The organ shortage is the dominant issue in kidney transplantation today. The number of patients on the United Network of Organ Sharing (UNOS) waiting list continues to increase by over 3,000 patients per year, and it is projected that over 75,000 patients will be waiting for a kidney transplant by 2010 (1). Because of the aging end-stage renal disease (ESRD) population, most of the growth in the wait-listed population has been among older patient groups. Between 1994–2003, the proportion of wait-listed patients aged ≥50 years increased from 36% to 54% while the number of new registrants aged ≥64 years increased threefold (1). The need for transplantation in younger age groups has in part been met by the expanded use of living donor transplantation. However, living donor transplantation continues to be relatively infrequent among older wait-listed ESRD patients. Elderly ESRD patients may be more likely to identify potential living donors of similar age to them, and may be reluctant to accept living donor transplantation from younger donors including their children. Increased utilization of older aged living kidney donors may be an important strategy to meet the need for transplantation, particularly among elderly ESRD patients.
Whether the relative infrequent use of living donor transplantation among older patients is due to a reluctance to utilize older living donors is unknown. The recent increased utilization of older aged deceased donors was in part the result of information demonstrating acceptable clinical outcomes with the use of these organs (2–4). In order to determine whether increased use of older living donors can also help to meet the urgent need for transplantation, we describe the incidence and outcomes of kidney transplantation as a function of living donor age.
We studied all first kidney-only transplant recipients in United States Renal Data System between April 1995 and December 2003. Donor characteristics were determined from the TXUNOS, and recipient characteristics were determined from the Medevid standard analysis files, respectively. Donor and recipient characteristics were described using the mean±standard deviation (SD) or frequencies, and group differences were compared with t test or chi-square test as appropriate.
We first determined factors associated with receipt of an older living donor transplant in a multivariate logistic regression analysis. Because more than 90% of all living donor transplants were from donors <55 years, we chose donor age ≥55 years to define an older living donor in this logistic regression model.
We then determined the association of living donor age with the outcomes of graft survival, and allograft function (glomerular filtration rate one year after transplantation estimated using the four variable equation derived from the Modification of Diet in Renal Disease study) (5). For the purposes of comparison, the analyses of transplant outcomes included both deceased and living donor transplant recipients. Graft survival was determined from the date of transplantation until death, return to dialysis, or end of study (December 2004). The time to graft loss (including death) was determined using the Kaplan-Meier product limit method and group differences were compared with the log rank test. The independent association of living donor age with graft survival was determined using a Cox multivariate regression model that included adjustment for other factors that were associated with graft survival (P<0.05) in univariate analyses. All analyses were performed SAS version 9.1. Local university hospital ethics board approval was obtained prior to initiating this study.
There were 73,073 patients studied including 31,255 living donor recipients, and 41,745 deceased donor recipients (73 patients had missing donor information and were excluded). The mean±SD recipient age was 47±13 years. The majority of the recipients were male (60%), of white race (74% white, 20% black, 6% other race), had nondiabetic ESRD disease (cause of ESRD was diabetes in 31%, glomerular disease in 28%, and due to other causes in 42%), and had no history of cardiovascular disease (history of ischemic heart disease, congestive heart failure, peripheral vascular disease, stroke present in 7%, 9%, 4%, and 2%, respectively).
Table 1 shows the characteristics of living donor transplant recipients by donor age. The majority of patients (90%) received transplants from living donors <55 years of age, and there were only 64 recipients of living donor transplants from donors ≥70 years. The estimated pretransplant GFR was lower among older-aged donors. There was no evidence of increased transplantation from older living donors during the study period 1995–2003 (P=0.22).
Factors Associated with Receipt of Living Donor Transplant from a Donor ≥55 Years
The odds of receiving a living donor transplant from a donor ≥55 years were higher among recipients of older age, female gender, white race, preemptive transplants, and spousal donor transplants (Table 2). Compared to the reference group of blood relatives, the odds of receiving a living donor transplant from a donor ≥55 years was greater when the donor was the husband (odds ratio 4.2, 95% CI: 3.5–5.0) rather than the wife (odds ratio 1.96, 95% CI: 1.7–2. 3) of the recipient (P<0.001 for the interaction of gender×spousal donor source). Cause of ESRD, waiting time, employment status, and type of medical coverage were not associated with receipt of a living donor transplant from a donor ≥55 years.
Outcomes: Allograft Function One Year after Transplantation
The estimated mean±SD GFR one year after transplantation in recipients of living donor transplants from donors aged <55, 55–59, 60–64, 65–69, and ≥70 years was 56.2±18.2, 47.2±14.9, 45.9±15.9, 42.2±15.5, and 41.4+15.8 ml/min/1.73 m2, respectively. In comparison, recipients of deceased donor transplants from donors aged <55 years and ≥55 years was 57.1±20.8 and 41.6±16.8 ml/min/1.73 m2, respectively.
Outcomes: Allograft Survival
Graft survival among recipients of living donor transplants from donors ≥55 years was 85% and 76% at three and five years respectively. In comparison, graft survival at three and five years among living donor recipients from donors <55 years was 89% and 82%, while that of deceased donor recipients from donors <55 years was 82% and 73%. The survival of living donor recipients from donors <70 years was superior or comparable to that of recipients of deceased donor transplants from donors <55 years (Fig. 1). The survival of the few (n=64) living donor recipients from living donors ≥70 years appeared similar to that from deceased donors ≥55 years (Fig. 1).
Table 3 shows the results of two separate Cox multivariate regression analyses to determine the association of living donor age with allograft survival. Model 1 shows the relative risk of graft loss compared to the reference group of deceased donor transplant recipients from donors aged <55 years. Recipients of living donor transplants from donors aged 55–64 years and 65–69 years had the same relative of risk of graft loss as the reference group, while recipients from living donors aged 65–69 (HR=1.3, 95% CI: 1.1–1.7) and >70 years (HR=1.7, 95% CI: 1.1–2.6) had a higher relative risk of graft loss. Model 2 shows that compared to the reference group of recipients of living donor transplants from donors aged <55 years, transplant recipients from living donors aged 55–64, 65–69, and ≥70 years had a progressively higher risk of graft loss. Similar results were obtained in both models when death was excluded as a cause of graft loss (data not shown). We found no evidence that graft survival among recipients of older living donor transplants was effected by recipient age (interaction of donor and recipient age was nonsignificant in both models).
Our findings demonstrate that excellent clinical outcomes are achieved with transplantation from older living kidney donors up to the age of 65 years. Graft survival from living donors aged 55–59 years and 60–64 years was similar to that from deceased donors aged <55 years. Although the risk of graft failure was clearly related to living donor age, the five-year graft survival from living donors ≥55 years was still 76%. Living donor graft survival was decreased with donor age ≥65 years and there were few transplants performed from living donors ≥70 years. Despite these excellent outcomes, only 10% of all living donors were ≥55 years and there was no increase in the frequency of transplantation from older aged living donors during the study period. Although older recipients were more likely to receive transplants from older aged living donors, only 17% of living donor recipients ≥55 years received transplants from a donor ≥55 years.
Our findings extend the observations from single center studies demonstrating acceptable outcomes from older aged living donors by identifying a cut-point of 65 years beyond which the survival of living donor transplants is significantly decreased (6–10). We found no interaction between living donor age and recipient age, suggesting that transplantation from living donors up to the age 65 years may be considered for all adult recipients. Importantly the GFR achieved 12 months after transplantation was lower among recipients of older living donor transplants. Our analysis did not consider factors such as recipient size, which may be an important consideration in deciding whether to proceed with transplantation from an older aged living donor.
We found that living donor recipients of older age, white race, female gender, preemptive transplants, and spousal donor transplants had a higher odds of transplantation from a donor aged ≥55 years. We also found higher odds of older living donor transplantation with male spousal donors. These observations differ from previous studies demonstrating that females are more likely to donate rather than to receive a living donor transplant (11–13). It is possible that these differences may in part be due to “size selection” of older aged, but larger male living donors for smaller female recipients in an effort to maximize allograft function after transplantation. Our findings suggest that increased utilization of older aged living donors may be an effective strategy to increase preemptive transplantation particularly among older recipients who have decreased survival on dialysis.
When interpreting our findings, readers should consider the inherent limitations of observational studies using administrative data sets. In addition, we do not have complete information regarding donor characteristics including predonation glomerular filtration rate, and donor size that may influence the decision to proceed with living donor transplantation from an older donor. Similarly, we do not have information regarding donor outcomes after nephrectomy, and there is limited information regarding the outcomes of elderly living donors (14). Further studies of donor outcome are needed to understand the implications of expanded use of older living kidney donors.
In summary, we found excellent graft survival with living donors up to the age of 65 years. Recipients of transplants from living donors aged ≥65 years were at increased risk of graft loss compared to recipients of transplants from deceased donor aged <55 years. Transplantation from living donors ≥55 years of age is infrequent and not increasing over time. Older recipients, preemptive transplant recipients, and recipients of spousal donor transplants were more likely to receive transplants from donors ≥55 years of age. In contrast to previous studies of living donor transplantation, transplantation from living donors ≥55 years was more likely among female recipients, and when the spouse was the husband of the recipient. Increased utilization of living donors up the age of 65 years may be an important strategy to help meet the urgent demand for transplantation.
Dr. Gill is Scholar of The Michael Smith Foundation for Health Research. The data were supplied by the United States Renal Data System. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the U.S. government.
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