Are some kidneys better than others? Clinical goals and the challenging ethical landscape

Abstract

The increasing shortage of donor kidneys available for transplantation combined with an ageing population has resulted in the use of expanded-criteria donor (ECD) kidneys. These kidneys are associated with an increased risk of delayed graft function, acute rejection and reduced graft survival. This paper will cover the use of ECDs and the presentation of risk to patients receiving these organs.

Introduction

Renal transplantation remains the treatment of choice in patients with end-stage renal disease (ESRD), which not only improves the quality of life but also significantly reduces long-term mortality.^1–3 In 2010, 7183 patients in the UK were awaiting a kidney transplant, with 2694 transplants performed the previous year (2009–2010).⁴ Approximately, 25% of these patients will be transplanted within the first year, and five years after being listed on the national kidney transplant waiting list 63% will have received a transplant. The median time on the waiting list for a kidney transplant in the UK is 1088 days.⁴ Similar trends have been reported in the USA and in Western Europe.^5–7

Marginal/expanded-criteria donors

The increasing gap between demand for and supply of organs for transplants has resulted in the expansion of the deceased donor kidney pool to include those organs which previously may have been deemed unsuitable. This gap can be explained by a reduction of deaths from road traffic accidents (as a result of safer driving and better safety features in new cars), a reduction in cerebrovascular accidents and improved outcomes from neurosurgical and intensive care units.⁸

Kauffman et al. ⁹ coined the term ‘expanded-criteria donors’ (ECDs) in 1997 to describe those kidneys transplanted that did not meet the criteria for standard donor kidneys. These ECDs, also known as ‘marginal’ donors, are those over 60 years of age or older than 50 years with two of the following three criteria: previous history of hypertension, serum creatinine greater than 132 µmol/L and/or cerebrovascular cause of death.¹⁰ These four donor characteristics are significantly and independently associated with an increased risk of failure of deceased donor kidney transplants (relative risk [RR] 1.7).¹⁰

Outcomes in ECD transplantation

ECD kidneys are associated with worse outcomes than standard criteria donor kidneys (SCD), which have traditionally come from deceased donors between the ages of 10 and 39 years, with death not resulting from a cerebrovascular cause, with no history of hypertension and with a serum creatinine of less than 132 µmol/L (normal range 80–120 µmol/L). ECD post-transplant outcomes include increased risk of primary non-function (PNF), delayed graft function (DGF) and lower graft survival when compared with SCDs.^11–17 Patient survival is similar in the short term, but in the longer term (> 5 years) is lower in those patients who receive ECD kidneys.^15,18–20 The majority of single- and multicentre reports demonstrate a worse 1–15-year patient and graft outcome using ECD kidneys compared with SCD kidneys.^2,10,21–43

Is ECD kidney transplantation better than dialysis?

In spite of these poorer outcomes, mortality is lower with an ECD kidney transplant compared with a patient undergoing dialysis.² Ojo et al. ² showed that the average increase in life-expectancy for a recipient of an ECD kidney compared with those in the waiting list dialysis cohort was five years. The amount of time spent on dialysis also increases patient risk of death.⁴⁴ Subgroup analysis demonstrated significant survival improvement in those patients over 40 years of age, non-Hispanics, diabetics, unsensitized patients with hypertension and those on the waiting list for more than four years.

Older donors and older recipients: the era of the elderly

One in 10 of the world's population is over 60 years of age. It is anticipated that this will rise to one in five by the year 2050.⁴⁵ Even the elderly population is ageing, with those over 80 years being the fastest-growing subgroup. The incidence of chronic diseases (including cardiovascular disease, hypertension, diabetes and ESRD) increases with age.⁴⁶ Older patients (i.e. >60 years) represent the fastest-growing group of patients with ESRD, resulting in an increased number of older patients on the transplant waiting list.^41,47,48 In 2008, US Renal Data System showed that the number of patients over 60 years of age with ESRD was 237,293 (those under 60 years of age with ESRD numbered 268,962).

In the years from 2002 to 2006, the number of patients over 60 years of age with ESRD on the transplant waiting list was less than 5% and 10%, respectively.⁴⁹ Ojo et al. ² showed that elderly patients on the waiting list have a higher mortality than younger patients. A patient over 65 years of age on the waiting list for five years has a 50% chance of dying before receiving a transplant. Elderly patients continue to derive a survival benefit from kidney transplantation if they undergo transplantation within three years.^50,51 The median waiting time for an SCD transplant in the USA for a patient over 65 years of age is approximately four years.⁵²

Living donation in the elderly

Comparison of outcomes of transplantation in the elderly from old living donors (OLDs), i.e. donors aged over 55 years, young living donors (YLDs), SCDs and ECDs have demonstrated superior allograft and patient survival in OLDs compared with SCD and ECD transplants.⁵³ Recipients of OLD transplants had reduced PNF (patients whose grafts have never functioned), DGF (the need for one or more haemodialysis treatments following transplantation prior to the onset of graft function) and acute rejection compared with ECD grafts. Transplants from YLDs remain the optimal choice. Gill et al. ⁵³ demonstrated that transplants from OLDs up to the age of 64 years had increased graft and patient survival compared with deceased donations after cardiac death. Recipients of transplants from OLDs over 65 years of age also had better allograft survival compared with those from ECDs. This study highlights that living donor transplantation from donors over 65 years of age may be an alternative for older recipients, particularly where transplantation using an ECD may be the only available option.

In living donation, the majority of donors are siblings and spouses.⁵⁴ Should we be considering older donors? Are older recipients more likely to accept an organ from an older or younger donor? A survey of the 132 transplant centres in the USA found that 21% of programmes excluded donors over 65 years of age.⁵⁵ Studies have shown that the life-expectancy of kidney donors is similar to that of non-donors; however, there have been reports of kidney donors themselves subsequently being placed on waiting lists for transplantation.^56–58 While there is no reported increase in ESRD in kidney donors, increases in serum creatinine can be prolonged.^59–63 The retrospective review of 3698 kidney donors from Minneapolis (1963–2007) by Ibrahim et al. ⁶⁴ revealed no difference in survival of donors and subsequent development of ESRD compared with age- and sex-matched controls. This study confirmed the view that risk factors for reduction in glomerular filtration rate (GFR, a marker of overall kidney function) are the same as for the general population – age and increased weight. It is important for centres to quantify the risk associated with donor nephrectomy and to ensure that this information is available to potential donors so that they can decide whether these risks are acceptable.

Allocation programmes for older patients

The Eurotransplant Senior Programme (ESP), started in 1999, was developed to improve the efficiency of use of kidneys from older donors.^65,66 The ESP matches donors with recipients of a similar age group, disregarding human leukocyte antigen (HLA) (tissue type) matching, with kidneys allocated to local recipients to reduce cold ischaemia time. Three-year follow-up has shown no difference in graft survival comparing kidneys from older donors (ESP) with those from the usual HLA allocation system (non-ESP). Analysis of data from 70,000 deceased kidney transplants performed between 1988 and 1998 demonstrated a greater effect of donor age than recipient age on graft survival.³⁴

A decision analysis model by Jassal et al. ⁶⁷ determining the costs and benefits of kidney transplantation versus haemodialysis in older patients, demonstrated a significant increased overall life-expectancy and quality-of-life improvement at a reasonable cost in the transplanted group. Prolonged waiting times, however, significantly reduce the clinical benefits and economic benefit of transplantation in this group.

Evaluation of older kidney transplant patients is costly.⁶⁸ The process should provide adequate information so that the recipient can make an informed decision about their care. Older kidney transplant patients will have to make a difficult decision between receiving a kidney transplant (either living donor, ECD or SCD) and remaining on dialysis. Patients must be informed that even if they are placed on the waiting list, their medical condition could deteriorate and may result in them being removed from it.⁶⁹ Potential kidney recipients are evaluated as soon as they are referred to the transplant clinic. Social and psychological evaluation of the candidate is important to evaluate how they will care for themselves post-transplant. It is important to address the patients' expectations prior to the transplant ensuring that they are realistic.

Do surgical retrieval teams make kidneys marginal?

Damage to kidneys during the organ-retrieval process is an increasing problem, which is under-reported. Data from the NHS BT database on deceased donor kidney retrievals over a five-year period demonstrated damage in 19% (1726 of 9014) of kidney retrievals.⁷⁰ Only 96 (1% of the total retrieved) were unsuitable for transplantation because of damage. Confirmation of damage between the retrieval and recipient teams was only noted in 3% of cases. Damage to kidneys was increasingly reported in organs retrieved from kidney-only donors (26%) rather than those retrieved by a multiorgan team (21%). The lowest risk of damage occurred when a high-output (>50 retrievals) liver team retrieved both liver and kidney (17%). Interestingly, the frequency of kidney injury increased with donor age, especially those over 39 years of age. Similar data were reported in a 10-year retrospective analysis from a single-centre study in Germany, reporting injury in 21% (103 of 486) of retrieved kidneys, of which 3.7%¹⁸ were rejected due to poor organ procurement.⁷¹ The German Medical Association currently requires a surgical trainee to be supervised retrieving 10 cases, before proficiency is achieved.

Can you calculate risk?

The definition of ECD kidneys assumes that all transplanted organs have the same risk of graft loss (i.e. >1.7); however, the reported risk of graft loss for ECD has been variable (1.74–2.69).¹⁰ An index was developed using all significant donor risk factors: donor race and age, donor/recipient cytomegalovirus match, cause of death, HLA (tissue type) match, cold ischaemia time (in surgery, the time between the chilling of a tissue, organ or body part after its blood supply has been reduced or cut off and the time it is warmed by having its blood supply restored), and donor history of diabetes and hypertension.⁷² In order to better evaluate the variability in ECD kidneys, a model was developed for recipients transplanted from 1995 to 2002.⁷³

A cumulative risk assessment score was generated in patients with significant donor risk factors (including donor age, race, HLA matching, cause of death and history of hypertension): 33% of ECD kidneys were characterized as low risk, 60% as moderate risk and 7% as high risk, with five-year overall graft survival rates of 59, 49 and 40%, respectively. Using the low-risk group as a reference level of 1.0, the multivariate RR of graft loss in the study cohort, adjusted for recipient factors, was 1.4 for the moderate-risk group and 1.9 for the high-risk group. Increased donor age is the most important variable when defining an ECD, and stroke as a cause of death and longstanding arterial hypertension are associated with poorer graft survival.^{2,21,33,74,75}

Kidneys from older donors are more susceptible to ischaemia–reperfusion injury^A and DGF – which in turn increases the risk of acute rejection and reduced graft survival.^24,26,76 Older kidneys have reduced nephron mass, further affected by ischaemia and immunosuppressive medication. The remaining glomeruli undergo hyperfiltration to maintain GFR. A prospective, matched cohort study confirmed that kidneys from older donors (i.e. 60 years), allocated to dual-kidney transplantation (a pair of kidneys with limited function transplanted into a single patient) according to a pretransplant biopsy histological score, demonstrated similar short- and medium-term outcomes to single-kidney transplants from younger donors.^77,78 Use of pretransplant biopsy increases cold ischaemia time and is expensive and the use of wedge biopsy remains uncertain.⁷⁹

Nyberg et al. ⁸⁰ studied the records of over 34,000 patients who received a cadaveric kidney between 1994 and 1995. Based on this, a donor scoring system was devised in which there are five donor variables, all of which were highly significant by univariate and multivariate analysis. A total of 39 points were distributed, with a maximum number of points per variable: age of the donor (25 points), history of hypertension (4 points), donor creatinine clearance (4 points), HLA mismatch (3 points) and cause of death (3 points). On the basis of total score, a grade was assigned to each kidney: A (0–9 points), B (10–19 points), C (20–29 points) and D (30–39 points). The donor score had a significant (P < 0.001) influence on graft survival after six years, with survival of grade A and grade B kidneys approximately 80%; in contrast, six-year graft survival was <70% for both grade C and grade D kidneys. This supports a cut-off of >20 points for definition of a marginal organ. Subgroup analysis of older (>60 years) and younger (<60 years) recipients supports a cut-off of >20 points. Six-year survival was 80.2% (<20 points, <60 years) versus 68.8% (>20 points, <60 years); 81.5% (<20 points, 60 years) versus 69.5% (>20 points, >60 years).The difference in graft survival in younger and older recipients of non-marginal kidneys was significant: 80.2% versus 81.5%. Interestingly, no difference was noted in the comparison of graft survival between older and younger recipients of marginal kidneys.

Baskin-Bey et al. ⁸¹ studied >36,000 transplant recipients and developed a recipient risk score (RRS) based on diabetes mellitus, interaction between age and diabetes, time on dialysis therapy and history of angina. Transplant recipients are stratified into four groups, RG1–RG4, with decreasing median survival from RG1 to RG4. This RRS could be combined with the DDS (deceased donor score) to optimize the allocation process. It has been predicted from this model that a 15% increase in renal supply and may in time reduce the kidney transplantation waiting list. This model will allocate more SCD kidneys to younger patients and ECD kidneys to older patients.

Balance of donor and recipient risk

One must consider three concepts in the process of deceased donor organ allocation: equity, efficiency and utility:⁸² (1) equity – all those listed for a transplant have equal opportunity; (2) efficiency (process) – ensures minimal waste of organs; and (3) utility – distribution of organs maximizes benefit to recipients, ‘the greatest good for the most people’. It has been suggested that equity and efficacy are the opposition between an individual rights and the rights of the collectives. Some have preferred a utilitarian approach for allocating deceased donor organs.⁸³ These underlying guiding theoretical principles have prompted changes in the UK deceased donor kidney allocation scheme. It was, for instance, identified that an allocation scheme that relied heavily on HLA matching disadvantaged ethnic minority groups, principally because of their under-representation in the donor pool and over-representation on the kidney transplant waiting list. Changes in the UK deceased donor allocation scheme to favour waiting time on the transplant list have to some extent addressed this issue but have also had the unintended consequence of discriminating against older patients.⁸⁴ This was not the goal, just as HLA-matching was not intended to discriminate against ethnic minorities. Life-expectancy for older transplant patients is shorter than that of younger patients, and the ‘gain of years’ compared with remaining on dialysis is less. Furthermore, exclusion from kidney transplantation as a result of age is not fair and selection should be based on biological and not chronological age.⁴⁷

With the expansion to use ECD kidneys and the willingness to operate on increasingly marginal recipients, the transplant community need to consider in terms of the marginal transplant, rather than the marginal donor/recipient. Four potential scenarios present themselves in deceased-donor renal transplantation: SCD and low-risk recipient; SCD and high-risk recipient; ECD and low-risk recipient; and ECD and high-risk recipient.

In the first scenario, a low-risk recipient receives a kidney from a SCD – this is an ideal situation. It is likely that this transplant will result in an optimum outcome and maximum use from the donor kidney in this particular patient.

In the second scenario, a high-risk recipient receives a kidney from an an ideal donor. In this case, renal function is considered wasted when kidneys with a long lifespan are allocated to recipients with short life-expectancies.⁸⁵ This results in a ‘premature death with a functioning graft’.⁸² When a patient dies with a functioning transplant, is this considered a failure or a success? Would use of the kidney have been optimised in a patient with a more favourable outcome, as this premature death increases the shortage of organs?

In the third scenario, an ECD kidney is given to a low-risk recipient. In this case, a graft with a relatively short lifespan is allocated to a patient with a long life-expectancy. Subsequent graft loss will result in the recipient being placed back on dialysis, sensitized and further listing on the transplant waiting list. Currently, 16–20% of patients are awaiting re-transplantation as a result of graft failure.^5,78,86 The waiting time for patients previously transplanted is increased as a result of presentization. A 13.8% re-transplantation rate is reported by the United Network of Organ Sharing (UNOS) data, and a large number of patients with graft failure will never receive a second transplant.

In the fourth and final scenario, an ECD kidney is allocated to a high-risk recipient. This situation disadvantages older- and higher-risk patients who will be at greater risk of primary graft non-function, decreased graft function and survival. Primary graft non-function, however, can be addressed by the use of machine organ preservation and shortened cold ischaemia times.^87,88

By utilizing 20 years of data from the Scientific Registry of Transplant Recipients and a statistical model determining kidney outcome and allocation Kidney − Pancreas Simulated Allocation Model, the number of years that a kidney transplant would add to a patient's life compared with dialysis – known as the life-years from transplant (LYFT) – can be calculated. LYFT = estimated survival after transplant minus estimated survival on dialysis × 0.8. The years on dialysis are reduced as these are less valued than a year free of dialysis.⁸⁹ Wolfe et al. ⁸⁹ calculated that by prioritizing candidates with higher LYFT scores for each kidney, more than 10,000 extra years of life could be provided each year. LYFT is a measure of utility, and its place in the allocation policy is not yet defined. Concerns are that the LYFT discriminates against the old, similarly as other matching algorithms.

A policy of young kidneys for young recipients and old kidneys for older recipients challenges equity and clearly discriminates against older patients. We must also be careful about relying on mathematical models to match patients, as there is no one-size-fits-all answer. All allocation systems must be legitimate, with people observing that the system is just and fair. Allocations must also be publicly understandable, accessible, and subject to open and frank public discussion and revision.

Presentation of risk

Patients should be informed of the risk of their operation when the decision has been made to proceed with the transplantation, i.e. at listing. Transplant recipients should be informed of the potential risks of accepting an ECD kidney prior to their operation as the decision to accept a marginal organ is complex. Recipients have the right to receive and understand all the necessary information regarding the risks and benefits to themselves and be informed of alternative treatment options. The patient's suitability for transplantation requires regular assessment as their medical condition can deteriorate and the risk of the procedure may outweigh the benefit.

Patients' choice in kidney transplantation

There are few data on patient perspectives on organ allocation. The only notable study of 128 transplant recipients and 104 dialysis patients selected which two hypothetical patients should receive a cadaveric kidney based on eight scenarios.⁹⁰ Patients in this study disagreed with several aspects of current allocation systems. The numerous current transplant allocation algorithms do not factor in individual preferences, and recipients feel that they are given little information on donor characteristics. While some recipients may be happy to receive an ECD kidney and therefore reduce the time spent on the waiting list, other recipients may want to hold out for an organ with more favourable characteristics (e.g. better HLA matching from a younger donor). Empowering patients allows the burden of responsibility in deciding whether an ECD kidney transplant may be appropriate for each particular patient to be shared.

In order to incorporate patient choice in an allocation system, Su et al. ⁹¹ developed a system in which patients will declare which range of kidneys will be acceptable for transplantation – called the UNOS/CHOICE. This system would ensure that organs will only be offered to candidates willing to accept them, and is proposed as an extension to the UNOS/ECD policy. There are disadvantages with this system, notably a significant increase in the complexity of the kidney allocation process, which may be difficult for some transplantation candidates to comprehend. The integration of donor advocates in the living donor process in transplant centres enables a non-biased professional to represent the patients' interests, and should be available when transplant physicians discuss transplant options with potential candidates.^92,93

Conclusion

In this paper, we have explained the use of ECD kidneys and associated outcomes, as well as the presentation and calculation of risk to patients with the use of these organs.

Changes in UK deceased donor allocation policy aiming to improve the use of organs may affect equity of access. The interpretation of equity may vary considerably between patients with ESRD and health-care professionals. Involving recipient choice in organ transplantation would improve outcomes relative to current allocation policies. Gains achieved by incorporating patient choice will outweigh the concerns of more complex algorithms and in time may lead to the development of a more equitable allocation policy.

Footnotes

A

Ischaemia–reperfusion injury: Ischaemia is a state of tissue oxygen deprivation accompanied by a reduced washout of the resulting metabolites. Reperfusion is the restoration of blood flow to the ischaemic tissue. Reperfusion injury is well known to cause organ damage in the brain, heart, lungs, liver, kidneys and skeletal muscle.

References

Wolfe

, Ashby

, Milford

, 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;341:1725–30

Ojo

, Hanson

, Meier-Kriesche

, Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates. J Am Soc Nephrol 2001;12:589–97

Evans

, Manninen

, Garrison

Jr , The quality of life of patients with end-stage renal disease. N Engl J Med 1985;312:553–9

Transplant

. Transplant Activity in the UK: Activity Report 2009/10. London: NHS Blood and Transplant, 2010

Gaston

, Danovitch

, Adams

, The report of a national conference on the wait list for kidney transplantation. Am J Transplant 2003;3:775–85

Eurotransplant. 2010. See http://www.eurotransplant.org/cms/mediaobject.php?file=ar_2010.pdf (last checked 29 June 2011)

Network USOPaT. 2009. See http://optn.transplant.hrsa.gov/ar2009/ (last checked 29 June 2011)

Kauffman

, Bennett

, McBride

, Ellison

. The expanded donor. Transplant Rev 1997;11:165–90

10.

Port

, Bragg-Gresham

, Metzger

, Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors. Transplantation 2002;74:1281–6

11.

Whiting

. Clinical and economic outcomes of the use of expanded criteria donors in renal transplantation. Semin Dial 2000;13:316–9

12.

Vivas

, Hickey

, Jordan

, Renal transplantation in patients 65 years old or older. J Urol 1992;147:990–3

13.

Mascaretti

, Pappalettera

, Gravame

, Chiecca

, Scalamogna

, Sirchia

. Cadaver kidney transplantation using donors with hypertension in the North Italy Transplant program. Transplant Proc 1990;22:382

14.

Lee

, Scandling

, Shen

, Salvatierra

, Dafoe

, Alfrey

. The kidneys that nobody wanted: support for the utilization of expanded criteria donors. Transplantation 1996;62:1832–41

15.

Golconda

, Whiting

, Smith

, Hayes

, Alexander

, First

. Long-term outcome of kidney transplantation from expanded criteria donors: a single center experience. Transplant Proc 1997;29:3379–81

16.

Stratta

, Rohr

, Sundberg

, Increased kidney transplantation utilizing expanded criteria deceased organ donors with results comparable to standard criteria donor transplant. Ann Surg 2004;239:688–95; discussion 95–7

17.

Dahmane

, Audard

, Hiesse

, Retrospective follow-up of transplantation of kidneys from ‘marginal’ donors. Kidney Int 2006;69:546–52

18.

Keitel

, Michelon

, dos Santos

, Renal transplants using expanded cadaver donor criteria. Ann Transplant 2004;9:23–4

19.

Lee

, Carter

, Weinstein

, Dual kidney transplantation: older donors for older recipients. J Am Coll Surg 1999;189:82–91; discussion 2

20.

Tan

, Alfrey

, Dafoe

, Millan

, Scandling

. Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up. Transplantation 2004;78:692–6

21.

Matas

, Gillingham

, Payne

Should I accept this kidney?

Clin Transplant 2000;14:90–5

22.

Cosio

, Henry

, Pesavento

, Ferguson

, Kim

, Lemeshow

. The relationship between donor age and cadaveric renal allograft survival is modified by the recipient's blood pressure. Am J Transplant 2003;3:340–7

23.

Foley

, Patton

, Meier-Kriesche

, Long-term outcomes of kidney transplantation in recipients 60 years of age and older at the University of Florida. Clin Transpl 2005:101–9

24.

Moreso

, Seron

, Gil-Vernet

, Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients. Nephrol Dial Transplant 1999;14:930–5

25.

Waiser

, Schreiber

, Budde

, Age-matching in renal transplantation. Nephrol Dial Transplant 2000;15:696–700

26.

de Fijter

, Mallat

, Doxiadis

, Increased immunogenicity and cause of graft loss of old donor kidneys. J Am Soc Nephrol 2001;12:1538–46

27.

Loven

, Norden

, Nyberg

. Impact of cadaveric renal donor morbidity on long-term graft function. Transpl Int 2003;16:857–60

28.

Fabrizii

, Winkelmayer

, Klauser

Patient and graft survival in older kidney transplant recipients: does age matter?

J Am Soc Nephrol 2004;15:1052–60

29.

Bertoni

, Rosati

, Zanazzi

, Excellent outcome of renal transplantation using single old kidneys in old recipients. Ann Transplant 2004;9:25–6

30.

Foss

, Tuvin

, Leivestad

, Oyen

, Bentdal

. Should kidneys from older cadaveric donors be age-matched to the recipient? Transplant Proc 2005;37:3280–2

31.

Messa

, Brezzi

, Cresseri

, Immediate graft function positively affects long-term outcome of renal allografts from older but not from younger donors. Transplant Proc 2006;38:3377–81

32.

Cicciarelli

, Iwaki

, Mendez

. The influence of donor age on kidney graft survival in the 1990s. Clin Transpl 1999:335–40

33.

Carter

, Lee

, Weinstein

, Lu

, Dafoe

, Alfrey

. Evaluation of the older cadaveric kidney donor: the impact of donor hypertension and creatinine clearance on graft performance and survival. Transplantation 2000;70:765–71

34.

Kasiske

, Snyder

. Matching older kidneys with older patients does not improve allograft survival. J Am Soc Nephrol 2002;13:1067–72

35.

Meier-Kriesche

, Cibrik

, Ojo

, Interaction between donor and recipient age in determining the risk of chronic renal allograft failure. J Am Geriatr Soc 2002;50:14–7

36.

Cecka

. The UNOS Renal Transplant Registry. Clin Transpl 2002:1–20

37.

Mandal

, Snyder

, Gilbertson

, Collins

, Silkensen

. Does cadaveric donor renal transplantation ever provide better outcomes than live-donor renal transplantation? Transplantation 2003;75:494–500

38.

Schnitzler

, Whiting

, Brennan

, The expanded criteria donor dilemma in cadaveric renal transplantation. Transplantation 2003;75:1940–5

39.

Keith

, Demattos

, Golconda

, Prather

, Norman

. Effect of donor recipient age match on survival after first deceased donor renal transplantation. J Am Soc Nephrol 2004;15:1086–91

40.

Gjertson

. Explainable variation in renal transplant outcomes: a comparison of standard and expanded criteria donors. Clin Transpl 2004:303–14

41.

Cecka

. The OPTN/UNOS Renal Transplant Registry. Clin Transpl 2005:1–16

42.

Merion

, Ashby

, Wolfe

, Deceased-donor characteristics and the survival benefit of kidney transplantation. JAMA 2005;294:2726–33

43.

Oppenheimer

, Aljama

, Asensio Peinado

, Bustamante Bustamante

, Crespo Albiach

, Guirado Perich

. The impact of donor age on the results of renal transplantation. Nephrol Dial Transplant 2004;19(Suppl 3):iii11–5

44.

Danovitch

, Cohen

, Weir

, Current status of kidney and pancreas transplantation in the United States, 1994–2003. Am J Transplant 2005;5(Part 2):904–15

45.

United Nations Programme on Aging. United Nations; 2010; See http://www.un.org/ageing/popageing.html (last checked 26 June 2011)

46.

Hansberry

, Whittier

, Krause

. The elderly patient with chronic kidney disease. Adv Chronic Kidney Dis 2005;12:71–7

47.

Danovitch

, Savransky

. Challenges in the counseling and management of older kidney transplant candidates. Am J Kidney Dis 2006;47(Suppl 2):S86–97

48.

Oniscu

, Brown

, Forsythe

. How great is the survival advantage of transplantation over dialysis in elderly patients? Nephrol Dial Transplant 2004;19:945–51

49.

US Renal Data System. In: Health NIo, ed. USRDS 2008 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, 2008

50.

Meier-Kriesche

, Kaplan

. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis. Transplantation 2002;74:1377–81

51.

Gill

, Tonelli

, Johnson

, Kiberd

, Landsberg

, Pereira

. The impact of waiting time and comorbid conditions on the survival benefit of kidney transplantation. Kidney Int 2005;68:2345–51

52.

OPTN: Waiting List by Organs as of January 18th 2010. 2010. See http://optn.transplant.hrsa.gov/ar2009/502_age_ki.htm (last checked 18 January 2010)

53.

Gill

, Bunnapradist

, Danovitch

, Gjertson

, Gill

, Cecka

. Outcomes of kidney transplantation from older living donors to older recipients. Am J Kidney Dis 2008;52:541–52

54.

BT N. 2010 [29.06.2011]; See http://www.organdonation.nhs.uk/ukt/how_to_become_a_donor/living_kidney_donation/living_kidney_donation.jsp (last checked 29 June 2011)

55.

Mandelbrot

, Pavlakis

, Danovitch

, The medical evaluation of living kidney donors: a survey of US transplant centers. Am J Transplant 2007;7:2333–43

56.

Fehrman-Ekholm

, Elinder

, Stenbeck

, Tyden

, Groth

. Kidney donors live longer. Transplantation 1997;64:976–8

57.

Ellison

, McBride

, Taranto

, Delmonico

, Kauffman

. Living kidney donors in need of kidney transplants: a report from the organ procurement and transplantation network. Transplantation 2002;74:1349–51

58.

Gibney

, King

, Maluf

, Garg

, Parikh

. Living kidney donors requiring transplantation: focus on African Americans. Transplantation 2007;84:647–9

59.

Fehrman-Ekholm

, Norden

, Lennerling

, Living kidney donors developing end-stage renal disease. Transplant Proc 2006;38:2642–3

60.

Bay

, Hebert

. The living donor in kidney transplantation. Ann Intern Med 1987;106:719–27

61.

Najarian

, Chavers

, McHugh

, Matas

. 20 years or more of follow-up of living kidney donors. Lancet 1992;340:807–10

62.

Ramcharan

, Matas

. Long-term (20–37 years) follow-up of living kidney donors. Am J Transplant 2002;2:959–64

63.

Ibrahim

, Rogers

, Tello

, Matas

. The performance of three serum creatinine-based formulas in estimating GFR in former kidney donors. Am J Transplant 2006;6:1479–85

64.

Ibrahim

, Foley

, Tan

, Long-term consequences of kidney donation. N Engl J Med 2009;360:459–69

65.

Cohen

, Smits

, Haase

, Persijn

, Vanrenterghem

, Frei

. Expanding the donor pool to increase renal transplantation. Nephrol Dial Transplant 2005;20:34–41

66.

Schlieper

, Ivens

, Voiculescu

, Luther

, Sandmann

, Grabensee

. Eurotransplant Senior Program ‘old for old’: results from 10 patients. Clin Transplant 2001;15:100–5

67.

Jassal

, Krahn

, Naglie

, Kidney transplantation in the elderly: a decision analysis. J Am Soc Nephrol 2003;14:187–96

68.

Kasiske

, Cangro

, Hariharan

, The evaluation of renal transplantation candidates: clinical practice guidelines. Am J Transplant 2001;1(Suppl 2):3–95

69.

Danovitch

, Cecka

. Allocation of deceased donor kidneys: past, present, and future. Am J Kidney Dis 2003;42:882–90

70.

Wigmore

, Seeney

, Pleass

, Praseedom

, Forsythe

. Kidney damage during organ retrieval: data from UK National Transplant Database. Kidney Advisory Group. Lancet 1999;354:1143–6

71.

Bentas

, Probst

, Jones

, [Quality of kidney procurement in Germany. Ten years experience and 486 renal allografts in a single centre]. Urologe A 2007;46:268–70, 71–3

72.

Schold

, Kaplan

, Baliga

, Meier-Kriesche

. The broad spectrum of quality in deceased donor kidneys. Am J Transplant 2005;5(Part 1):757–65

73.

Meier-Kriesche

H-U

, Cole

, Schold

, Patton

, Howard

, Kaplan

. Analysis of the expanded criteria donor kidneys: How good is your ECD going to be? Am J Transplant 2004;4(Supp 8):305

74.

Johnston

, O'Kelly

, Spencer

, The impact of donor spontaneous intracranial haemorrhage vs. other donors on long-term renal graft and patient survival. Clin Transplant 2006;20:91–5

75.

Pessione

, Cohen

, Durand

, Multivariate analysis of donor risk factors for graft survival in kidney transplantation. Transplantation 2003;75:361–7

76.

Lee

, Carter

, Randall

, The effect of age and prolonged cold ischemia times on the national allocation of cadaveric renal allografts. J Surg Res 2000;91:83–8

77.

Remuzzi

, Grinyo

, Ruggenenti

, Early experience with dual kidney transplantation in adults using expanded donor criteria. Double Kidney Transplant Group (DKG) . J Am Soc Nephrol 1999;10:2591–8

78.

Remuzzi

, Cravedi

, Perna

, Long-term outcome of renal transplantation from older donors. N Engl J Med 2006;354:343–52

79.

Muruve

, Steinbecker

, Luger

. Are wedge biopsies of cadaveric kidneys obtained at procurement reliable? Transplantation 2000;69:2384–8

80.

Nyberg

, Matas

, Kremers

, Improved scoring system to assess adult donors for cadaver renal transplantation. Am J Transplant 2003;3:715–21

81.

Baskin-Bey

, Kremers

, Nyberg

. A recipient risk score for deceased donor renal allocation. Am J Kidney Dis 2007;49:284–93

82.

Baskin-Bey

, Nyberg

. Matching graft to recipient by predicted survival: can this be an acceptable strategy to improve utilization of deceased donor kidneys? Transplant Rev (Orlando) 2008;22:167–70

83.

Braun

. Every kidney counts. N Engl J Med 1992;327:883–5

84.

Danovitch

, Cohen

, Smits

. Waiting time or wasted time? The case for using time on dialysis to determine waiting time in the allocation of cadaveric kidneys. Am J Transplant 2002;2:891–3

85.

Baskin-Bey

, Kremers

, Nyberg

. Improving utilization of deceased donor kidneys by matching recipient and graft survival. Transplantation 2006;82:10–4

86.

USRDS. OPTN/SRTR 2008 Annual Report. Kidney Characteristics. 2010

87.

Jochmans

, Moers

, Smits

, Machine perfusion versus cold storage for the preservation of kidneys donated after cardiac death: a multicenter, randomized, controlled trial. Ann Surg 2010;252:756–64

88.

Moers

, Smits

, Maathuis

, Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med 2009;360:7–19

89.

Wolfe

, McCullough

, Schaubel

, Calculating life years from transplant (LYFT): methods for kidney and kidney-pancreas candidates. Am J Transplant 2008;8(Part 2):997–1011

90.

Geddes

, Rodger

, Smith

, Ganai

. Allocation of deceased donor kidneys for transplantation: opinions of patients with CKD. Am J Kidney Dis 2005;46:949–56

91.

, Zenios

, Chertow

. Incorporating recipient choice in kidney transplantation. J Am Soc Nephrol 2004;15:1656–63

92.

Rudow

. The living donor advocate: a team approach to educate, evaluate, and manage donors across the continuum. Prog Transplant 2009;19:64–70

93.

Rudow

, Brown

Jr . Role of the independent donor advocacy team in ethical decision making. Prog Transplant 2005;15:298–302