New transplant technologies and immunosuppressant agents have caused an increase in demand for organ transplantation as potential treatments for end-stage heart, lung, liver, kidney, pancreas, and small bowel diseases.1,2 Transplantation is now a common and standard procedure performed in Australia. However, despite the success of various past organ transplants, rejection and various complications remain pertinent issues. Relative organ shortages in Australia also demand that our organs are distributed and used efficiently and effectively.1 This article therefore provides a brief overview of some common complications post-transplant and appropriate management strategies.
The 20th century has seen rapid developments in the field of organ transplantation. Following the first successful living-related kidney transplant by Dr Joseph E Murray in Boston in the 1950s, kidney, liver, cornea, pancreas, heart, lung and bone marrow transplants have now become standard procedures.3 Organ transplants have offered breakthroughs in patients with various end-stage diseases and offered new hopes for survival and restoration of health.2 Furthermore, improved surgical techniques and new immunosuppressive drugs have led to transplantation being performed in increasing numbers of patients with excellent survival results.2Successful organ transplantation has hinged on recognition of the mechanisms involved in graft rejection and adequate immunosuppression. Although the highest risk of rejection occurs in the first three months, indefinite immunosuppressant therapy is required in virtually all transplant patients irregardless of the HLA compatibility of the donor and recipient.3,4 Corticosteroids, cyclosporine, tacrolimus, and antilymphocyte and antithymocyte globulins are frequently employed agents used in variable combinations. Potent immunosuppressive agents have dramatically reduced the incidence of rejection but unfortunately have brought new complications of infections, steroid side effects (including Cushingoid features and osteoporosis) bone marrow suppression and occasionally malignancies.4, 5 In fact, immunosuppressant drugs can contribute to the pathogenesis of the major causes of death in the late post-transplant period, namely cardiovascular disease, cancer and infection.6 It is thus of paramount important that immunosuppressant therapy is carefully tailored and where relevant minimised to the appropriate maintenance levels.4, 6 Non-compliance with immunosuppressant medications is thought to be a common phenomenon in transplant recipients, posing serious risks of graft failure.6 The exact rates of non-compliance are unknown and it is likely that figures underestimate the true value as patients would be reluctant to disclose their non-compliance due to fears it may jeopardise their transplant eligibility.6 Causes of non-compliance may be varied from false beliefs regarding the effects and mechanisms or medications, to innocently forgetting medications due to highly complicated drug regimes.6 Ongoing patient education, support and use of medication reminder aids can thus assist in overcoming this problem. Infection post transplantation is another major cause of morbidity and mortality.1 Prevention and management of infections is challenging due to the various potential sources of infections.7 Certain viruses may be transmitted during organ transplantation (such as cytomegalovirus, herpes simplex virus, Epstein-Barr virus, human immunodeficiency virus, hepatitis A virus, hepatitis B virus, hepatitis D virus and human T-cell lymphotropic virus type 1) therefore strict screening protocol are employed for potential organ donors.1 Post-transplant patients are also exposed to a range of community and nosocomial pathogens and their immunosuppressant therapy may hinder the body’s inflammatory response increasing their susceptibility to infection and/or delaying recognition of invasive infections.1,7 Furthermore, emerging drug resistance, drug-drug interactions, and medication toxicities pose additional challenges.8 It is thus recommended that organ recipients undergo routine antimicrobial prophylaxis against Pneumocystis carinii and cytomegalovirus, receive regular vaccinations against influenza and Pneumococcus, and follow close surveillance and treatment of any opportunistic infections.6,8 Medical practitioners may refer to hospital guidelines for the recommended treatment and prophylaxis regimes for specific types of organ transplants. Post-transplant malignancy rates are estimated to be approximately 4-5 times that of the aged matched general population, thus effective screening and surveillance programs are essential to the management of a transplant recipient.6,9,10 Immunosuppressant therapy and carcinogenic viruses (such as Epstein Barr virus causing lymphoproliferative disorders) are thought to be contributing factors. The highest-risk cancers in transplant recipients include skin cancer, Kaposi’s sarcoma, anogenital cancers, lymphomas, hepatocellular cancers in liver transplant recipients, renal cell carcinomas and cervical carcinoma.9 Routine skin self-examination, annual formal dermatologic evaluations and general population screening strategies for breast, colon, cervical, and prostate cancer should be integrated into post-transplant care.9 In addition, patients should be counseled to avoid ultraviolet exposure and to use appropriate sun protective agents.4, 6Cardiovascular disease is a further complication following transplantation, particularly pertinent to patients with end-stage renal disease.6,9 Aggressive treatment (including pharmacological and lifestyle treatment) of hyperlipidaemia and hypertension is therefore recommended in transplant management. Ideally cardiovascular status and risks should be evaluated and addressed prior to transplant but such issues have the potential to be overlooked due to strong focuses on post-transplantation immunosuppression.9 Standard heart foundation recommendations for cardiovascular disease prevention and lipid guidelines should be employed. A final potential complication post-transplant is the recurrence of specific primary diseases. Routine measurements of end organ function (such as renal or liver function tests) may be helpful in identifying early organ failure or rejection. Depending on the disease, more specific investigations may also be required. It is essential that the above common complication issues are addressed so that organ transplantation can produce improved survival and quality of life. Organ transplantation has the potential to cure several end-stage diseases so it is important that efforts continue to optimise management strategies. References:
- Kerridge I, Saul P, Batey R. The clinical and ethical implications of hepatitis C for organ transplantation in Australia. MJA 1996; 165: 282-5.
- Burra P, De Bona M, Germani G, Canova D, Masier A, Tomat S, Senzolo M. The concept of quality of life in organ transplantation. Transplantation Proceedings 2007; 39 (7): 2285-7.
- Burkitt, Quick. Essential Surgery, 3rd Edition, Churchill Livingstone, 2002; pp. 37-42.
- Kumar, Clark. Clinical Medicine, 5th Edition, Saunders, 2002; pp. 656-658, 873.
- Fishman J. Infection in solid-organ transplant recipients. NEJM 2007; 357 (25): 2601-14.
- Sahadevan, Kasiske. Long-Term Posttransplant Management and Complications (Chapter 9) in Danovitch G. Handbook of Kidney Transplantation, 4th Ed, Lippincott Williams and Wilkins, 2004.
- Fishman J, Rubin R. Infection in organ-transplant recipients. NEJM 1998; 338 (24): 1741-51.
- Chiu, Loretta M, Domagala, Beata M, Park, Jeong M. Management of opportunistic infections in solid-organ transplantation. Progress in Transplantation. 2004; 14: 114-29.
- Danovitch G. Clinical Practice Guidelines for Management of the Transplant Recipient, Medscape, Conference Coverage, 2000. Available [online] at URL http://www.medscape.com/viewarticle/420535
- Dantal J, Soulillou J-P, Immunosuppressive drugs and the risk of cancer after organ transplantation. NEJM 2005; 352 (13): 1371-3.