. Wenger NK. Lipid metabolism, physical activity, and postmenopausal hormone therapy. Am J Kidney Dis 1998; 32: S80–8

    PubMed  CAS  Google Scholar 

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Bernardo, J.F., McCauley, J. Drug Therapy in Transplant Recipients. Drugs Aging 21, 323–348 (2004). https://doi.org/10.2165/00002512-200421050-00004

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