how old is old for transplantation?

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  • American Journal of Transplantation 2004; 4: 20672074Blackwell Munksgaard

    Copyright C Blackwell Munksgaard 2004

    doi: 10.1111/j.1600-6143.2004.00622.x

    How Old is Old for Transplantation?

    Gabriel C. Oniscua,, Helen Brownb

    and John L. Forsythea

    aTransplant Unit, The Royal Infirmary of Edinburgh, UK andbInformation and Statistics Division, Scottish NationalHealth Service, UKCorresponding author: Gabriel C. Oniscu,gabriel@oniscu.fsnet.co.uk

    Elderly patients are the fastest growing group re-quiring renal transplantation. This study investigateswhether transplantation is worthwhile in the elderlyand whether there is evidence supporting an age limitfor transplantation.

    One thousand ninety-five adults transplanted inScotland between 1 January 1989 and 31 December1999 were followed up to 11 years. Sociodemographic,comorbidity and transplant data were obtained fromthe national databases and patients notes. Patient andgraft survival, risk and causes of graft failure and pa-tient death were compared between four age groups(1849, 5059, 6064 and >65).

    All groups had similar gender, social deprivation andrenal disease distribution. The incidence of comorbid-ity increased with age. The groups had comparableHLA matching, but patients aged 1849 years receivedtransplants from younger donors and with shorter coldischaemic times. Younger patients had more acute re-jection and less delayed graft function. Older patientshad a higher incidence of death with functioning graft.Patients over 65 years had an almost dialysis-free re-maining life, while the graft half-life was significantlyshorter than patient half-life in the youngest group.

    Transplantation in elderly recipients is worthwhile de-spite a higher comorbidity. Careful selection ratherthan a fixed age limit should be used to ensure a sat-isfactory graft and patient survival.

    Key words: Renal transplantation, elderly patients,outcome, comorbidity, survival, multivariate analysis,graft survival, clinical assessment

    Received 13 March 2004, revised and accepted for pub-lication 22 July 2004

    Introduction

    The number of elderly patients accepted in renal replace-ment programmes is continuously increasing. In Scotland,

    a country of five million people, the incidence of end stagerenal disease (ESRD) has risen dramatically from 61 permillion population (pmp) in 1990, to 109 pmp in 1999. Thepercentage of ESRD patients over 60 years has increasedfrom 42% in 1989, to 65% in 1999. In fact, patients agedover 65 years represented more than half of the total num-ber of new patients in 1999 (1). A similar trend was notedin the United States, where the number of patients over 65years requiring RRT doubled in the last decade (2), Australia(3), Japan, Canada and the rest of Europe (4).

    On the basis of evidence that transplantation is safe andsuccessful (5,6) and survival with a transplant is better thanthat on dialysis (7,8) even in older patients, there is a gen-eral consensus that age per se should not represent abarrier to transplantation. And yet, many centers are stillreluctant to accept elderly patients onto the waiting list dueto their comorbid conditions (9) and shorter life expectancy.In addition, an increased age at the time of transplantationhas a significant impact on long-term graft survival (10) anddeath with a functioning graft is a common event duringthe follow-up (11).

    Although in the United Kingdom there is no age limit foraccess to transplantation and the listing and transplanta-tion criteria are identical for all patients irrespective of theirage, only 7.2% of transplant recipients are aged over 65years (12). In the United States, where extended criteriadonors (ECD) are used increasingly in recent years, only9.9% of patients over 65 years are transplanted with non-ECD, while 22.9% receive an ECD kidney (13). In Scotland,where the UK national listing and transplantation criteria areapplied, significant inequities in access to the waiting listand renal transplantation according to patients age havebeen described (14). Only 26% of those aged 6064 yearsand respectively 8.5% of those over 65 years are on thewaiting list for transplantation within 3 years of startingRRT. After listing, only 43% of the 6064 years old pa-tients and respectively 29% of those over 65 years aretransplanted within 3 years. This is in stark contrast to over70% of patients aged 1849 years listed within 3 years ofstarting RRT. More than 60% of those listed in this agegroup received a transplant within 3 years.

    In the context of the current organ shortage, there is acontinuous debate whether elderly patients should go ontothe national waiting lists, or they should be part of speciallydesigned schemes to which older or marginal kidneys arepreferentially allocated. Currently in the United Kingdom,there are no such schemes and the selection criteria for

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  • Oniscu et al.

    the transplant waiting list and subsequent transplantationare identical for all patients irrespective of their age.

    Therefore, the aim of this paper was to compare the resultsof kidney transplantation in different age groups and toinvestigate whether transplantation is worthwhile in theelderly or we should set an age limit for access onto thewaiting list.

    Methods

    All adult patients who started dialysis between 1 January 1989 and31 December 1999 and were transplanted with a cadaveric kidney (firstgraft) until 31 December 2000 (n = 1095) were grouped according to theirage at grafting (1849 years, 5059 years, 6064 years and >65 years). Thekidneys were distributed according to the national criteria set by the UKTransplant. They are based on closeness of HLA with three tiers (tier 1 =no HLA mismatch, tier 2 = one mismatch for HLA-A and/or HLA-B and nomismatches for HLA-DR, tier 3 = one or two HLA-DR mismatches and/ortwo mismatches for HLA-A and/or HLA-B). At each level, priority is given topediatric over adult recipients, highly sensitized over non-sensitized, localversus national recipients. If more than one recipient is identified, a pointscoring mechanism is used as a discriminator based on the following crite-ria: recipient age, donor/recipient age difference, waiting time, matchability,sensitization and balance of exchange between centers. Although the al-gorithm has been revised several times throughout this study, all criteriacontinued to apply to all patients, irrespective of their age.

    The sociodemographic and extensive comorbidity data, as well as the levelof HLA matching, the length of the cold ischaemic time, patient and graft

    Table 1: Comparison of baseline characteristics of transplanted patients according to the age at transplantation

    1849 years 5059 years 6064 years >65 years(n = 686) (n = 252) (n = 82) (n = 75) p-value

    Male:Female ratio 57.9:42.1 67.5:32.5 64.6:35.4 66.7:33.3 0.033a

    Primary renal disease (%) 0.174Glomerulonephritis 28.7 30.2 23.2 34.7Interstitial nephritis 35.0 34.9 31.7 25.3Multisystem disease 11.2 13.5 17.1 18.7Diabetes 13.7 8.3 11.0 8.0Other 11.4 13.1 17.1 13.3

    Deprivation category (%) 0.621 (least deprived) 5.0 5.2 6.1 4.02 12.0 13.1 14.6 18.73 22.6 21.8 23.2 30.74 26.1 26.6 29.3 29.35 15.3 16.3 15.9 6.76 12.6 11.5 8.5 9.37 (most deprived) 6.4 5.6 2.4 1.3

    HD as 1st RRT (%) 56.5 59.9 62.2 58.6 0.785Median duration of pre-transplant dialysis (years) 1.3 1.33 1.62 1.92 0.031a,b

    Number of switches between dialysis modalities (%) 0.034a

    0 65.7 64.5 61.7 76.01 21.3 21.6 29.6 13.3>2 13.0 13.9 8.7 10.7

    Listing center (%)

  • How Old is Old for Transplantation?

    Table 2: Comparison of comorbidity characteristics of transplanted patients according to the age at transplantation

    1849 years 5059 years 6064 years >65 years p-value

    Peripheral vascular disease (%) 5.0 11.9 16.3 27.3

  • Oniscu et al.

    Patient survival following transplantation (years)

    121086420

    Cum

    ulat

    ive s

    urviv

    al1.2

    1.0

    .8

    .6

    .4

    .2

    Age groups

    >65 years

    6064 years

    5059 years

    1849 years

    Age group 1 year 3 years 5 years 8 years

    1849 5059 6064 >65

    98 92 87 91

    93 88 76 77

    91 81 59 66

    82 61 49 33

    Figure 1: Patient survival followingtransplantation (p < 0.0001, Log-ranktest).

    recipients aged >65 years, but this was compensated bya higher proportion of tier 2 (010, 010 or 110 mismatches)grafts.

    As expected, the donor age increased, the older the recip-ient, from 38 years in the younger recipients, to 48 yearsin those >65 years, but with a comparable gender distri-bution.

    Younger patients (1849 years) were transplanted within ashorter cold ischaemic time (mean 1126 min), but had ahigher incidence of acute rejection episodes, while elderlypatients (>65 years) had a higher incidence of delayed graftfunction.

    All patients had an excellent 1-year survival rate (Figure 1).There were no significant differences between the sur-vival curves in the first year post-transplantation, but asexpected, there were substantial differences in the long-term survival between those younger and those older than60 years. It was noted that up to 5 years post-transplant,those aged >65 years had a better survival than patientsaged 6064 years. At 8 years post-transplant, half of thepatients in the 6064 years old group were alive comparedwith one third in the >65 group.

    Similar differences were noted for the graft survival(Figure 2), 60% of the transplants performed in patientsyounger than 60 years functioning at 8 years, in contrastwith only 3040% in those over 60 years. However, graftsurvival in patients aged >65 years was comparable withthat seen in the 5059 years group for the first 5 yearspost-transplant. When t

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