The Renal Association

These guidelines address access to transplantation, together with the evaluation, selection and preparation of the potential transplant recipient. Future guidelines will address post-transplant care. Readers should refer to the joint British Society for Histocompatibility and Immunogenetics/British Transplantation Society document for guidelines on the detection and characterization of HLA antibodies in renal transplantation (www.bts.org.uk/standards.htm).

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SUMMARY OF CLINICAL PRACTICE GUIDELINES

1. Assessment for transplantation (Tx) (Guidelines 1.1 - 1.9)

Guideline 1.1 - Tx : Access to renal transplantation

Kidney transplantation should be the renal replacement therapy of choice for patients with chronic kidney disease stage 5 who are considered fit for major surgery and for chronic immunosuppression. All patients predicted to have an increased life expectancy post-transplantation should be assessed for transplantation. Placement on the transplant waiting list will be limited by individual co-morbidity and prognosis.

Living donor transplantation should be considered the treatment of choice for all patients suitable for renal transplantation when there is an appropriate donor.

Patients with progressive deterioration in renal function suitable for transplantation should be placed on the national transplant list within six months of their anticipated dialysis start date. Pre-emptive transplantation should be the treatment of choice for all suitable patients whenever a living donor is available.

There must be demonstrable equity of access to deceased donor kidney transplantation irrespective of gender, ethnicity or district of residence.

Age is not a contra-indication to transplantation but age related co-morbidity is an important limiting factor.

All transplant units should have written criteria for acceptance on to the waiting list. The benefits and potential risks associated with transplantation should be fully explained both verbally and in writing. Potential transplant recipients should be informed of all donor options including living related and unrelated donation.

All CKD 5 patients and CKD 4 patients with progressive disease should have their suitability for transplantation assessed annually and appropriate patients should be referred to a transplant centre. When transplantation is considered inappropriate the reason(s) should be documented. Patients should be placed on, or removed from the waiting list only after discussion and agreement with the nephrologist, transplant surgeon and the patient themselves according to local practice.

The care of the renal transplant recipient is best undertaken by a multi-disciplinary team.

Simultaneous kidney-pancreas transplantation or living donor renal transplantation is the treatment of choice for patients with Type 1 diabetes mellitus who are suitable for renal transplantation.

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2. Assessment for transplantation (Tx) (Guidelines 2.1 - 2.9)

Guideline 2.1 - Tx : Pre-transplant cardiac assessment

The object of pre-transplant assessment is: a) to ensure transplantation is technically possible b) to ensure the recipient’s chances of survival are not compromised by transplantation c) to ensure that graft survival is not limited by premature death (maximum benefit obtained from a limited resource) d) to ensure pre-existing conditions are not exacerbated by transplantation e) to identify measures to be taken to minimise peri- and post-operative complications f) to inform patients of likely risks and benefits of transplantation.

Although controversial, current evidence suggests that patients should have a cardiac stress test performed as part of their assessment for transplantation if: 1) they are more than 49 years old, 2) they have diabetes mellitus, 3) they have an abnormal ECG (other than LVH), 4) they have a history of ischaemic heart disease, CCF, peripheral vascular disease or ischaemic cerebrovascular disease. Patients unable/unlikely to achieve their maximum predicted work load on exercise ECG should have dipyridamole-thallium imaging (or similar), stress echocardiography or coronary angiography according to local cardiological advice. If possible stress testing should be performed without concurrent beta-blocker therapy. Patients with a positive cardiac stress test should be considered high risk for a cardiac event and should not be offered transplantation until further cardiac evaluation or treatment has been undertaken.

The use of pre-operative beta-blockers may be considered in patients at high cardiovascular risk undergoing renal transplantation. Low dose aspirin therapy is not a contraindication to transplantation and can be continued peri-operatively.

Guideline 2.4 - Tx : Preparation of the renal transplant recipient

Patients should be strongly encouraged to stop smoking before and after transplantation. Formal smoking cessation programmes should be offered and accessed in primary care.

Obese patients (BMI >30) present technical difficulties and are at increased risk of peri-operative complications. They should be screened rigorously for cardiovascular disease and each case considered individually. Although obesity is not an absolute contra-indication to transplantation, individuals with a BMI >40 kg/m² are less likely to benefit.

Guideline 2.6 - Tx : Preparation of the renal transplant recipient

All potential transplant recipients should be tested for prior exposure to viral infections including: cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), hepatitis B and C and human immunodeficiency virus (HIV). Immunization should be offered to all hepatitis B (if not already immunized) and VZ virus antibody negative patients before transplantation. Patients otherwise suitable for renal transplantation with evidence of chronic hepatitis B and/or C or HIV infection should be managed according to British Transplantation Society and European Best Practice Guidelines prior to transplantation.

Guideline 2.7 - Tx : Evaluation and selection of the renal transplant recipient

In potential recipients with previous malignancy (excluding non-melanoma skin cancer), renal transplantation should only be considered if there is no evidence of persistent cancer. It is recommended that the waiting time between successful tumour treatment/remission and transplantation be at least 2 years. For certain malignancies the waiting time may need to be extended to more than 5 years. The Israel Penn International Transplant Tumor Registry should be consulted for tumour specific advice (www.ipittr.uc.edu/Home.cfm).

Patients who are at risk of developing recurrence of original renal disease should be managed according to the European Best Practice Guidelines (EBPG).

There is no evidence that asymptomatic potential transplant recipients require screening for diverticular disease, peptic ulceration or gall bladder stones.

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SUMMARY OF AUDIT MEASURES

1. The proportion of patients with and without diabetes mellitus < 65 years old with CKD stage 5 listed for transplantation
2. The proportion of transplant patients who receive a living donor transplant
3. The time to placement on the UK Transplant national transplant list in relation to start date of dialysis
4. The proportion of living donor transplant recipients transplanted before starting dialysis
5. A comparison between renal units of the proportion of dialysis patients placed on the national transplant list corrected for differences in identified unit and patient specific variables including co-morbidity.
6. The proportion of CKD stage 5 patients with a transplant status recorded.
7. The proportion of CKD stage 5 dialysis patients with Type 1 diabetes mellitus listed for simultaneous kidney-pancreas transplantation
8. The proportion of patients >49 years old or with diabetes mellitus listed for transplantation who have had a cardiac assessment
9. The proportion of patients who smoke (or have given up within the last year) a) whilst listed for transplantation b) one year after renal transplantation
10. The proportion of obese patients (BMI >30) on the transplant waiting list who have had a cardiac assessment.
11. The number of patients with BMI >40 kg/m² who are on the transplant waiting list and the reason for their inclusion.
12. The proportion of patients on the transplant waiting list whose viral status is known for CMV, EBV, VZV, hepatitis B and C and HIV.
13. The proportion of VZV and HBc antibody negative patients on the transplant waiting list who have been immunized against these viruses.

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FULL CLINICAL PRACTICE GUIDELINES

1. Assessment for transplantation (Tx) (Guidelines 1.1 - 1.9)

Guideline 1.1 - Tx : Access to renal transplantation

Kidney transplantation should be the renal replacement therapy of choice for patients with chronic kidney disease stage 5 who are considered fit for major surgery and for chronic immunosuppression. All patients predicted to have an increased life expectancy post-transplantation should be assessed for transplantation. Placement on the transplant waiting list will be limited by individual co-morbidity and prognosis. (Good practice)

Audit measure

The proportion of patients with and without diabetes mellitus < 65 years old with CKD stage 5 listed for transplantation.

Rationale

Survival following renal transplantation is better compared to age-matched individuals remaining on the transplant waiting list¹. In a series of 46,164 patients on the transplant waiting list in the USA between 1991-1997 mortality was 68% lower for transplant recipients than for those remaining on the transplant waiting list for >3 yrs follow-up.¹ This resulted in a mean increase in projected survival of 10 years maximized in the 20-39 year old age group who were predicted to live 17 years longer than their counterparts remaining on the transplant waiting list. The increased survival benefit was seen in both sexes and was even more marked in diabetics. This analysis was, of course, confined to those patients admitted to the waiting list using the criteria for fitness for transplantation in use at the time of the study in the USA, and therefore cannot safely be extrapolated to higher risk potential transplant candidates. Although a smaller study from Scotland replicated these findings, a similar more recent analysis from the UK showed that patients over the age of 65 years did not experience any survival advantage compared with matched patients who were listed but not transplanted^2,3.

References

1. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LYC, Held PJ, Port FK. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation and recipients of a first cadaveric transplant. New Eng J Med 1999; 341: 1725-30.
2. Oniscu GC, Brown H, Forsythe, JLR. Impact of cadaveric renal transplantation on survival in patients listed for transplantation. J Am Soc Nephrol 2005; 16: 1859-65
3. Dudley C, Start S, Johnson R, O’Neill J, Collett D, Ansell D. BTS Congress 2007.

Guideline 1.2 - Tx : Access to renal transplantation

Living donor transplantation should be considered the treatment of choice for all patients suitable for renal transplantation when there is an appropriate donor (Good practice)

Audit measure

The proportion of transplant patients who receive a living donor transplant

The demand for renal transplantation has consistently and increasingly outstripped the number of available deceased donor organs for the last 20 years. In 2005 this shortfall had increased to almost 6000 patients¹. Donation of a kidney from a live donor is the most realistic option to expand organ donation². Living donor kidney transplantation provides most patients with the best chance of long-term rehabilitation. It also facilitates access to deceased donor transplantation for those without a living donor. The opportunity for planned transplantation before dialysis is required is an attractive option for patients and evidence suggests that there is improved graft survival of transplants performed pre-emptively³. During the last 5 years there has been substantial increase in living donor kidney transplantation in the UK with almost 1 in 3 of all renal transplants being performed from living donors in 2005 (living donor kidney transplantation rate 9.2 per million population pmp). However, there is still considerable room for expansion in comparison with activity in Scandinavia (12.9 pmp) and the USA. Living kidney donation also enables scheduling of transplantation at a time when the recipient is in optimal medical and psychological condition and may be the only option in high-risk recipients.

References

1. www.uktransplant.org.uk/ukt/statistics/statistics.jsp
2. Ingelfinger JR. Risks and benefits to the living donor. N Engl J Med 2005; 353:447-9
3. Meier-Kriesche HU, Kaplan B. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes. Transplantation 2002; 74(10): 1377-1381.

Guideline 1.3 - Tx : Access to renal transplantation

Patients with progressive deterioration in renal function suitable for transplantation should be placed on the national transplant list within six months of their anticipated dialysis start date. Pre-emptive transplantation should be the treatment of choice for all suitable patients whenever a living donor is available. (Evidence)

Audit measure a): The time to placement on national transplant list in relation to start date of dialysis b): The proportion of living donor transplant recipients transplanted before starting dialysis

Rationale

In a series of 38,836 first kidney transplants in the USA between 1995-8, pre-emptive transplantation was associated with 25% reduction in graft failure and 16% reduction in mortality in recipients of deceased donor kidneys¹. In pre-emptive living related transplant recipients there was a 31% reduction in mortality and a 27% reduction in graft failure compared to recipients receiving a transplant when already established on dialysis¹. Transplant survival is negatively influenced by duration of dialysis before transplantation, with a 5 year allograft survival of approximately 85% in pre-emptive transplantation compared with 75% in those receiving dialysis for 3-4 years before transplantation². Patients with advanced CKD should receive a renal transplant as soon as possible to optimize clinical outcomes. Under Standard Two of The National Service Framework for Renal Services (Part One) a marker of good practice is the placement of patients on the national transplant list within six months of their anticipated dialysis start date if clinically appropriate³.

References

1. Kasiske BL, Snyder JJ, Matas MD, Ellison MD, Gill JS, Kausz AT. Pre-emptive kidney transplantation: The advantage and the advantaged. J Am Soc Nephrol 2002; 13: 1358-64.
2. Meier-Kriesche HU, Port FK, Ojo AO, Rudich SM, Hanson JA, Cirik DM, Leichtman AB, Kaplan B. Effect of waiting time on renal transplant outcome. Kidney Int 2000; 58: 1311-7.
3. The National Service Framework for Renal Services (Part One: Dialysis and Transplantation), Department of Health, January 2005

Guideline 1.4 - Tx : Access to renal transplantation

There must be demonstrable equity of access to deceased donor kidney transplantation irrespective of gender, ethnicity or district of residence. (Good practice)

Audit measure

A comparison between renal units of the proportion of dialysis patients placed on the national transplant list corrected for differences in identified unit and patient specific variables including co-morbidity.

Rationale

Renal transplantation remains the most successful and cost effective treatment for suitable patients with end stage renal disease (ESRD). Not all patients receiving dialysis are suitable for kidney transplantation and there is evidence that selection criteria vary widely throughout the UK^1,2,3. At the beginning of 2004, 23.3% of all patients treated with dialysis were active on the national transplant waiting list. UK Transplant (UKT) coordinates deceased-donor kidney allocation according to a nationally agreed algorithm. In 2004, the UK Transplant Kidney and Pancreas Advisory Group commissioned an Equity of Access Task Force to identify factors that may lead to inequity of access to renal transplant waiting lists, to recommend methods through which unjustified inequity may be removed and to determine methods through which this could be identified. The report from this Task Force contributed in part to the development and implementation of a new national renal allocation algorithm in 2006. A key recommendation from this group was the above audit measure⁴.

1. McMillan MA, Briggs JD. Survey of patient selection for cadaveric transplantation in the United Kingdom. Nephrol Dial Transplant 1995; 10: 855-858
2. Oniscu GC, Schalkwijk AA, Johnson RJ, Brown H, Forsythe JL. Equity of access to renal transplant waiting list and renal transplantation in Scotland: cohort study. BMJ. 2003; 327(7426):1261
3. Dudley C, Johnson RJ, Thomas K, Thomas H, Bakran A, Ansell D. Joint Analyses with UK Transplant in England and Wales UK Renal Registry Report 2005; 5: 69-85
4. UKT KPAG Equity of Access Task Force. Overview Report 2006 RTSM (06)2

Guideline 1.5 - Tx : Access to renal transplantation

Age is not a contra-indication to transplantation but age related co-morbidity is an important limiting factor (Good practice)

Rationale

There is an imbalance between the availability of donor organs and demand for renal transplantation in the UK¹. The shortfall of deceased donor organs has resulted in the national allocation scheme - coordinated by UK Transplant. New allocation criteria are being introduced in a phased manner (2006-8) to minimize racial and geographical inequities². Population studies have shown reduced rates of access to transplantation for African Americans in the USA and British Asians in the UK^3,4.

There is evidence that selection criteria for placement on the transplant waiting list vary significantly throughout the UK⁵. It is important that centres managing patients with Stage 4 and 5 CKD follow standardized procedures for evaluation of suitability for transplantation. Each transplant centre should have written protocols for transplant assessment consistent with European and North American Guidelines^6,7. Improved life expectancy of first deceased donor transplant recipients over patients remaining on the waiting list is seen in all age groups in a US study⁸. Transplant recipients between ages 60-74 had a 61% reduction in mortality and increased predicted survival of 4.3 years over matched patients remaining on the transplant waiting list⁸. In contrast, in a recent UK analysis, patients over the age of 65 years did not experience any survival advantage compared with matched patients who were listed but not transplanted over 5 years of follow-up⁹. Quality of life, however, may be improved. Potential recipients aged 50 or greater should have a careful evaluation of cardiovascular co-morbidity.

References

1. www.uktransplant.org.uk/ukt/statistics/statistics.jsp
2. www.uktransplant.org.uk/ukt/about_transplants/organ_allocation/kidney_(renal)/kidney_(renal).jsp
3. Kasiske BL, Snyder JJ, Matas AJ, Ellison MD, Gill JS, Kausz AT. Pre-emptive kidney transplantation: The advantage and the advantaged. J Am Soc Nephrol 2002; 13: 1358-64
4. Jeffrey RF, Woodrow G, Mahler J, Johnson R, Newstead CG. Indo-Asian experience of renal transplantation in Yorkshire: results of a 10-year survey. Transplantation. 2002 May 27;73(10):1652-7.
5. Dudley C, Johnson RJ, Thomas K, Thomas H, Bakran A, Ansell D. Joint Analyses with UK Transplant in England and Wales UK Renal Registry Report 2005; 5: 69-85
6. Kasiske BL, Cangro CB, Hariharan S, Hrick DE, Kerman RH, Roth D, Rush, DN, Vazquez MA, Weir M. The evaluation of renal transplant candidates: clinical practice guidelines. Am J Transpl 2001; 1: Suppl 2
7. Berthoux F, Abramowicz D, Bradlet B, Ekberg H, Frei U, Morales J, Olgaard K, Paul L, Ponticelli C. European best practice guidelines for renal transplantation ( Part 1). Nephrol Dial Transpl 2000; 15: Suppl 7
8. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LYC, Held PJ, Port FK. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation and recipients of a first cadaveric transplant. New Eng J Med 1999; 341: 1725-30
9. Dudley C, Start S, Johnson R, O’Neill J, Collett D, Ansell D. BTS Congress 2007

Guideline 1.6 - Tx : Access to renal transplantation

All transplant units should have written criteria for acceptance on to the waiting list. The benefits and potential risks associated with transplantation should be fully explained both verbally and in writing. Potential transplant recipients should be informed of all donor options including living related and unrelated donation. (Good practice).

Rationale

It is important that all potential transplant recipients should receive comprehensive information on the risks of transplantation, the results compared with dialysis and the options in terms of different types of donor. All patients should receive education about all forms of living donor transplantation.

Guideline 1.7 - Tx : Access to renal transplantation

All CKD 5 patients and CKD 4 patients with progressive disease should have their suitability for transplantation assessed annually and appropriate patients should be referred to a transplant centre. When transplantation is considered inappropriate the reason(s) should be documented. Patients should be placed on, or removed from the waiting list only after discussion and agreement with the nephrologist, transplant surgeon and the patient themselves according to local practice. (Good practice)

Audit measure

The proportion of CKD stage 5 patients with a transplant status recorded.

Rationale

Clinical practice differs from centre to centre with regard to selection for transplantation¹. It is important to review all patients with stage 4 and 5 CKD as potential transplant recipients according to local protocols following national and European Guidelines². Limitation of access to transplantation by age, gender, social and ethnic background is unacceptable and must be prevented by a standardized assessment mechanism.

The median waiting time to transplantation in the UK for adult patients registered on the kidney transplant waiting list during 2001-2004 was 902 days³. CKD is associated with accelerated cardiovascular disease⁴ requiring regular review of patients on the waiting list for > 2 years to detect emerging co-morbidities which may compromise outcomes of renal transplantation. Surveillance for cardiovascular disease may need to be more frequent in high risk groups such as individuals with previous cardiac intervention or re-transplantation candidates.

References

1. McMillan MA, Briggs JD. Survey of patient selection for cadaveric transplantation in the United Kingdom. Nephrol Dial Transplant 1995; 10: 855-858
2. Berthoux F, Abramowicz D, Bradlet B, Ekberg H, Frei U, Morales J, Olgaard K, Paul L, Ponticelli C. European best practice guidelines for renal transplantation ( Part 1). Nephrol Dial Transpl 2000; 15: Suppl 7
3. http://www.uktransplant.org.uk/ukt/statistics/centre-specific_reports/centre-specific_reports.jsp Accessed on 24 October 2007
4. Levin A, Foley RN. Cardiovascular disease in chronic renal insufficiency. Am J Kidney Dis 2000; 36: S24-S30

Guideline 1.8 - Tx : Access to renal transplantation

The care of the renal transplant recipient is best undertaken by a multi-disciplinary team. The supporting role of transplant nurse specialists in living donor/recipient preparation and recipient care is highly desirable. (Good practice)

Rationale

Optimal early and maintenance care post-transplantation requires close co-operation between health care professionals of different disciplines including H&I scientist, transplant surgeon, nephrologist, anaesthetist, radiologist, histopathologist, renal pharmacist and specialist in infectious disease. Nurse practitioners are increasingly providing a pivotal role in transplant assessment and subsequent co-ordination of maintenance transplant recipients^1,2.

References

1. Burnapp L. Living donor transplantation: Impact of patient focused care on donor outcomes. EDTNA ERCA 1998:24(2):11
2. Short CD, Russell S, Valentine A. Clinical audit and long-term evaluation of renal transplant recipients. Transplantation 2001; 72:S94-8.

Guideline 1.9 - Tx : Access to renal transplantation

Simultaneous kidney-pancreas transplantation or living donor renal transplantation are the treatments of choice for patients with Type 1 diabetes mellitus. (Good practice)

Audit measure

The proportion of CKD stage 5 dialysis patients with Type 1 diabetes mellitus listed for simultaneous kidney-pancreas transplantation

Rationale

In diabetic patients, kidney transplantation leads to a marked improvement in patient and graft survival over continued dialysis¹. A number of studies have demonstrated improved survival for diabetic recipients of simultaneous kidney-pancreas (SPK) transplants compared with deceased donor kidney transplants alone (KA)^2,3. Furthermore, US Registry data suggest that diabetic recipients of deceased donor SPK and living donor KA transplants have similar 5 year mortality risks that are significantly better than that of diabetic recipients of deceased donor KA transplants⁴. All these studies are potentially flawed by selection bias and re-analysis of the UNOS database after correction for differences in donor and recipient risk factors gives similar short-term patient and graft survival between recipients of SPK and KA transplants⁵. However, some studies show that recipients of SPK transplants report better physical health and quality of life in areas that are diabetes specific compared with recipients of KA transplants^6,7, Furthermore, there is accumulating, but as yet inconclusive, evidence that pancreas transplantation may halt and potentially improve some of the long-term complications of diabetes mellitus including retinopathy⁴, nephropathy⁵ and neuropathy⁶.

References

1. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LYC, Held PJ, Port FK. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation and recipients of a first cadaveric transplant. New Eng J Med 1999; 341:1725-30
2. Smets YF, Waeterndorp RG, van der Pijl JW et al. Effect of simultaneous pancreas-kidney transplantation on mortality of patients with type-1 diabetes mellitus and end-stage renal failure. Lancet 1999; 353: 1915-1919
3. Sollinger HW, Odorico JS, Knechtle SJ, D’Alessandro AM, Kalayoglu M, Pirsch JD. Experience with 500 simultaneous pancreas-kidney transplants Ann Surg 1998; 228: 284-296
4. Ojo AO, Meier-Kriesche HU, Hanson JA, Leichtman A, Magee JC, Cibrik D, Wolfe RA, Port FK, Agodoa L, Kaufman DB, Kaplan B. The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. Transplantation. 2001; 71(1):82-90
5. Bunnapradist S, Cho YW, Cecka JM, Wilkinson A, Danovitch GM. Kidney allograft and patient survival in type I diabetic recipients of cadaveric kidney alone versus simultaneous pancreas kidney transplants: a multivariate analysis of the UNOS database. J Am Soc Nephrol. 2003;14(1):208-13
6. Gross CR, Limwattananon C, Matthees B, Zehrer JL, Savik K. Impact of transplantation on quality of life in patients with diabetes and renal dysfunction. Transplantation. 2000;70(12):1736-46
7. Adang EM, Engel GL, van Hooff JP, Kootstra G. Comparison before and after transplantation of pancreas-kidney and pancreas-kidney with loss of pancreas - a prospective controlled quality of life study. Transplantation. 1996; 62(6):754-8
8. Chow VC, Pai RP, Chapman JR et al. Diabetic retinopathy after combined kidney-pancreas transplantation. Clin Transplant 1999; 13: 356-362
9. Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M,. Reversal of lesions of diabetic nephropathy after pancreas transplantation. New Eng J Med 1998; 339: 69-75
10. Cashion AK, Hathaway DK, Milstead EJ, Reed L, Gaber AO. Changes in patterns of 24-hr heart rate variability after kidney and kidney-pancreas transplant. Transplantation 1999; 68: 1846-1850

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2. Assessment for transplantation (Tx) (Guidelines 2.1 - 2.9)

Guideline 2.1 - Tx : Pre-transplant assessment

The object of pre-transplant assessment is: a) to ensure transplantation is technically possible b) to ensure the recipient’s chances of survival are not compromised by transplantation c) to ensure that graft survival is not limited by premature death (maximum benefit obtained from a limited resource) d) to ensure pre-existing conditions are not exacerbated by transplantation e) to identify measures to be taken to minimise peri- and post-operative complications f) to inform patients of likely risks and benefits of transplantation. (Good practice)

Rationale

The main goal of renal transplantation is to improve the life expectancy and quality of life of patients with established renal failure. It follows therefore, that patients who are predicted to have their lives shortened by transplantation or to experience a worsening quality of life should be excluded from the transplant waiting list. It is acknowledged that making such predictions is often difficult and imprecise and that the quality of data to support rational decision making is generally inadequate. There is evidence that selection criteria vary widely throughout the UK as reflected by variation in the proportion of patients who are on the transplant waiting list at different renal units¹. The British Transplantation Society and Renal Association published in July 2003 waiting list criteria for potential renal transplant recipients based, with some minor modifications, on the European Best Practice Guidelines (2000)². The major difference was in the exclusion of patients with a predicted survival of less than 5 years compared with 2 years in the EBPG. The general principles of the pre-transplant assessment listed above are not controversial and constitute best practice. However, the exact mechanism by which some of the individual objectives may be met remain unclear and inevitably results in an element of subjectivity.

References

1. Dudley C, Johnson RJ, Thomas K, Thomas H, Bakran A, Ansell D. Joint Analyses with UK Transplant in England and Wales UK Renal Registry Report 2005; 5: 69-852
2. www.bts.org.uk

Guideline 2.2 - Tx : Pre-transplant cardiac assessment

Although controversial, current evidence suggests that patients should have a cardiac stress test performed as part of their assessment for transplantation if: 1) they are more than 49 years old, 2) they have diabetes mellitus, 3) they have an abnormal ECG (other than LVH), 4) they have a history of ischaemic heart disease, CCF, peripheral vascular disease or ischaemic cerebrovascular disease. Patients unable/unlikely to achieve their maximum predicted work load on exercise ECG should have dipyridamole-thallium imaging (or similar), stress echocardiography or coronary angiography according to local cardiological advice. Where possible stress testing should be performed without concurrent beta-blocker therapy. Patients with a positive cardiac stress test should be considered high risk for a cardiac event and should not be offered transplantation until further cardiac evaluation or treatment has been undertaken.. (Good practice)

Audit measure

The proportion of patients >49 years old or with diabetes mellitus listed for transplantation who have had a cardiac assessment.

Rationale

As cardiovascular disease is the main cause of death after transplantation, careful evaluation for significant coronary artery disease is mandatory. Furthermore, nearly half of all deaths with a functioning graft that occur within 30 days after transplantation are due to ischaemic heart disease, mainly acute myocardial infarction¹. Age, diabetes mellitus and pre-existing coronary artery/peripheral vascular disease are factors that identify individuals at a higher risk of cardiac mortality after transplantation^2-4. This is an important area of controversy without a satisfactory evidence base and further research is required to guide practice. However, current opinion advises that patients who are 50 years or older, have diabetes mellitus, an abnormal ECG (other than LVH), a history of ischaemic heart disease, CCF, peripheral vascular disease or ischaemic cerebrovascular disease should undergo an appropriate non-invasive cardiac stress test⁵. Because many patients with CKD have limited exercise capacity, achieving an adequate exercise ECG may not be possible. In these cases, stress testing with dipyridamole-thallium/sestamibi imaging (or similar), stress echocardiography or coronary angiography is appropriate^{2, 6-11}. Where possible this testing should be performed without concurrent beta-blocker therapy¹². Some studies have suggested that thallium/sestamibi imaging may add little to other clinical information in the evaluation of surgical risk in non-ERF patients¹³. However, the use of thallium/sestamibi imaging may be reasonable in a high risk population such as ERF patients with a high pretest probability of cardiac events¹⁴. Local availability and expertise should be considered when selecting test modalities. Whether screening and subsequent intervention in high-risk patients is effective in preventing future cardiac events or reducing mortality after transplantation is uncertain^15-16. Screening tests may be best used to identify high-risk patients for exclusion from the transplant waiting list.

References

1. Ojo AO, Hanson JA, et al. Long-term survival in renal transplant recipients with graft function. Kidney International 2000; 57: 307-313
2. Le, A., R. Wilson, et al. Prospective risk stratification in renal transplant candidates for cardiac death. American Journal of Kidney 1994; 24(1): 65-71
3. Humar A, Kerr AR, et al. Peri-operative cardiac morbidity in kidney transplant recipients: incidence and risk factors. Clinical Transplantation 2001; 15: 154-158
4. Lentine, K. L., D. C. Brennan, et al. Incidence and Predictors of Myocardial Infarction after Kidney Transplantation. J Am Soc Nephrol 2005; 16(2): 496-506
5. Lewis MS, Wilson RA, et al. Factors in cardiac risk stratification of candidates for renal transplant. Journal of Cardiovascular Risk 1999; 6(4): 251-255
6. Reis G, Marcovitz PA, et al. Usefulness of dobutamine stress echocardiography in detecting coronary artery disease in end-stage renal disease. American Journal of Cardiology 1995; 75(10): 707-710.
7. Dahan M, Viron BM, et al. Diagnostic accuracy and prognostic value of combined dipyridamole-exercise thallium imaging in hemodialysis patients. Kidney International 1998; 54(1): 255-262.
8. Herzog, C., T. Marwick, et al. Dobutamine stress echocardiography for the detection of significant coronary artery disease in renal transplant candidates. American Journal of Kidney Diseases 1999; 33(6): 1080-1090
9. Mistry BM, Bastani B, et al. Prognostic value of dipyridamole thallium-201 screening to minimize perioperative cardiac complications in diabetics undergoing kidney or kidney-pancreas transplantation. Clinical Transplantation 1998; 12(2): 130-135
10. West JC, Napoliello DA, et al. Preoperative dobutamine stress echocardiography versus cardiac arteriography for risk assessment prior to renal transplantation. Transplant International 2000; 13(Suppl 1): S27-30
11. Rabbat CG, Treleaven DJ, et al. Prognostic value of myocardial perfusion studies in patients with end-stage renal disease assessed for kidney or kidney-pancreas transplantation: a meta-analysis. Journal of the American Society of Nephrology 2003; 14: 431-439
12. Holley JL, Fenton RA, et al. Thallium stress testing does not predict cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. American Journal of Medicine 1991; 90(5): 563-570
13. Mangano DT, London MJ, et al. Dipyridamole thallium-201 scintigraphy as a preoperative screening test - a re-examination of its predictive potential. Circulation 1991; 84: 493-502
14. Kasiske B, Cangro CB, et al. The Evaluation of the Renal Transplant Candidates: Clinical Practice Guidelines." American Journal of Transplantation 2001; 1(s2): 1-95
15. Kasiske BL, Malik MA, et al. Risk-Stratified Screening for Ischemic Heart Disease in Kidney Transplant Candidates. Transplantation 2005; 80(6): 815-820
16. McFalls, E. O., H. B. Ward, et al. Coronary-Artery Revascularization before Elective Major Vascular Surgery. N Engl J Med 2004; 351(27): 2795-2804

Guideline 2.3 - Tx : Preparation of the renal transplant recipient

The use of pre-operative beta-blockers may be considered in patients at high cardiovascular risk undergoing renal transplantation. Low dose aspirin therapy is not a contraindication to transplantation and can be continued peri-operatively. (Good practice)

Rationale

Despite recommendations by a number of guideline committees for the use of beta-blockers in high-risk patients undergoing non-cardiac surgery to prevent peri-operative cardiovascular events, evidence of the efficacy of this approach from randomised clinical trials is limited^1-2. Meta-analyses that have included and excluded different trials have reached different conclusions. The most recent meta-analysis has concluded that although peri-operative beta-blockers may decrease the risk of major peri-operative cardiovascular events, their use increases the risk of bradycardia and hypotension needing treatment and that the evidence for their use was insufficient and inconclusive³. A large US cohort study in which the outcome of patients undergoing non-cardiac surgical procedures was analysed according to whether or not they received beta-blockers within the first 2 days of hospitalization concluded that high-risk patients who received beta-blockers were significantly less likely to die in hospital. However, low risk patients receiving beta-blockers were more likely to die⁴. The recently published guideline update from the American College of Cardiology/American Heart Association provides sensible advice on peri-operative beta-blocker use based on the current published evidence⁵. The guidelines state that beta-blockers are probably recommended for patients undergoing intermediate- or high-risk surgical procedures whose pre-operative assessment identifies coronary heart disease or high cardiac risk. To avoid peri-operative bradycardia and hypotension it would be prudent to start beta-blockers at least one month prior to transplantation.

Aspirin has a major role in the primary and secondary prevention of myocardial infarction and reduces the severity of silent myocardial ischaemia in both stable and unstable angina. Perioperative aspirin therapy is associated with a significant reduction in mortality in patients undergoing coronary bypass surgery and is not associated with an increased risk of bleeding or gastritis⁶. It interferes with platelet aggregation induced by thromboxane A₂ but not by either thrombin or high concentrations of collagen. Therefore, clinically significant bleeding should not be made worse by perioperative aspirin⁷. Furthermore, the use of low dose peri-operative aspirin may reduce the risk of transplant renal vein thrombosis⁸.

References

1. Eagle, K. A., P. B. Berger, et al. (2002). "ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery--executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery)" J Am Coll Cardiol 39(3): 542-553
2. Task Force Members. (2004). "Expert consensus document on beta-adrenergic receptor blockers: The Task Force on Beta-Blockers of the European Society of Cardiology." Eur Heart J; 25: 1341-1362.
3. Devereaux, P. J., W. S. Beattie, et al. (2005). "How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials" BMJ; 331(7512): 313-321
4. Lindenauer, P. K., P. Pekow, et al. (2005). "Perioperative Beta-Blocker Therapy and Mortality after Major Noncardiac Surgery" N Engl J Med; 353(4): 349-361
5. Fleisher LA, Beckman JA, et al. (2006). "ACC/AHA2006 Guideline update on perioperative cardiovascular evaluation for noncardiac surgery: focused update on perioperative beta-blocker therapy." Journal of the American College of Cardiology 47(11)
6. Mangano, D. T. and the Multicenter Study of Perioperative Ischemia Research Group (2002). "Aspirin and Mortality from Coronary Bypass Surgery" N Engl J Med; 347(17): 1309-1317
7. Auerbach, A. and L. Goldman (2006). "Assessing and Reducing the Cardiac Risk of Noncardiac Surgery" Circulation 113(10): 1361-1376
8. Robertson AJ, Nargund V, Gray DW, Morris PJ. Low dose aspirin as prophylaxis against renal-vein thrombosis in renal-transplant recipients. Nephrol Dial Transplant. 2000; 15(11):1865-8

Guideline 2.4 - Tx : Preparation of the renal transplant recipient

Patients should be strongly encouraged to stop smoking before and after transplantation. Formal smoking cessation programmes should be offered and accessed in primary care. (Good practice)

Audit measure

The proportion of patients who smoke (or have given up within the last year) a) whilst listed for transplantation b) one year after renal transplantation

Rationale

Cigarette smoking increases the risk of cancer and cardiovascular disease in the general population. Only a few studies have examined the effect of cigarette smoking on renal transplantation but all show an association with reduced patient and graft survival. In one study of patients with a functioning graft at least one year after transplantation, cigarette smoking correlated with reduced patient survival and the magnitude was quantitatively similar to that of diabetes¹. In a larger single centre North American study, smoking more than 25 pack-years at the time of transplantation (compared to smoking less than 25 pack-years or never having smoked) was associated with a 30% higher risk of graft failure after correcting for multiple known risk factors². The increase in graft failure was largely due to an increase in deaths. Stopping smoking more than 5 years before transplantation reduced the relative risk of graft failure by 34%. The relative risks of major cardiovascular disease events and invasive malignancies were significantly increased in smokers. Similar results have been observed in another study in which pre-transplant smoking was associated with reduced transplant and death-censored graft survival although death-censored graft survival was significantly higher in patients who stopped smoking before transplant evaluation³. Evidence suggests that with appropriate interventions, many patients can stop smoking^4-5.

References

1. Cosio FG, Falkenhain ME, et al. Patient survival after renal transplantation: II. The impact of smoking. Clinical Transplantation 1999; 13(4): 336-341
2. Kasiske B and K. D. Cigarette smoking in renal transplant recipients. Journal of the American Medical Association 2000; 11: 753-759
3. Sung RS, Althoen M, et al. Excess risk of renal allograft loss associated with cigarette smoking. Transplantation 2001; 71(12): 1752-1757
4. Silagy C, Mant D, et al. Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet 1994; 343: 139-142
5. Hughes JR, Goldstein MG, et al. Recent advances in the pharmacotherapy of smoking. Journal of the American Medical Association 1999; 281: 72-76

Guideline 2.5 - Tx : Preparation of the renal transplant recipient

Obese patients (BMI >30) present technical difficulties and are at increased risk of peri-operative complications. They should be screened rigorously for cardiovascular disease and each case considered individually. Although obesity is not an absolute contra-indication to transplantation, individuals with a BMI >40 kg/m² are less likely to benefit. (Good practice)

Audit measure

a). The proportion of obese patients (BMI >30) on the transplant waiting list who have had a cardiac assessment.

b). The number of patients with BMI >40 kg/m² who are on the transplant waiting list and the reason for their inclusion.

Rationale

Body mass index (BMI) is the most widely used marker of obesity despite its limitations. According to the WHO classification a BMI of 30-34.9 kg/m² is defined as obese class I (mild), 35-39.9 kg/m² as obese class II (moderate) and >40 kg/m² as obese class III (morbid). The impact of obesity on outcome after renal transplantation has been controversial. For obese patients overall, registry data has demonstrated a significant survival advantage for recipients of both deceased and living donor transplantation compared with remaining on dialysis¹. However, recipients of deceased donor transplants with a BMI >41 had no survival benefit. Some single centre studies have shown that wound infections, delayed graft function and weight gain are more common in moderately and morbidly obese transplant recipients although patient and graft survival are unchanged^2-3. In a small paired kidney analysis of 28 pairs, obesity defined as a BMI >30 was associated with decreased graft survival at 5 years⁴. In another study in which patients were rigorously screened (and excluded) for cardiovascular disease before acceptance for transplantation, 5 year patient and graft survival were no different in the obese (BMI >30) group⁵. Wound breakdown was commoner. A recent analysis of 27 377 patients from the UNOS database showed that compared with normal weight patients, a BMI >35 was independently associated with an increased risk of delayed graft function, prolonged hospitalisation, acute rejection and decreased overall graft survival although a high proportion of such individuals were African Americans and had diabetes mellitus⁶.

References

1. Glanton CW, Kao TC, et al. Impact of renal transplantation on survival in end-stage renal disease patients with elevated body mass index. Kidney International 2003; 63(2): 647-653
2. Drafts HH, Anjum MR, et al. The impact of pre-transplant obesity on renal transplant outcomes. Clinical Transplantation 1997; 11: 493-496
3. Howard RJ, Thai VB, et al. Obese kidney transplant recipients have good outcomes. Transplantation Proceedings 2001; 33: 3420-3421
4. Yamamoto S, Hanley E, et al. The impact of obesity in renal transplantation: an analysis of paired cadaver kidneys. Clinical Transplantation 2002; 16(4): 252-256
5. Johnson DW, Isbel NM, et al. The effect of obesity on renal transplant outcomes. Transplantation 2002; 74(5): 675-681
6. Gore JL, Pham PT, et al. Obesity and outcome following renal transplantation. American Journal of Transplantation 2006; 6: 357-363

Guideline 2.6 - Tx : Preparation of the renal transplant recipient

All potential transplant recipients should be tested for prior exposure to viral infections including: cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), hepatitis B and C and human immunodeficiency virus (HIV). Immunization should be offered to all hepatitis B (if not already immunized) and VZ virus antibody negative patients before transplantation. Patients otherwise suitable for renal transplantation with evidence of chronic hepatitis B and/or C or HIV infection should be managed according to British Transplantation Society and European Best Practice Guidelines prior to transplantation. (Good practice)

Audit measure

a). The proportion of patients on the transplant waiting list whose viral status is known for CMV, EBV, VZV, hepatitis B and C and HIV.

b). The proportion of VZV and HBc antibody negative patients on the transplant waiting list who have been immunized against these viruses.

Rationale

It is important to know if potential transplant recipients have had exposure to certain viruses, notably Epstein-Barr virus (EBV), cytomegalovirus(CMV) and varicella zoster(HZV). EBV negative recipients of an EBV positive transplant have a seven-fold increased risk of post-transplant lympho-proliferative disorder (PTLD)¹. Knowledge of recipient CMV serology at transplantation will be essential to guide antiviral prophylactic strategies².

Potential recipients who are hepatitis B surface antigen positive will require assessment by a hepatologist with liver biopsy if circulating viral DNA is present, before placement on the waiting list³. Active viral replication, chronic active hepatitis or cirrhosis has a poor prognosis if untreated before transplantation⁴. In hepatitis C, survival post-transplantation is increased over remaining on dialysis⁵. It is recommended that the potential transplant recipient has a liver biopsy to assess liver damage and consideration of treatment before transplantation⁶.

The advent of highly active antiviral therapy has revolutionized the prognosis of HIV, and early experience suggests similar early graft and patient survival rates between HIV -positive and negative renal transplant recipients⁷. Guidelines for the management of potential kidney transplant recipients with HIV infection should be followed.⁸

References

1. Shahinian VB, Muirhead N, Jevnikar AM et al. Epstein-Barr virus seronegativity is a risk factor for late onset post-transplant lymphoproliferative disorder in adult renal allograft recipients. Transplantation 2003; 75: 851-6
2. Newstead C, Griffiths PD, O’Grady JG, Parameshwar JK. Guidelines for the prevention and management of cytomegalovirus after solid organ transplantation. 2^nd Edition. British Transplantation Society 2004. ISBN 0-9542221-3-X
3. European Best Practice Guidelines (EBPG). Nephrol Dial Transplant 2000;15(7):9-11
4. Fornairon S, Pol S, Legendre C, Carnot F, Mamzer-Bruneel MF, Brechot C, Kreis H. The long-term virologic and pathologic impact of renal transplantation on chronic hepatitis B virus infection. Transplantation 1996; 27: 297-9
5. Pereira BJ, Natov SN, Bouthot BA, Murthy BV, Ruthazer R, Schmid CH, Levey AS. Effects of hepatitis C infection and renal transplantation on survival in end-stage renal disease. Kidney Internatl 1998; 53: 1374-81
6. European Best Practice Guidelines (EBPG). Nephrol Dial Transplant 2000;15(7):7-9
7. Abbott KC, Swanson SJ, Agodoa LY, Kimmel PL. Human immunodeficiency virus infection and kidney transplantation in the era of highly active antiretroviral therapy and modern immunosuppression. J Am Soc Nephrol 2004; 15: 1633-9
8. Guidelines for Kidney Transplantation in Patients with HIV Disease 2005 www.bts.org.uk/standards

Guideline 2.7 - Tx : Evaluation and selection of the renal transplant recipient

In potential recipients with previous malignancy (excluding non-melanoma skin cancer), renal transplantation should only be considered if there is no evidence of persistent cancer. It is recommended that the waiting time between successful tumour treatment/remission and transplantation be at least 2 years. For certain malignancies the waiting time may need to be extended to more than 5 years. The Israel Penn International Transplant Tumor Registry should be consulted for tumour specific advice (www.ipittr.uc.edu/Home.cfm). (Good practice)

Rationale

The risk of several forms of malignancy is markedly increased after transplantation¹, due in part to alteration of immune surveillance mechanisms with maintenance immunosuppression. Patients with successfully treated cancer can be considered for renal transplantation however it is important to estimate the risk of cancer relapse before placement on the transplant waiting list. Relapse of solid organ tumours is dependent upon tumour type and time interval between treatment and transplantation. Overall 53% of recurrences occurred in patients transplanted within 2 years of cancer treatment, falling to 34% if the interval between treatment and transplantation was 2-5 years and 13% if the interval was more than 5years². The risk of recurrence is very low for non-melanoma skin cancer and in-situ carcinoma of the cervix or bladder such that no delay in placement on the waiting list is required. The risk of recurrent colorectal cancer, melanoma, and breast cancer is higher and the disease-free interval may need to be at least 5 years before transplantation depending on cicumstances². Liaison with an oncologist is advised.

Although there is evidence that dialysis patients have an increased incidence of cancer over the general population³, currently there is no evidence that dialysis patients on the transplant waiting list should have increased cancer surveillance strategies over that recommended for the general population⁴. Previous post-transplant lymphoproliferative disease (PTLD) is not a contraindication to re-transplantation.

References

1. Agraharkar ML, Cinclair RD, Kuo YF, Dallar JA, Shahinian VB. Risk of malignancy with long-term immunosuppression in renal transplant recipients. Kidney Int 2004; 66: 383-
2. Penn I. The effect of immunosuppression on pre-existing cancers. Transplantation 1993; 55: 742-7
3. Maisonneuvre P, Agodoa L, Gellert R, Stewart JH et al. Cancer in patients on dialysis for end-stage renal disease: An international collaborative study. Lancet 1999; 10: 93-9
4. Kiberd BA, Keough-Ryan T, Clase CM. Screening for prostate, breast and colorectal cancer in renal transplant recipients. Am J Transplant 2003; 3: 619-25

Guideline 2.8 - Tx : Evaluation and selection of the renal transplant recipient

Patients who are at risk of developing recurrence of original renal disease should be managed according to the European Best Practice Guidelines (EBPG). Nephrol Dial Transplant 2000;15(7):11-20 (Good practice)

Rationale

Recurrent disease accounts for approximately 5% of all allograft loss¹; primary focal segmental glomerulosclerosis, IgA nephropathy, mesangio-capillary glomerulonephritis type II and diabetic nephropathy are the commonest causes. Pre-transplantation counseling should include the potential risk of recurrent disease in appropriate patients. In rare circumstances transplantation may be contraindicated because of the very high risk of recurrent disease for example in recipients who have lost their first allograft early from recurrent disease².

References

1. Chadban S. Glomerulonephritis recurrence in the renal graft. J Am Soc Nephrol. 2001; 12(2):394-402
2. European Best Practice Guidelines (EBPG). Nephrol Dial Transplant 2000; 15(7):11-20

Guideline 2.9 - Tx : Screening investigations in the renal transplant recipient

There is no evidence that asymptomatic potential transplant recipients require screening for diverticular disease, peptic ulceration or gall bladder stones.

Rationale

Colonic perforation due to diverticular disease after renal transplantation is rare with modern immunosuppressive regimes utilizing low dose corticosteroids. Furthermore, in a retrospective study in which all transplant candidates aged more than 50 years underwent screening, none of the patients with significant diverticular disease had symptomatic disease post-transplantation¹. Patients with clinically significant disease should be assessed and managed according to standard practice. Peptic ulceration is now rarely a serious problem and there is a low morbidity rate even in patients with past peptic ulcer disease². Most transplant centers ignore incidental cholelithiasis and there is no published evidence from the recent era to support a role for screening and intervention before transplantation.

References

1. McCune TR, Nylander WA, van Buren DH, Richie RE, MacDonell RC Jr, Johnson HK et al. Colonic screening prior to renal transplantation and its impact on post-transplant colonic complications Clin Transplant. 1992;6(2):91-6
2. Troppman C, Papalois BE, Chiou A, Benedetti E. Dunn DL, Matas AJ, et al. Incidence, complications, treatment, and outcome of ulcers of the upper gastrointestinal tract after renal transplantation during the cyclosporine era. J Am Coll Surg 1995;180:433-43

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ACKNOWLEDGMENTS

The above guidelines on the assessment of the potential renal transplant recipient have been endorsed by the British Transplantation Society.

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