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1. Cardiovascular Disease

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References

Guideline recommendations

  1. We recommend that all candidates for kidney transplant are screened for cardiovascular risk factors (1B). Indicators of high risk include (1B):
    • Older age.
    • Diabetes mellitus.
    • Abnormal echocardiogram (ECG).
    • Previous ischaemic heart disease or congestive heart failure.
    • Increased duration of dialysis.
    • Smoker.
  2. We suggest that kidney transplant candidates with a low clinical risk of cardiovascular disease do not require stress testing for coronary artery disease (2B).
  3. We suggest that kidney transplant candidates with a moderate or high clinical risk of cardiovascular disease undergo cardiac stress testing prior to transplantation (2B). The following should be noted in relation to cardiac stress testing in dialysis patients:
    • Exercise ECG has a poor predictive value in patients on dialysis (2B).
    • The use of a cardiac stress test such as dipyridamole thallium testing or stress echocardiography is predictive of significant coronary artery disease and major cardiac events in patients with higher clinical risk. Where possible we recommend that this testing should be performed without concurrent β-blocker therapy (1B).
    • As the prognostic accuracy of cardiac stress testing in dialysis patients is of limited duration, it is suggested that testing be repeated in high risk patients. The interval at which testing should take place has not been well defined; however, the predictive value of a positive test diminishes after 24 months (2C).
  4. We recommend that coronary angiography be considered for kidney transplant candidates with abnormalities on screening procedures (1B).
  5. We suggest that the benefit of revascularization prior to transplantation be reviewed on an individual basis (2C).

Ungraded suggestions for clinical care

  • Reduced left ventricular systolic function is predictive of reduced survival for patients with end-stage renal failure. A reduced fractional shortening, or an increased end-systolic diameter, are the best validated echocardiographic indices for predicting this (ungraded).
  • In general, there is no strong evidence to suggest that revascularization of asymptomatic coronary artery stenoses in patients with renal failure is associated with beneficial outcomes after renal transplantation (ungraded).
  • Dialysis patients with carotid plaque are likely to be at higher risk of mortality than those without carotid plaque; however, there is no evidence to suggest which patients should be screened for carotid plaques (ungraded).
  • Kidney transplant candidates with diabetes mellitus and atrial fibrillation should be identified as having a higher risk of post-transplantation cerebrovascular events. (ungraded)

Background

Cardiovascular disease is one of the most common causes of morbidity, and the most frequent cause of mortality in patients on dialysis as well as those with kidney transplants. Furthermore, the National Vascular Disease Prevention Alliance ‘Guidelines for the Management of Absolute Cardiovascular Disease Risk (2012)’[1] (approved by the NHMRC) identifies identify those aged 45 years and older with epidermal growth factor receptor (eGFR) <45 mL/min per 1.73 m2 as being of high risk (defined as >15% risk of cardiovascular disease within the next 5 years). Therefore, assessing patients for the presence of cardiac disease is an important aspect of assessment for renal transplantation.

These guidelines do not determine which patients are, and therefore by inference, which patients are not, suitable for transplantation. With the possible exception of highly obese individuals (refer to ‘Obesity’ subtopic). There is no good evidence that any group of patients referred for renal transplantation has a worse long-term prognosis by having a transplant, than by staying on dialysis.[2-9] As mortality and morbidity from cardiovascular disease is higher than the general population, most units routinely screen for cardiovascular disease in those patients at highest risk for cardiovascular system events.

In this guideline, we review the current data regarding cardiovascular risk factors and cardiac screening and the relationship of screening to cardiovascular events and mortality. Additionally we review the evidence for revascularization prior to transplantation in patients with coronary artery disease.

The assessment of patients to receive a renal transplant on the basis of their cardiovascular disease does not lend itself to randomized-controlled trials. Where possible, Cohort studies that look at the impact of cardiovascular disease on the outcomes of renal transplantation have been reviewed here. Where such studies are lacking, the data from less direct studies (e.g. survival of dialysis patients or of the general population) have been considered. Studies of patients without renal failure have not generally been included. Where they are included it will be clearly stated.

Summary of the evidence

The screening of renal transplant candidates for cardiovascular disease is an important consideration, and many, often small studies have been undertaken. There are no randomized controlled trials of screening versus no screening of renal transplant candidates, and the issue does not lend itself to that type of investigation.

The initial screening would usually be clinical, and there is evidence that the absence of clinical risk factors such as age under 50, no diabetes, no angina and a normal ECG helps to define a population at a low risk of post-operative cardiac problems.

Further risk stratification can be achieved with non-invasive testing, including echocardiography, with or without stress and with nucleotide imaging. The role of exercise ECG testing is limited by the reduced exercise capacity of patients with end-stage renal failure. There is little head to head testing of these modalities, and neither is clearly better than the other. The preferred modality will typically depend upon local availability and expertise. In general these investigations should be performed without concurrent beta-blocker therapy in order to achieve a satisfactory heart rate, and it should be noted that the validity of testing is markedly reduced after 24 months.

Coronary angiography is clearly the gold-standard for anatomy, although less clearly for survival information. Exactly which patients require it is not clear from the evidence, but patients with severe abnormalities on screening procedures are at increased risk of cardiac events. Despite this, there is no current evidence that revascularization is beneficial in most instances and current data demonstrate a survival benefit with transplantation compared with staying on dialysis in patients even with substantial coronary artery disease.[10]

Key References

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References
  • 1
    National Vascular Disease Prevention Alliance. Guidelines for the Management of Absolute Cardiovascular Disease Risk. 2012.
  • 2
    Johnson DW, Herzig K, Purdie D et al. A comparison of the effects of dialysis and renal transplantation on the survival of older uremic patients. Transplantation 2000; 69: 794799.
  • 3
    Khauli RB, Steinmuller DR, Novick AC et al. A critical look at survival of diabetics with end-stage renal disease. Transplantation versus dialysis therapy. Transplantation 1986; 41: 598602.
  • 4
    McDonald SP, Russ GR. Survival of recipients of cadaveric kidney transplants compared with those receiving dialysis treatment in Australia and New Zealand, 1991–2001. Nephrol. Dial. Transplant. 2002; 17: 22122219.
  • 5
    Medin C, Elinder CG, Hylander B et al. Survival of patients who have been on a waiting list for renal transplantation. Nephrol. Dial. Transplant. 2000; 15: 701704.
  • 6
    Meier-Kriesche HU, Ojo AO, Port FK et al. Survival improvement among patients with end-stage renal disease: Trends over time for transplant recipients and wait-listed patients. J. Am. Soc. Nephrol. 2001; 12: 12931296.
  • 7
    Ojo AO, Port FK, Wolfe RA et al. Comparative mortality risks of chronic dialysis and cadaveric transplantation in black end-stage renal disease patients. Am. J. Kidney Dis. 1994; 24: 5964.
  • 8
    Rabbat CG, Thorpe KE, Russell JD et al. Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario, Canada. J. Am. Soc. Nephrol. 2000; 11: 917922.
  • 9
    Wolfe RA, Ashby VB, Milford EL et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N. Engl. J. Med. 1999; 341: 17251730.
  • 10
    Jones DG, Taylor AM, Enkiri SA et al. Extent and severity of coronary disease and mortality in patients with end-stage renal failure evaluated for renal transplantation. Am. J. Transplant. 2009; 9: 18461852.

2. Diabetes Mellitus

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References

Guideline recommendations

  1. We recommend that diabetes should not on its own preclude a patient from being considered for kidney transplantation (1D).
  2. We recommend that potential renal transplant candidates with diabetes are screened for cardiovascular disease in accordance with the ‘Cardiovascular Disease’ sub-topic guidelines (1D).
  3. We suggest that renal transplant candidates with diabetes be considered for pre-emptive transplantation due to better patient and graft survival compared with transplantation after the commencement of dialysis (2C).
  4. We suggest that, following screening for cardiovascular disease, Type 1 diabetic transplant candidates should be considered for referral for simultaneous pancreas and kidney transplantation (SPK) or live donor renal transplantation (2B).

Ungraded suggestions for clinical care

  • Kidney transplantation generally offers longer survival than remaining on dialysis for patients with diabetes who have historically been wait-listed for transplantation (ungraded).
  • Diabetes is a multi-system disease, and some of the complications of diabetes can directly impact on the success of transplantation:
    • Consideration should be given to the possibility of diabetic enteropathy, which can reduce the oral absorption of immunosuppressive medications. Patients should be monitored carefully for immunosuppressive drug concentrations and for rejection (ungraded).
    • Consideration should be given to the urological implications of potential neuropathic bladder (ungraded).

Background

Diabetes mellitus is an increasingly common disease in Australia and New Zealand. It is an important cause of renal failure, and a common comorbidity among dialysis and transplant patients. It is associated with increased rates of cardiovascular disease and premature mortality. These factors make diabetes an important consideration in the assessment of patients for renal transplantation. The ‘Cardiovascular Disease’ sub-topic guidelines present recommendations and suggestions in relation to screening and testing for cardiovascular disease.

Suitability for transplantation is a difficult and sometimes imprecise concept. Studies to demonstrate which patients will live longer after a transplant, compared with remaining on dialysis are difficult. Randomization is impossible, inherent biases are inevitable and transplant outcome data can only be obtained for patients who are being transplanted under current acceptance protocols. Furthermore, the potential for an improved quality of life means that there are patients who would enthusiastically embrace an opportunity to attempt transplantation even if the statistics were against their success.

There is little prospect of any studies that will accurately measure the benefit or otherwise of renal transplantation compared with remaining on dialysis, for diabetic patients. Prospective randomized trials are impractical, and retrospective analyses are potentially limited by the under-diagnosis of diabetes among wait-listed patients,[1] and by differences between wait-listed patients who either do or do not receive transplants.[2]

The most informative studies available are a number of retrospective cohort studies, taken from a number of databases, that compare patients who are transplanted with those who are wait listed, but not transplanted, and/or those who are not wait-listed.[3-5] There is also a systematic review of these studies.[6] These studies demonstrate that across a wide range of subgroups, including diabetics, survival is better for patients who are transplanted, than for patients who remain on dialysis.

This guideline reviews the available data about the impact of diabetes mellitus on the outcomes of renal transplantation. The most frequently studied outcomes are patient and graft survival.

Summary of the evidence

Numerous studies suggest that patients with either type 1 or type 2 diabetes have lower patient and graft survival than transplant recipients without diabetes. This reduction in graft survival is less pronounced if death-censored graft survival is considered. There is a higher rate of cardiovascular death in particular among renal transplant recipients with diabetes, and this probably explains a significant part of the difference in outcomes.

Diabetes is a multi-system disease, and some of the complications of diabetes can directly impact on the success of transplantation. It makes intuitive sense to screen transplant candidates with diabetes carefully for evidence of cardiac or other vascular disease, either to inform perioperative risk and management, to allow pre-emptive treatment, or to exclude on the basis of poor predicted outcomes (refer to ‘Cardiovascular Disease’ sub-topic guidelines).

Patients with Type 1 diabetes mellitus, are best served, where possible by simultaneous pancreas and kidney transplantation, or by live donor renal transplantation.

Key References

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References
  • 1
    Hergesell O, Zeier M. Underdiagnosis of diabetes mellitus in chronic dialysis patients on the renal transplant waiting list. Transplant. Proc. 2003; 35: 12871289.
  • 2
    Kyllonen L, Salmela K. Why do some diabetic patients on the kidney transplant waiting list not receive a transplant? Transpl. Int. 2004; 17: 511517.
  • 3
    Brunkhorst R, Lufft V, Dannenberg B et al. Improved survival in patients with type 1 diabetes mellitus after renal transplantation compared with hemodialysis: A case-control study. Transplantation 2003; 76: 115119.
  • 4
    Cecka JM. The UNOS Scientific Renal Transplant Registry. Clin. Transpl. 1996; 114.
  • 5
    Waki K. Impact of diabetes mellitus on transplantation. Clin. Transpl. 2004; 357377.
  • 6
    Tonelli M, Wiebe N, Knoll G et al. Systematic review: Kidney transplantation compared with dialysis in clinically relevant outcomes. Am. J. Transplant. 2011; 11: 20932109.

3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References

Guideline recommendations

Human Immunodeficiency Virus (HIV)
  1. We recommend that HIV infection should not preclude a patient from being assessed for kidney transplantation (1D).
Hepatitis B Virus (HBV)
  1. We recommend that HBV infection should not preclude a patient from being assessed for kidney transplantation (1D).
Hepatitis C Virus (HCV)
  1. We recommend that HCV infection should not preclude a patient from being assessed for kidney transplantation (1D).

Ungraded suggestions for clinical care

HIV
  • Testing for HIV should be performed in all potential kidney transplant candidates (ungraded).
  • Assessment of HIV-infected potential kidney transplant patients should be performed in centres with experience in the management of both HIV infection and kidney transplantation (ungraded).
  • HIV-infected patients may be candidates for kidney transplantation if the following criteria are met (ungraded):
    1. Adherence to a HAART treatment protocol, with no recent change to anti-retrovirals within 3 months.
    2. Undetectable viral load for at least 3 months.
    3. CD4 count >200/μL for at least 6 months.
    4. Patients with no history of a detectable HIV RNA test and who maintain undetectable HIV RNA levels without HAART may be suitable for transplantation.
    5. Some previous opportunistic complications may exclude transplantation.
    6. Other usual kidney eligibility criteria are met.
  • HIV patients coinfected with HCV or HBV may be suitable for kidney transplantation. Both infections should be fully assessed. Those patients with cirrhosis and HCV or HBV coinfection may be considered for a combined liver/kidney transplant in some circumstances (ungraded).
HBV
  • Testing for HBV should be performed in all potential kidney transplant candidates (ungraded).
  • Renal transplant candidates with HBV infection should undergo complete specialist hepatology assessment (ungraded).
  • Potential transplant recipients with decompensated HBV cirrhosis may be considered for a combined liver/kidney transplant (ungraded).
  • Transplant candidates with HBV liver disease should be treated, if suitable (chronic active hepatitis, compensated cirrhosis) (ungraded).
  • Patients with no response to HBV treatment may still be considered for transplantation in some circumstances (ungraded).
HCV
  • Testing for HCV should be performed in all potential kidney transplant candidates (ungraded).
  • The KDIGO clinical practice guideline for the prevention, diagnosis, evaluation and treatment of Hepatitis C in Chronic Kidney Disease[1] provides recommendations and suggestions appropriate to consideration of kidney transplant recipients within Australia and New Zealand (http://www.kdigo.org). Specifically, for the HCV-infected potential kidney transplant recipient;
    1. HCV RNA positive infected patients being considered as candidates for kidney transplantation should undergo specialist hepatology assessment. If suitable treatment with anti-viral medication should be undertaken prior to transplantation (ungraded).
    2. HCV infected patients with cirrhosis and compensated liver disease may be considered for transplantation in some investigational circumstances (ungraded).
    3. HCV infected patients with cirrhosis and decompensated liver disease may be candidates for combined liver/kidney transplantation (ungraded).

Background

Concerns regarding infectious complications exacerbated by immunosuppression after transplantation have led to the widespread screening of all potential renal transplant candidates for evidence of active infection. Often, however, these infections can be adequately managed to allow successful transplantation.[1-3] This guideline was designed to focus on chronic viral infections (HIV, HBV and HCV) which are increasingly recognized amongst potential transplant recipients and may be modified to safely allow transplantation.

This guideline reviews the optimal approach to HIV, HBV and HCV amongst those patients being considered for listing as candidates for renal transplantation. It is focused on these chronic viral infections, in particular, because each has relevant therapeutic interventions which may be undertaken to potentially reduce morbidity and mortality after renal transplantation. It is designed specifically to ensure that all patients with these conditions are considered for renal transplantation, which can improve their clinical outcomes compared with remaining on long-term dialysis.

Summary of the evidence

There is increasing clinical experience and an emerging body of evidence to suggest that potential renal transplant recipients with chronic viral infections (HIV, HBV and HCV) are candidates for transplantation and in many circumstances will have outcomes equivalent to the non-infected population. These excellent outcomes require careful selection of these patients prior to transplantation. This will allow for the optimization of outcomes and a full assessment of the risks and benefits for each patient prior to proceeding with long-term immunosuppression in the setting of a chronic infection.

Because of the nature of this area no randomized controlled trials exist. Additionally, the assessment of the evidence and how it applies to each potential transplant candidate requires knowledge of the up to date developments in the field, with the rapid emergence of new treatments and approaches to management. Newer antivirals, specialized management in the pre- and post-transplant period and other developments mean that this is an emerging and evolving field.

Clearly, patients with HIV, HBV and HCV should be considered as candidates for renal transplantation with careful assessment, management and selection allowing for successful transplantation in many circumstances. Few absolute contraindications to transplantation relating directly to HIV, HBV and HCV remain, and transplantation can improve the prognosis of many of these patients compared with remaining on dialysis.

Key References

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References

4. Malignancy

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References

Guideline recommendations

  • a.
    We recommend that screening for malignancy prior to transplantation be conducted in accordance with usual age and sex appropriate cancer screening policies for the general population (1D).
  • b.
    We recommend that patients with the following malignancy not be transplanted:
    1. Uncontrolled or untreated malignancies (1D).
    2. Multiple Myeloma (1D).
    3. Advanced Breast Cancer (stage III) (1D).
    4. Colorectal Cancer (stage D) (1D).
  • c.
    We suggest that consideration be given to the following minimum waiting periods from successful treatment of malignancy to transplantation (2D).
    Note: Due to limited evidence, the following suggestions are proposed with a view to achieving an 80% likelihood of 5-year patient survival. Decision making will still need to be individualized to account for the specifics of the patient's prior malignancy and their overall medical status.
Nil
    1. Superficial Bladder Cancer (2D).
    2. In situ Cancer of the Cervix (2D).
    3. Non-metastatic Non-Melanoma Skin Cancers (2D).
    4. Prostatic Cancer microscopic (2D).
    5. Asymptomatic T1 Renal Cell Carcinoma with no suspicious histological features (2D).
    6. Monoclonal Gammopathy of Undetermined Significance (2D).

2 years
    1. Invasive Bladder Cancer (2D).
    2. In situ Breast Cancer (2D).
    3. Stage A and B Colorectal Cancer (2D).
    4. Lymphoma (2D).
    5. In situ Melanoma (2D).
    6. Prostatic Cancer (2D).
    7. Testicular Cancer (2D).
    8. Thyroid Cancer (2D).
    9. Wilm's Tumour (2D).

5 years
    1. Stage II Breast Cancer (2D).
    2. Extensive Cervical Cancer (2D).
    3. Colorectal Cancer stage C (2D).
    4. Melanoma (2D).
    5. Symptomatic Renal Cell Carcinoma (2D).
  • d.
    We suggest advising patients with a prior malignancy that they are at increased risk of de novo malignancy post-transplantation compared with those with no prior history of malignancy undergoing transplantation (2B).

Ungraded suggestions for clinical care

None provided.

Background

Prior malignancy in a potential renal transplant recipient is increasingly commonly encountered.[1] This is likely to be due to the increasing age of patients accepted as suitable for renal transplantation. There are limited data available to guide decision making as to the suitability of transplanting patients with a prior malignancy with most information drawn from the work of a single USA-based database.[2-4]

Malignancies are heterogeneous within the same organ as well as between organs and as such have different natural histories and recurrence rates. Therefore, a blanket recommendation for malignancy overall would not be valid but even for a single type of malignancy such as breast cancer, recommendations would ideally be based on the tumour stage, grade and more detailed information such as receptor positivity or other molecular analysis. This level of information is simply not available at the present time. The guidelines are based on a small number of studies primarily of registry data with a consequent high risk of bias and hence presented as suggestions rather than recommendations.

Given the lack of high level evidence and the complexity of risk/benefit analyses in deciding on the suitability of patients for transplantation it is likely that transplantation will be offered to patients outside the above suggestions which were formulated for deceased donor transplantation with a view to an 80% likelihood of 5-year patient survival. Patients with a live donor who are cognizant of the risks involved but retain a firm desire to proceed may be considered in the pursuit of a better quality of life. These decisions clearly require close discussions between recipient, donor, the treating transplant team and an oncologist.

This guideline seeks to provide some suggestions for Nephrologists involved in advising patients with a prior malignancy on waiting times from successful treatment of malignancy to transplantation.

Summary of the evidence

Recommendations are difficult in this area given the lack of sufficient evidence. Most data are from reports on outcomes in less than 100 patients. These reports do not described the malignancies sufficiently in terms of staging or the range of waiting times observed from successful treatment until transplantation to be able to offer a stage by stage suggestion as to waiting times. Therefore, this guideline along with other international guidelines has grouped malignancies together in offering suggestions for waiting times. These should be read in that light as it is likely that a lower grade/stage malignancy may require a shorter duration of waiting than a more aggressive/advanced malignancy.

Overall the suggestions are that in situ or pre-malignant conditions require minimal or no waiting time while for other cancers a 2- or 5-year wait has been suggested on the basis of the reported recurrence rates and associated mortality risks. The suggestions made are based on deceased donor transplant listing with the aim of achieving an 80% chance of 5-year survival although the data do not allow that degree of precision. In patients with a live donor a decision to proceed earlier may be made if all parties are agreeable after understanding the likely risks involved.

Key References

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References
  • 1
    Campbell S, McDonald SP, Webster A et al. Chapter 8: Transplantation, in ANZDATA 2008 Annual Report. 2008.
  • 2
    Penn I. Evaluation of transplant candidates with pre-existing malignancies. Ann. Transplant. 1997; 2: 1417.
  • 3
    Penn I. The effect of immunosuppression on pre-existing cancers. Transplantation 1993; 55: 742747.
  • 4
    Penn I. Cancers in renal transplant recipients. Adv. Ren. Replace. Ther. 2000; 7: 147156.

5. Obesity

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References

Guideline recommendations

  1. We recommend that obesity should not on its own preclude a patient from being considered for kidney transplantation (1B).
  2. As a pretransplant BMI (Body Mass Index) >40 kg/m2 may not be associated with a survival advantage compared to remaining on dialysis, we suggest that the suitability for transplant be carefully assessed on an individual basis (2C).
  3. As patient and graft survival of obese transplant recipients may be mediated by comorbid factors, particularly cardiovascular, we recommend that obese transplant candidates are screened for cardiovascular disease (refer to ‘Cardiovascular Disease’ sub-topic guidelines for recommendations) (1C).

Ungraded suggestions for clinical care

None.

Background

In the past, high BMI as a barrier for transplantation has tended to be a surgical issue. It was recognized as a problem by Starzl's group in 1990.[1] It appears, however, that there are also medical implications in terms of graft and patient loss. In the USA, nearly 58.8% of subjects at the time of transplantation currently are overweight or obese.[2]

Summary of the evidence

Most studies are small, single-centre, control-matched comparisons, and therefore may not be particularly helpful. Some of the earlier studies used different immunosuppression regimens, to those used currently, which may also have an effect.

There are now, however, a number of reports from nationwide databases, including the USA, Australia and the Netherlands, which show that there is decreased patient and graft survival in obese recipients. However, it may be that this risk is diminished if other risk factors, particularly cardiovascular, are taken into account. Whether or not weight loss diminishes the risk of obesity in renal transplantation is unclear.

For the individual patient, a renal transplant is usually better than remaining on dialysis, although this was not true for patients with a BMI > 40 kg/m2 in their study.[3] However, there appears to be some increased risk with obesity.

Key References

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References

6. Paediatric Recipient

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References

Guideline recommendations

  1. In relation to age at the time of transplantation we recommend that:
    • There be no lower age limit set for transplantation (1B).
    • In infants under 1 year of age, transplantation should be performed in highly specialized units with extensive experience in paediatric transplantation (1D).
    • In infants under 1 year of age, adult live donors should be used in preference to cadaveric donors (1C).
  2. In all patients but particularly in adolescents we recommend that:
    • Risk factors for non-adherence are identified prior to transplantation (1D).
    • Specific strategies are implemented to actively manage factors and behaviours that contribute to non-adherence (1D).
  3. We recommend that children with urological abnormalities be carefully assessed prior to transplantation and that abnormalities in bladder emptying are corrected before transplantation (1D).
  4. We suggest that asymptomatic vesicouretic reflux does not require correction prior to transplantation (2C).
  5. We suggest that children with Wilms tumour wait at least 2 years following completion of chemotherapy before undergoing transplantation (2D).
  6. We suggest that post-transplant anticoagulation be considered for children with thrombophilic disorders (2D).
  7. We recommend that mental retardation should not preclude an individual from consideration for transplantation (1C).

Ungraded suggestions for clinical care

None provided.

Background

Renal transplantation is considered the treatment of choice for children with end stage kidney disease with Australasian data showing a four-fold risk of death in children who remain on dialysis compared with those who are transplanted.[1] Kidney transplants are now performed routinely in many paediatric centres around the world with excellent reported graft (1- and 5-year graft survival up to 95%) and patient survival (5- and 10-year patient survival of 70–100% and 75–95%, respectively).[2, 3] A number of studies have shown the important benefits of transplant in improving cognitive development[4-6] and growth[7] of children. In recognition of these unique benefits of transplant to children and adolescents, many countries including Australia give priority to paediatric recipients on deceased donor waiting lists in order to expedite transplantation and keep waiting time short.[3, 8, 9]

Absolute contraindications to kidney transplantation in children and adolescents are not significantly different to adult transplantation and include unmodifiable immunological incompatibility, active infection, malignancy or substance abuse. In some genetic conditions, combined organ transplantation (e.g. liver–kidney transplantation) should be considered as the treatment of choice. Additional factors that may impact on paediatric recipient suitability are discussed in more detail below.

Summary of the evidence

Transplantation is the primary goal for children with end stage kidney disease and results in improvements in growth, physical and intellectual development. Data from a number of case series show that there is no younger age limit to transplantation, although it is recommended that transplantation of infants under 1 year of age be performed in highly specialized units with extensive experience in paediatric transplantation. While poor adherence remains a significant cause of graft failure in the adolescent age group, delaying transplantation may be associated with poorer outcomes and is not recommended. Children with urological abnormalities require careful pretransplant assessment with consideration given to correction of bladder abnormalities prior to transplantation. Other comorbid conditions such as obesity, mental retardation and haemostatic defects should not be considered a contraindication to transplantation.

Key References

  1. Top of page
  2. 1. Cardiovascular Disease
  3. Key References
  4. 2. Diabetes Mellitus
  5. Key References
  6. 3. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
  7. Key References
  8. 4. Malignancy
  9. Key References
  10. 5. Obesity
  11. Key References
  12. 6. Paediatric Recipient
  13. Key References

*Explanation of grades

The evidence and recommendations in this KHA-CARI guideline have been evaluated and graded following the approach detailed by the GRADE working group (http://www.gradeworkinggroup.org). A description of the grades and levels assigned to recommendations is provided in Tables 1 and 2.

Table 1. Final grade for overall quality of evidence
Overall Evidence GradeDescription
A

High quality of evidence.

We are confident that the true effect lies close to that of the estimate of the effect.

B

Moderate quality of evidence.

The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

C

Low quality of evidence.

The true effect may be substantially different from the estimate of the effect.

D

Very low quality of evidence.

The estimate of effect is very uncertain, and often will be far from the truth.

Table 2. Nomenclature and description for grading recommendations
GradeImplications
PatientsCliniciansPolicy
Level 1 ‘We recommend’Most people in your situation would want the recommended course of action and only a small proportion would notMost patients should receive the recommended course of actionThe recommendation can be adopted as a policy in most situations
Level 2 ‘We suggest’The majority of people in your situation would want the recommended course of action, but many would notDifferent choices will be appropriate for different patients. Each patient needs help to arrive at a management decision consistent with her or his values and preferencesThe recommendation is likely to require debate and involvement of stakeholders before policy can be determined

**Access to the full text version

For a full-text version of the guideline, readers need to go to the KHA-CARI website (go to the Guidelines section (http://www.cari.org.au)).