Jean Shallcross, BSc (Hons), MSc, DPSN, RN. Nurse Clinician, Renal Transplant Unit, Royal Liverpool University Hospital.
An increasing number of new immunosuppressive agents have emerged in the past decade. This wider range of therapeutic options presents a major challenge in deciding the ideal immunosuppressive regimen for each individual patient.
Nurses have an important role in helping tailor individual immunosuppressive regimens to maximise patient and kidney graft survival and to aid concordance with treatment, a key issue in managing transplant patients. Within the Mersey Regional Health Authority, recognition of the nurse’s vital role in managing transplant patients has seen the creation of the position of nurse clinician.
Kidney transplantation is indicated for chronic renal failure, which can be caused by a wide range of conditions in children and adults. The only alternatives in end-stage renal failure are haemodialysis or peritoneal dialysis. Kidney transplantation offers the benefits of freedom from the daily dialysis routine, removal of dietary and fluid restrictions, and an improved sense of well-being.
Over the past 40 years, immunosuppressive drug regimens have developed greatly and transformed solid organ transplantation into a routine clinical procedure, with impressive short-term results being obtained in kidney transplantation. However, in the absence of immunosuppression, transplanted organs invariably undergo progressive immune-mediated injury.
Immunosuppressants were first introduced in the 1950s in the form of steroids and the antiproliferative agent, azathioprine. During the 1960s, the first polyclonal antibodies were introduced, but it was not until clinical trials of cyclosporin in the late 1970s that major progress was made in the field of transplantation (Lee, 1998; Webb, 1998). Today, the greatly expanded choice of immunosuppressive agents allows greater flexibility in tailoring therapy to the needs of individual transplant recipients.
One-year graft survival for kidney transplants now averages over 90%. Even at five years post-transplant, between 70 and 80% of grafts are reported to survive. However, after this period, the rate of graft loss starts to accelerate so that by 10 years post-transplant only about 40% of all kidney grafts continue to function successfully. Causes of this long-term graft attrition are multifactorial. (Denton, et al, 1999; Kreis and Ponticelli, 2001).
Causes of chronic graft dysfunction
Chronic and acute rejection are different entities and this is reflected by the differences in their histologic picture as well as in their predisposing factors. Histocompatibility and/or insufficient immunosuppression are well-known risk factors for acute rejection. However, as more potent immunosuppression has been developed, very few renal transplants are now lost from acute rejection.
In chronic graft failure, a variety of predisposing factors seem to contribute (Box 1). It is important to note that not all the factors listed in Box 1 are immunological responses to a transplant. Chronic transplant nephropathy accounts for 30% of graft loss and is one of the commonest causes of the need for dialysis (Moore, 2000).
Box 2 lists drugs used today in renal transplantation.
One key issue in transplantation is how much immunosuppressive therapy should be given. Too little risks acute rejection, but too much may cripple the immune system. Other than the drug-specific effects, immunosuppression increases the risk of infections, including bacterial disease, viruses (particularly cytomegalovirus and herpes zoster), and fungal conditions, such as candida. There is also a risk of post-transplant lymphoproliferative disease. This disorder may respond to a reduction in the dose of immunosuppression, but can be fatal (Amlot, 2000).
In the long term, immunosuppression is associated with further risks, including:
- Malignancy, which is common among transplant patients
- Ischaemic heart disease (related to drug-associated hypertension, nephrotoxicity and lipid abnormalities)
- Osteoporosis, especially in relation to steroids (Paul, 1999; Ball et al, 2000).
A related issue is whether a patient should be given just one basic type of immunosuppression or be treated using a combined approach. Some transplant centres are championing monotherapy regimens in which well-matched patients are treated with either cyclosporin or tacrolimus therapy in the absence of any other form of immunosuppression. However, many centres supplement tacrolimus or cyclosporin with steroid and/or antiproliferative drugs in dual- or triple-therapy regimens.
Although dual- and triple-therapy regimens are said to reduce the risk of rejection (Lee, 1998) they also increase the side-effect burden, the potential for drug interactions, and complicate the medication that the patient has to take. Concordance is more difficult when a patient has to take many tablets at different times of the day (Keown, 2001).
While graft survival at one year has increased over the past decade, long-term graft failure remains a major problem (Moore, 2000).
Non-concordance is known to be an important factor in graft failure (Fernando, 1997) and represents a significant health risk for patients (Box 3). Non-concordance with immunosuppressive medications has been reported to be the third leading cause of such loss, after rejection and systemic infection (Greenstein and Siegal, 1998).
All immunosuppressive agents have side-effects, and this can be a key factor affecting patient concordance. Since patients must continue taking immunosuppressive treatments for the life of their graft, it is essential to take into account the side-effect profiles of different agents and their potential impact on patient concordance. For example, altered body image can cause renal transplant recipients great anxiety and stress, while cosmetic and general side-effects can affect concordance with the immunosuppressive regimen (Hasselder, 1999).
From the health professional’s point of view, the care pathway for a patient with kidney failure alternates between dialysis and transplantation. For the patient, transplantation does not simply represent a solution, but involves a transition to a completely new set of problems (Berry, 1998). All the above factors, combined with personal and psychological issues, can have a profound effect on concordance and need to be addressed by the transplant unit (Valentine, 2000). The patient’s perspective is of great importance.
Managing a successful transplant involves communication, education, as well as understanding by the patient of the treatment and its side-effects. Monitoring clinical outcome requires regular follow-up of all patients by the transplant team. The focus of patient management is on long-term survival of the kidney graft and the long-term physical and mental health of the transplant recipient. The transplant nurse has a particular role in this area (Lipkin, 1999). Concordance management is a multidisciplinary task but the role of the nurse is critical (De Geest, 1998).
The transplant nurse practitioner
The response of the individual patient to life with a transplant vary greatly: age, gender, employment status, stability, security and personality will all have an impact.
Education and support are probably the most important ways in which nurses can influence patients. Throughout the entire process of transplantation, from first entering the waiting list, through the operative period itself, to the follow-up care stage, there is a need for extensive nursing input (Mackenzie, 2001).
The best approach is to build a relationship with the transplant recipient throughout the process and develop a caring, supportive environment in which patients feel able to discuss problems (Fernando, 1997; Hasselder, 1999). High-quality education is also needed. This should start before the transplant so that patients are aware of the potential side-effects of the drugs they will be taking (Trevitt et al, 2000). Some patients may feel intimidated by doctors, while others leave the clinic unable to remember all the information they have been given. To help overcome these problems many hospitals employ nurse practitioners.
The nurse clinician
Nurse clinicians have been employed at the Royal Liverpool University Hospital Renal Transplant Unit since 1997. The Mersey Regional Health Authority developed the role in 1995 in response to a number of policy changes affecting the NHS, including the development of primary care services, the rationalisation of acute services, the reduction in junior doctors’ hours, EU regulations on medical education and training, and the UKCC’s Scope of Professional Practice for nurses (1992).
The nurse clinician, educated to master’s degree level in clinical nursing, complements the doctor’s role in the delivery of health care by developing skills such as history-taking, clinical examination, pharmacology and therapeutic communication, together with a knowledge of anatomy and physiology.
A nurse clinician was originally employed by the transplant unit to cover a shortfall in junior doctors. The role has developed over the past four years and the nurse clinician is now involved in the provision of both outpatient and inpatient care, facilitating continuity from pre-transplant assessment through to transplantation and discharge. This provision bridges the entire transplant process.
The nurse clinician role not only complements the doctor’s role, but also supplements the work of the nurse-led clinic, established in the transplant ward in 1994 (Box 4). The complementary roles of nurse clinician and the nurse-led clinic provide a unique opportunity to combine a holistic approach to the care of renal transplant patients (Holley and McGuirl, 2000). There is evidence that patients find high levels of satisfaction from nurse consultations (Murray, 1997) and are accepting of alternative care delivery systems (Fitzmaurice et al, 2000).
Key roles of nurses in renal transplantation
Non-concordance with immunosuppressive medications is common among renal transplant patients and is a significant contributor to graft loss. Nurses can play a key role in the multidisciplinary team in the prevention of problems, providing early detection and prompt management. The friendliness of a particular team may be an important factor. Patients may feel the transplant does not eliminate health-related stress, so they need to be able to approach non-physician members and discuss particular problems in regard to how they handle the demands of their therapy.
It may, for example, be necessary to alter the patient’s drug regimen in order to avoid side-effects of immunosuppression and also to make the regimen as simple as possible. Newer agents are now available which appear to have side-effect profiles that impact less on patients’ quality of life, and this factor will, it is hoped, produce better long-term graft survival and improved overall quality of life (Macdonald, 2000). The most recent immunosuppressant, sirolimus, offers a baseline immunosuppressive regimen that minimises the cosmetic side-effects and nephrotoxicity associated with cyclosporin and has the added advantage of once-a-day dosing. This may promise easier patient tolerance and greater concordance.
The role of the nurse in transplant patient care has enhanced the transplant service for both the patient and the multidisciplinary team (Valentine and Russell, 1998; Reece, 1999). One goal of treating transplant patients is to ensure that their quality of life is as high as possible, and monitoring the side-effects of immunosuppression regimens is a way to help achieve this. Nurses have more interaction with patients than any other health professionals, giving them an advantage when monitoring for side-effects, such as cardiovascular risk factors, which may not be immediately apparent to the patient as more superficial problems.
It is important to support nurses in their educational role so that, as new drugs become more widely used, nurses have the relevant knowledge to enable them to work in partnership with patients.
New immunosuppressant drugs offer the potential to minimise post-transplantation morbidity by reducing cardiovascular risk, toxicity and side-effects and improving quality of life. Transplantation gives patients the offer of a new life and the nurse, through patient education and risk profiling, can play a major role in helping the patient enjoy a better quality of life (Mackenzie, 2001).
Allen, R., Chapman, J. (1994) A Manual of Renal Transplantation. London: Edward Arnold.
Amlot, P. (2000)Post-transplant lymphoproliferative disease. In: Myths and Reality. Transplantation Developments and Dilemmas. Addressing the long-term complications of renal transplantation (Royal College of Physicians, London. April 2, 2000). Basel, Switzerland: Novartis Pharma.
Anderson, F. (1998)Best practice in oral corticosteroid prescribing. Hospital Update January (suppl); 2-8.
Ball, E.A., Trevitt, R., Whittaker, C., Fitzgerald, L. (2000)Cardiovascular disease (CVD) risk factor profiling in renal transplant recipients in nurse-led clinics. European Dialysis and Transplant Nurses’ Association; XXVI: 53.
Berry, J. (1998)‘More to life than medicine’: the patient’s view of the transplant process. Summary of Proceedings: Immunology and transplant (Royal London Hospital, October 26, 1998) Tunbridge Wells: Williams Blake Reay Ltd.
Dantal, J., Hourmant, M., Cantarovich, D. et al. (1998)Effects of long-term immunosuppression in kidney graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens. Lancet 351: 623-628.
De Geest, S. (1998)Non-compliance: a threat to graft survival. Summary of Proceedings: Immunology and transplant (Shrigley Hall, November 24, 1998). Tunbridge Wells: Williams Blake Reay Ltd.
Denton, M., Magee, C., Sayegh, M. (1999)Immunosuppressive strategies in transplantation. Lancet 353: 1083-1091.
Fellstrom, B. (1999)The effects of lipids on graft outcome. Transplantation Proceedings 31: 7A, 145-155.
Fernando, O. (1997)Compliance keeps kidneys. Medical Interface November, 15-18.
Fitzmaurice, D.A., Hobbs, F.D., Murray, E.T. (2000)Oral anticoagulation management in primary care with the use of computerised decision support and near patient testing: a randomised controlled trial. Evidence Based Nursing 4: 2, 52.
Fulton, B., Markham, A. (1996)Mycophenolate mofetil. Drugs 51: 2, 278-298.
Greenstein, S., Siegal, B. (1998)Compliance and non-compliance in patients with a functioning renal transplant: a multicenter study. Transplantation 66: 12, 1718-1726.
Groth, C.G., Backman, L., Morales, J-M. et al. (1999)sirolimus (rapamycin)-based therapy in human renal transplantation. Transplantation 67: 7, 1036-1042.
Hardstaff, R., Green, D., Talbot, D. (2001)Non-compliance in renal transplantation: determining the extent of the problem using electronic surveillance. Proceedings of the British Transplant Society 4th Annual Congress. Oxford: British Transplant Society.
Hasselder, A. (1999)Renal transplant: long-term effects of immunosuppression. Professional Nurse 14: 11, 771-777.
Holley, J.L., McGuirl, K. (2000)Advanced practice nurses in ESRD: varied roles and cost analysis. Nephrology News and Issues February, 18 31.
Kahan, B.D., Julian, B.D., Pescovitz, M.D. et al. (1999)Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Transplantation 68: 10, 1526-1532.
Keown, P. (2001)Improving quality of life: the new target for transplantation. Transplantation 72: 12 (suppl), S67-S74.
Kreis, H.A., Ponticelli, C. (2001)Causes of late renal allograft loss: chronic allograft dysfunction, death, and other factors. Transplantation 71: 11, SS5-SS9.
Lee, M. (1998)Anti-rejection drugs past and present. Summary of Proceedings: Immunology and transplant (Shrigley Hall, November 24, 1998). Tunbridge Wells: Williams Blake Reay Ltd.
Lipkin, G. (1999)The long-term complications of immunosuppression and transplantation. Care in Transplantation 1: 3-4.
Macdonald, A. (2000)Improving tolerability of immunosuppressive regimens. Transplantation 72: 12 (suppl), S105-S112.
Mackenzie, K.M. (2001)Philosophical and ethical issues in human organ transplantation. British Journal of Nursing 10: 7, 433-437.
Mayer, A. D. (1999)Tacrolimus as baseline immunosuppression in kidney transplantation. New Horizons in Kidney Transplantation 2: 1, 10.
Mayer, A.D., Dmitrewski, J., Squifflet, J.R. et al. (1997)Multicenter randomised trial comparing tacrolimus and cyclosporine in the prevention of renal allograft rejection. A report of the European Tacrolimus Multicenter Renal Study Group. Transplantation 64: 3, 436-443.
Moore, R. (2000)New immunosuppressive agents; what part can they play? In: Myths and Reality. Transplantation Developments and Dilemmas. Addressing the long-term complications of renal transplantation (Royal College of Physicians, London. April 2, 2000). Basel, Switzerland: Novartis Pharma.
Murray, S. (1997)A nurse-led clinic for patients with peripheral vascular disease. British Journal of Nursing 6:13, 726-736.
Ojo, A.O., Meier-Kriesche, H.U., Hanson, J.A. et al. (2000)Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation 69: 11, 2405-2409.
Paul, L.C. (1999)The future of new immunosuppressive drugs. New Horizons in Kidney Transplantation 2: 1, 8.
Pirsch, J.D., Miller, J., Deierhoi, M.H. et al. (1997)A comparison of tacrolimus and cyclosporine for immunosuppression after cadaveric renal transplantation. Transplantation 63: 7, 977-993.
Reece, S. (1999)Cosmetic side- effects care in transplantation. Transplantation 1: 5.
Sollinger, H.W. (1995)Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Renal Transplant Mycophenolate Mofetil Study Group. Transplantation 60: 3, 225-232.
Spickett, G.P. (1992)Immunosuppression and the drug therapy of allergies, connective tissue disorders, and primary immunodeficiencies. In: Grahame-Smith, D.G., Aronson, J.K. (eds). Oxford Textbook of Clinical Pharmacology and Drug Therapy (2nd edn). Oxford: Oxford University Press.
Trevitt, R., Whittaker, C., Ball, E.A. (2000)Evaluation of potential transplant recipients and living donors. European Dialysis and Transplant Nurses’ Association/European Renal Care Association XXVI: 1, 26-28.
UKCC. (1992)The Scope of Professional Practice. London: UKCC.
Valentine, A.M., Russell, S.A. (1998)A role for the nurse practitioner in renal transplantation. Nephrology Nurses Forum 2: 10-12.
Valentine, A. (2000)Is it surprising they omit their tablets? European Dialysis and Transplant Nurses’ Association/European Renal Care Association Journal XXVI: 2, 36-38.
Vanrentergham, Y. (1998)Tacrolimus in kidney transplantation. Transplantation Proceedings 30: 2171-2173.
Watson, C.J.E. (2001)Sirolimus (Rapamycin) in clinical transplantation. Transplantation Reviews 15: 4, 165-177.
Webb, M. (1998)Disarming the immune response: anti - rejection drugs. Summary of Proceedings: Immunology and transplant (Royal London Hospital, October 26, 1998) Tunbridge Wells: Williams Blake Reay Ltd.