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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2013  |  Volume : 24  |  Issue : 4  |  Page : 673-681
Impact of donor age on outcome of kidney transplantation from controlled donation after cardiac death


South West Transplant Centre, Gastroenterology, Surgery and Renal Services Directorate, Plymouth Hospitals NHS Trust, Derriford Hospital, Plymouth PL6 8DH, United Kingdom

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Date of Web Publication24-Jun-2013
 

   Abstract 

Previous reports regarding donation after cardiac death (DCD) have called for caution in extending the age of kidney donors beyond 60 years due to the risk of poor graft function. The aim of this study was to determine the impact of donor age on renal transplantation from DCD in one center. All DCD transplants from 2005 to 2009 were included in the study. Immunosuppression and recipient follow-up were as per unit protocol. Donor and recipient details were entered prospectively into a renal database and analyzed for graft outcome. Of the 147 renal transplants, 102 were from donors <60 years old and 45 were from donors ≥60 years old. The incidence of delayed graft function varied significantly according to donor-recipient age groups (P = 0.01). The mean glomerular filtration rate at 12 months was 50.3 mL/min for transplants from young donors compared with 39.3 mL/min for transplants from old donors (P = 0.001). The cumulative graft survival rates at 1 and 5 years were 88% and 79% for young donors, while for old donors these were 78% and 72%, respectively (P = 0.101). By transplanting kidneys from old DCD donors into elderly patients, their survival is improved compared with dialysis, and organs from younger donors are made available for younger recipients.

How to cite this article:
Akoh JA, Rana TA. Impact of donor age on outcome of kidney transplantation from controlled donation after cardiac death. Saudi J Kidney Dis Transpl 2013;24:673-81

How to cite this URL:
Akoh JA, Rana TA. Impact of donor age on outcome of kidney transplantation from controlled donation after cardiac death. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Oct 20];24:673-81. Available from: http://www.sjkdt.org/text.asp?2013/24/4/673/113846

   Introduction Top


The persistent increase in demand for renal transplantation and the inadequacy of various programs to substantially increase the number of organs has advanced the debate from whether to use organs from donors after cardiac death (DCD) to what type of DCD organs are not suitable for transplantation. In response to this protracted shortage, organs from extended criteria donors (ECD), including donors with a history of hypertension or diabetes mellitus, are being used with increasing frequency. [1] The percentage of recovered kidneys that are discarded has increased from 10% in 1998 to 17% in 2007, which is most likely due to the increasing use of ECD and DCD donors. [2]

Previous reports regarding DCD have called for caution in extending the age of kidney donors beyond 60 years due to the associated risks of lower glomerular filtration rate and reduced allograft survival. [3],[4] However, there is no consensus on the upper age limit for DCDs.

The overriding concern when using DCD kidneys from older donors is whether the donated nephron mass is sufficient to produce adequate function for the recipient. Many factors including donor disease/co-morbidity, cold ischemia time (CIT) and recipient variables affect the short- and long-term graft outcomes. Whereas younger recipients achieved acceptable 5-year graft survival despite donor hypertension, ischemic heart disease or a combination of both, these factors significantly reduced graft survival in older recipients; [5] about 21% of kidney failures resulted from insufficient nephron mass due to advanced age. [6] However, in a review of a large registry data, the marginal renal transplantation was associated with a substantial reduction in mortality and improvement in life expectancy when compared with candidates who remained on dialysis. [7] Recently, a panel of international pathologists recommended a biopsy-based scoring system to aid the decision making process regarding the use of kidneys from donors over 60 years. [8]

The current study was undertaken to determine the impact of donor age on transplantation from controlled DCD and explore how to maximize the use of marginal DCD organs.


   Patients and Methods Top


All renal transplants from controlled DCD donors (Maastricht category 3) [9] from 2005 to 2009 were included in the study. Non-heart beating donors (now referred to as DCD) are grouped by the Maastricht classification into: I - brought in dead; II - unsuccessful resuscitation; III - awaiting cardiac arrest; IV - cardiac arrest after brain stem death; and V - cardiac arrest in a hospital inpatient. Recipient selection was based on an agreed local allocation policy [best Human Leucocyte Antigen (HLA) match, donor-recipient age difference ≤20 years, low matching scores, e.g. ethnic minorities, long waiting times and health status] effected by the National Health Service Blood and Transplant (NHSBT).

Immunosuppression comprised basiliximab (induction), tacrolimus (0.1 mg/kg/day), mycophenolic acid (2 g/day) and prednisolone. The follow-up after recipient discharge was according to the routine practice in the unit.

Transplant biopsies were performed in patients with delayed graft function (DGF, defined as requirement for dialysis within the first week of transplantation) or transplant dysfunction. If DGF persisted beyond seven days, repeat biopsies were performed weekly until there was demonstrable fall in serum creatinine (Cr). Histological assessment evaluated the presence and severity of interstitial fibrosis, vessel disease (atherosclerosis), glomerular sclerosis and acute rejection and whether there were features compatible with acute tubular necrosis. Acute rejection was treated with high-dose pulsed Methylprednisolone. Primary nonfunction (PNF) was defined as a graft that never worked until its removal or that never allowed the recipient to come off dialysis.


   Statistical Analysis Top


Donor age, cause of death, body mass index (BMI), Cr, urine output during the last surviving hour and co-morbidities, along with recipient details [age, primary disease, rejection, Cr level, estimated glomerular filtration rate (eGFR) and complications] were entered prospectively into a renal computer database (Proton® Information System, Clinical Computing, plc, London) and Microsoft Excel. eGFR was calculated using the modification of diet in renal disease (MDRD) formula. Data were entered into an especially designed proforma and analyzed using SPSS 16 for Windows (SPSS Inc, Chicago, IL, USA). HLA mismatch, cold ischemia time (CIT), early and late graft function, time to halving of serum Cr level and Cr at 3, 6 and 12 months were compared for transplants from donors aged <60 years and ≥60 years during the period of the study.

A more detailed analysis of transplant parameters according to donor-recipient age group pairings (donor <60 years to recipient <60 years; donor <60 years to recipient ≥60 years; donor ≥60 years to recipient <60 years; donor ≥60 years to recipient ≥60 years) was also performed. Age <60 years was regarded as young and ≥60 years as old for the purpose of comparison. Differences between groups were tested by the x 2 statistic, with a P-value <0.05 considered as significant. Also, differences in the rates of DGF, incidence of biopsy-proven acute rejection (BPAR) and the mean graft survival between donor types were evaluated by the F or x 2 statistical tests. The differences between the mean CIT, HLA mismatches and time to halving serum Cr were analyzed by the one-sample t-test. Overall graft survival according to donor age groups and survival according to donor-recipient age groups were constructed using Kaplan-Meier estimates (IBM SPSS Statistics 19, SPSS Inc.). The log-rank test was used to assess for equality of survival distributions among groups.


   Results Top


During the period of study, there were 147 renal transplants from DCD donors ranging in age from 11 years to 76 years (mean ± SEM 49.1 ± 1.27 years; median 52 years). The recipients of the organs were slightly older, with an age range of 22-75 years, a mean of 54.84 ± 0.91 years and a median of 55 years. There were 102 (69.4%) transplants from young donors (median 47 years) and 45 (30.6%) transplants from old donors (median 65). Whereas the difference in the mean BMI, CIT, Cr, urine output during the last hour before donation and time to halving recipient's Cr after transplantation from donors <60 years and those ≥60 years did not reach statistical significance, there were significant differences in terms of other outcome parameters, as shown in [Table 1].
Table 1: Transplant parameters according to donor age group.

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The cause of death of donors was undetermined in 22 cases (11 donors). Intracranial hemorrhage accounted for 47/125 (38%) donor kidneys, followed by hypoxic brain injury in 39/125 (31%) and head trauma in 23/125 (18%). When the three most common causes of donor death accounting for 111 (76%) of cases were analyzed separately for influence on DGF or graft loss, there were no statistically significant differences found (Pearson x 2 = 7.553; DF = 4; P = 0.109). Hypertension (17%) and diabetes (12%) were the most common co-morbidities among the donors. Twenty-four percent (11/45) of the old donors were hypertensive compared with 14% (14/102) of the young donors - the difference was not statistically significant (Yates x 2 = 1.839, P = 0.175). However, 91% (41/45) of the old donors and 75.5% (77/102) of the young donors had one or more co-morbidities and the difference was statistically significant (Yates x 2 = 3.875, P = 0.049).

The majority (91.2%) of the recipients underwent their first renal transplantation, while only 11 (7.5%) and two (1.4%) recipients received their second and third transplants.

Five patients underwent early graft nephrectomy (during the first week) due to renal vein thrombosis in four and arterial occlusion in one. Arterial occlusion occurred in a graft from an old donor who was discovered to have abdominal aortic aneurysm during organ recovery. The sister graft was discarded due to severe renal arterial disease and poor perfusion of the kidney. The incidence of PNF was 6.7% (3/45) in transplants from older donors compared with 2.9% (3/102) for younger donors. All three cases of PNF in the older donor group were due to non-recovering acute tubular necrosis whereas in the younger donor group, one was due to thrombotic microangiopathy, another due to refractory vascular rejection and the third due to acute tubular necrosis. The incidence of DGF was 43/96 (45%) for kidneys retrieved from donors <60 years old and 22/40 (55%) for kidneys from donors ≥60 year old (Yates x 2 = 0.806; P = 0.369). Similarly, the age of the recipient did not significantly influence the rate of DGF (x 2 = 6.253; DF = 3; P = 0.10). However, the incidence of DGF varied significantly according to donor-recipient age groups [Table 2].
Table 2: Analysis of transplant parameters according to donor and recipient age group matchings.

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Fifty-eight (57%) of the 102 recipients of kidneys from younger donors required biopsies compared with 30 of the 45 (67%) donors in the older donor group. The old donor group also had a higher repeat biopsy rate - 72% compared with 44% in the young donor group. There were no statistically significant differences in the distribution and severity of fibrosis between donor age groups (Pearson x 2 = 2.615; DF = 2; P = 0.264; Yates x 2 = 1.868; P = 0.392). Forty of the 58 (69%) recipients of kidneys from the young donor group who had biopsies displayed donor vessel disease compared with 21 of 30 (70%) in the old group [Table 3], but this was not statistically significant (Pearson x 2 = 5.570; DF = 3; P = 0.135; Yates x 2 = 3.908; P = 0.271). However, the incidence of moderate to severe donor vessel disease of 34.5% in the young group, when compared with 56.6% in the older group, was found to be statistically significant (Pearson x 2] = 3.993; DF = 1; P = 0.045).
Table 3: Distribution of atherosclerosis in donor organs according to donor age groups.

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The number of HLA mismatches on the three major loci ranged from zero to six in two recipients, with 61 recipients having three mismatches. The distribution of HLA mismatches was not statistically significantly different according to donor age group (Yates x 2 = 3.728; P = 0.713). The old donor to young recipient had the lowest mean mismatch, but the differences between the donor-recipient age group pairings were not statistically significant [Table 2]. Mismatches on the DR-loci were also not significantly different between the groups. Neither the donor nor the recipient age group significantly influenced the overall incidence of BPAR (Yates x 2 = 1.502; P = 0.681 and Yates x 2 = 1.882; P = 0.597, respectively). However, a more detailed analysis revealed that the rejection rate was the highest when an old donor kidney was transplanted into a young recipient [Table 2], which was statistically significant (Pearson x 2 = 8.128; DF = 3; P = 0.04).

Recipients of DCD kidneys were followed-up from one to 63 months after transplantation, with a mean of 23.4 ± 1.44 months. At the end of the follow-up period, six recipients died with functioning grafts, of which five deaths were due to unrelated causes and one from post-transplant lymphoproliferative disorder. Sixteen allografts failed for various reasons [six PNF and five early and five late graft failures). The overall cumulative survival probability for all grafts at 1 and 5 years was 85% and 76%, respectively, with a mean survival of 50.9 ± 2.06 months (95% CI 46.9-54.9)]. The cumulative graft survival probability at 1 year (5 years) were 88% and 78% for young and old donor kidneys, respectively, (log rank (x 2 ) = 2.682; DF = 1; P = 0.101; [Figure 1]). However, there was a statistically significant difference in survival distribution between the donor-recipient groups (log rank (x2 ) = 8.061; DF = 3; P = 0.045; [Figure 2]).
Figure 1. Cumulative survival distribution of kidney transplants following donation after cardiac death according to donor age groups.

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Figure 2. Cumulative graft survival distribution according to donor–recipient age groups.

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   Discussion Top


Earlier reports indicated that allografts from older donors were associated with inferior function, suboptimal graft survival [3] and a higher discard rate, [4] and recommended restricted use. However, the lack of improvement in organ supply due to the decreased availability of DBD organs coupled with the successful outcome of our local DCD program necessitated a re-examination of the criteria for accepting DCD organs for transplantation. Our experience is similar to that reported by Wells and co-workers, [10] who, in the initial phase of their DCD program, did not select donors over 60 years but later expanded their criteria to bring it in line with DBD donors. This study shows that a significant proportion (30%) of DCD kidneys used were from donors over 60 years of age. This is higher than the figures reported from elsewhere in the UK. [5],[11]

Although the overall graft outcome was satisfactory, there were significant differences in outcome between grafts from young and old donors [Table 1] even though both groups outcome between grafts from young and old donors [Table 1] even though both groups were well matched in terms of BMI, CIT, urine output during the last hour and number of HLA mismatches. This finding is broadly comparable with previous reports of donation after brain stem death renal transplants that a younger donor age is associated with a better outcome. [6],[12],[13] This study shows that kidneys from donors over 60 years (a quarter of whom were hypertensive) are more likely to exhibit significant atherosclerosis and, consequently, a higher degree of graft dysfunction. Based on the experience of Fraser et al, [5] these old DCD grafts would perform better in young recipients. However, in this series, the acute rejection rate in younger recipients of old DCD kidneys was significantly higher than the other categories, in spite of a better HLA mismatch profile. In contrast, the finding in the European Senior Program (ESP) that acute rejection was more common in the old to old group, [14] reflected the increased immunogenicity of older grafts. [15]

[Figure 2] shows that most of the graft losses in the recipients of kidneys from old donors occurred early. This is in agreement with an earlier report that most of the deleterious effects of receiving a kidney from an older donor occurred within one year. [12] It is thought that DGF initiates a programmed process in the graft, which may result in chronic changes. [16],[17] However, Cooper and co-workers [18] reported that the long-term outcomes of DBD and DCD were equivalent, despite a higher rate of DGF in the latter.

An important limitation of this study is that time zero biopsies were not routinely performed in spite of the fact that 91% of the donors 60 years or older had one or more comorbid factor(s). As biopsies were performed only on clinical grounds, there might be a selection bias. Nevertheless, it is reasonable to conclude that kidneys from older donors are more likely to have chronic disease. In an earlier series where biopsies were performed prior to implantation, undue reliance might have been placed on the percentage of glomerular sclerosis in deciding whether to use the organ or not. [19] The value of using the severity of glomerulosclerosis in predicting graft outcome is controversial. [20],[21],[22],[23],[24],[25] Remuzzi et al [26] showed that using pre-implantation biopsies in influencing kidney allocation was the only independent factor predicting improved long-term graft survival. The scoring system allocated equal weight to glomerular sclerosis, tubular atrophy, interstitial fibrosis and vessel disease. [8] Given the increased likelihood of co-morbidities in the older donors, we recommend time zero allograft biopsies when transplanting DCD kidneys from donors over 60 years.

There is no agreement regarding the benefits of age matching of donor grafts and recipients. This is perhaps due to the different standards used in judging the "success" of a transplant in an elderly versus a young recipient. Another factor responsible for this is the fact that graft or patient survival does not necessarily correlate with the quality of graft function. The ESP [14] demonstrated that patient survival was better when younger donor organs were implanted into older recipients. Also, older kidneys have a better graft survival when transplanted into older recipients. [27] Older to younger transplants were associated with the poorest graft survival outcomes. [28] Our study shows that considering BPAR, DGF and eGFR at 12 months [Table 2], donor and recipient age matching would produce best results in young to young; good results in old to old; less good results in young to old; and fair results in old donors to young recipients. Our results are similar to the findings of Kwon and co-workers [29] even though they used age 50 years as the cutoff point between young and old.

The proposal to utilize kidneys from older donors in older recipients remains controversial. [12],[15],[30] In using DCD kidneys from older donors, there is a need to balance the likelihood of senescence, loss of nephron mass, reduced graft survival, increased risk of interstitial fibrosis, tubular atrophy, poor immediate function, progressive graft dysfunction and higher impact of acute rejection on graft function in balance with the benefits of the recipients, including removal from dialysis. Given the worsening trend in organ supply, the ever-increasing elderly population on transplant waiting lists with a shorter life expectancy, the higher death rate in the elderly while waiting for a transplant and using DCD kidneys from over 60-year-old donors for the elderly would seem a pragmatic step. Experience with the ESP showed a doubling of the proportion of transplant kidneys from donors over 65 years of age with the old to old policy. [14]

Recipients of renal transplantation from old DCD donors exhibit inferior function and are likely to require more frequent biopsies and follow-up clinical visits compared with those receiving grafts from young donors. In spite of the foregoing and a slightly higher risk of DGF, DCD kidneys from older donors exhibit similar long-term survival to younger donors and are therefore a valuable resource. The use of elderly DCD kidneys for older patients on the waiting lists offers a win situation. By transplanting and therefore removing elderly patients from the waiting list and dialysis, their survival is improved (compared with those remaining on dialysis) and organs from younger donors are made available for younger recipients.


   Limitations of the Study Top


Failure to perform time zero biopsies on all donor kidneys.

A relatively short follow-up (mean 23 months), given the delayed impact of DGF on graft survival.

Conflict of interests: None

 
   References Top

1.Perico N, Ruggenenti P, Scalamogna M, Remuzzi G. Tackling the shortage of donor kidneys: How to use the best that we have. Am J Nephrol 2003;23:245-59.  Back to cited text no. 1
    
2.2008 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1998-2007. U.S. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation, Rockville, MD. Available from: http://optn.transplant.hrsa.gov/ar2008/Preface_C ontributors.htm?cp=1). [Last accessed on 2010 August 04].  Back to cited text no. 2
    
3.Snoeijs MG, Schaefer S, Christiaans MH, et al. Kidney transplantation using elderly non-heart-beating donors: A single-center experience. Am J Transplant 2006;6:1066-71.  Back to cited text no. 3
    
4.Akoh JA, Denton MD, Bradshaw SB, Rana TA, Walker MB. Early results of a controlled non-heart-beating kidney donor programme. Nephrol Dial Transplant 2009;24:1992-6.  Back to cited text no. 4
    
5.Fraser SM, Rajasundaram R, Aldouri A, et al. Acceptable outcome after kidney transplantation using "expanded criteria donor" grafts. Transplantation 2010;89:88-96.  Back to cited text no. 5
    
6.Terasaki PI, Gjertson DW, Cecka JM, Takemoto S, Cho YW. Significance of the donor age effect on kidney transplants. Clin Transplant 1997;11:366-72.  Back to cited text no. 6
    
7.Ojo AO, Hanson JA, Meier-Kriesche H, et al. 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.  Back to cited text no. 7
    
8.Remuzzi G, Grinyò J, Ruggenenti P, et al. 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.  Back to cited text no. 8
    
9.Kootstra G, Daemen JH, Oomen AP. Categories of non-heart-beating donors. Transplant Proc 1995;27:2893-4.  Back to cited text no. 9
    
10.Wells AC, Rushworth L, Thiru S, et al. Donor kidney disease and transplant outcome for kidneys donated after cardiac death. Br J Surg 2009;96:299-304.  Back to cited text no. 10
    
11.Rudge C. Long-term patient and graft survival in the eurotransplant senior program: A single-center experience. Transplantation 2005;80: 571-2.  Back to cited text no. 11
    
12.Basar H, Soran A, Shapiro R, et al. Renal transplantation in recipients over the age of 60: The impact of donor age. Transplantation 1999;67:1191-3.  Back to cited text no. 12
    
13.Vianello A, Mastrosimone S, Calconi G, et al. Influence of donor age on cadaver kidney graft function and survival: Univariate and multi-variate analyses. Nephron 1993;65:541-8.  Back to cited text no. 13
    
14.Frei U, Noeldeke J, Machold-Fabrizii V, et al. Prospective age-matching in elderly kidney transplant recipients--a 5-year analysis of the Eurotransplant Senior Program. Am J Transplant 2008;8:50-7.  Back to cited text no. 14
    
15.Denecke C, Habichtb A, Chandraker A, Tullius SG. The impact of donor age and recipient age on clinical course and immune response after organ transplantation. Transplant Rev 2006; 20:179-88.  Back to cited text no. 15
    
16.Tilney NL, Guttmann RD. Effects of initial ischemia/reperfusion injury on the transplanted kidney. Transplantation 1997;64:945-7.  Back to cited text no. 16
    
17.Boom H, Mallat MJ, de Fijter JW, Zwinderman AH, Paul LC. Delayed graft function influences renal function, but not survival. Kidney Int 2000;58:859-66.  Back to cited text no. 17
    
18.Cooper JT, Chin LT, Krieger NR, et al. Donation after cardiac death: The University of Wisconsin experience with renal transplantation. Am J Transplant 2004;4:1490-4.  Back to cited text no. 18
    
19.Gaber LW, Moore LW, Alloway RR, Amiri MH, Vera SR, Gaber AO. Glomerulosclerosis as a determinant of posttransplant function of older donor renal allografts. Transplantation 1995;60:334-9.  Back to cited text no. 19
    
20.Cockfield SM, Moore RB, Todd G, Solez K, Gourishankar S. The prognostic utility of deceased donor implantation biopsy in determining function and graft survival after kidney transplantation. Transplantation 2010;89:559-66.  Back to cited text no. 20
    
21.Escofet X, Osman H, Griffiths DF, Woydag S, Adam Jurewicz W. The presence of glomerular sclerosis at time zero has a significant impact on function after cadaveric renal transplantation. Transplantation 2003;75:344-6.  Back to cited text no. 21
    
22.Randhawa PS, Minervini MI, Lombardero M, et al. Biopsy of marginal donor kidneys: Correlation of histologic findings with graft dysfunction. Transplantation 2000;69:1352-7.  Back to cited text no. 22
    
23.Lu AD, Desai D, Myers BD, Dafoe DC, Alfrey EJ. Severe glomerular sclerosis is not associated with poor outcome after kidney transplantation. Am J Surg 2000;180:470-4.  Back to cited text no. 23
    
24.Edwards EB, Posner MP, Maluf DG, Kauffman HM. Reasons for non-use of recovered kidneys: The effect of donor glomerulosclerosis and creatinine clearance on graft survival. Transplantation 2004;77:1411-5.  Back to cited text no. 24
    
25.Sung RS, Christensen LL, Leichtman AB, et al. Determinants of discard of expanded criteria donor kidneys: Impact of biopsy and machine perfusion. Am J Transplant 2008;8: 783-92.  Back to cited text no. 25
    
26.Remuzzi G, Cravedi P, Perna A, et al. Dual Kidney Transplant Group. Long-term outcome of renal transplantation from older donors. N Engl J Med 2006;354:343-52.  Back to cited text no. 26
    
27.Hariharan S, McBride MA, Bennett LE, Cohen EP. Risk factors for renal allograft survival from older cadaver donors. Transplantation 1997;64:1748-54.  Back to cited text no. 27
    
28.Waiser J, Schreiber M, Budde K, et al. Age-matching in renal transplantation. Nephrol Dial Transplant 2000;15:696-700.  Back to cited text no. 28
    
29.Kwon OJ, Lee HG, Kwak JY. The impact of donor and recipient age on the outcome of kidney transplantation. Transplant Proc 2004; 36:2043-5.  Back to cited text no. 29
    
30.Meier-Kriesche HU, Cibrik DM, Ojo AO, et al. Interaction between donor and recipient age in determining the risk of chronic renal allograft failure. J Am Geriatr Soc 2002;50:14-7.  Back to cited text no. 30
    

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Correspondence Address:
Jacob A Akoh
Consultant General and Transplant Surgeon, Level 04, Derriford Hospital, Plymouth PL6 8DH
United Kingdom
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DOI: 10.4103/1319-2442.113846

PMID: 23816713

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