The Effect of Recipient Age on Outcome After Pancreas Transplantation

The trend toward improved pancreas transplant (PT) outcomes in North America likely reflects more rigorous selection of recipients and donors.1 At the same time, the average age of PT recipients has increased.1 In other solid organ transplants, long-term graft survival is inferior in older recipients, but death-censored graft survival is similar.2,3 This was probably the genesis of PT recipient age restrictions in some centers, although there is no consensus regarding the appropriate age cutoff.4,5 Disease severity and comorbidity is likely a better predictor of postoperative complications than age.2 Nevertheless, older patients are less likely to be listed due to perceived risks of the procedure.2,6 Single center studies comparing results of PT recipients older than 50 years to those of younger recipients, have not found evidence of clinically significant disparity in short- or long-term outcomes;4,5,7,8 however, UNOS registry data suggest that the optimal graft survival accrues to recipients aged 40 to 49 years9 As such, 50 years appears to be the inflection point for decline in long-term PT outcomes with age. The aim of this study was to determine whether, in a large North American center, the PT outcomes differ between patients above and below the age of 55 years. All primary PTs (n=382; 286 simultaneous pancreas and kidney and 96 pancreas after kidney) performed at the Toronto General Hospital between April 1995 and April 2013 were entered into a prospective database and analyzed retrospectively. Given data showing equivalent short, intermediate, and long-term outcomes for SPK and PAK,10-12 the analysis included both PT types. Institutional recipient selection,13 immunosuppression and infection prophylaxis protocols, evaluation of graft function, assessment and treatment of rejection, short- and long-term transplant outcomes during this era and statistical analysis techniques have been described previously.10,14 Thirty recipients were 55 years or older, whereas 352 patients were younger than 55 years. Both groups of recipients had similar donor characteristics. All were classified clinically as type 1 diabetics. During the period of the study, there was a secular trend toward an increasing recipient age. The program has no upper age limit for eligibility, and the aging profile of recipients is primarily due to referral patterns. Consequently, the median follow-up of recipient aged 55 years or older was significantly shorter (32 vs. 77 months, P<0.001). A higher proportion of recipients aged 55 aged 55 years or older had cardiac intervention preoperatively (46% vs. 13%, P < 0.001). Apart from age, there were no other differences in recipient characteristics between the study groups. Notably, the period of diabetes before transplant was not different. In the first 3 months after transplantation, there was a lower rate of rejection (either pancreas or kidney) in the recipients aged 55 years or older (13% vs. 33%, P = 0.02), and a trend toward a shorter time to onset of first rejection in the recipients younger than 55 years (22.7 days vs. 47 days, P = 0.18), but this was not statistically significant. There were no other significant differences in the occurrence of other early postoperative complications (including bleeding requiring return to operating room, graft thrombosis, or graft pancreatitis). The median postoperative hospital stay was 10 days in both groups. Over a 5-year follow-up period, there was no difference in pancreas or kidney graft function. There was no difference in pancreas (Figure 1A) or kidney (Figure 1B), graft survival, or patient survival (Figure 1C). As can be seen in the survival curve, in the younger than 55 years age cohort, there were 4 graft losses in the first month after transplantation. Overall, there were 8 graft losses in this cohort. Therefore, 50% of the graft losses occurred in a time frame that could be classified as technical. In the younger than 55 years age cohort, only 16% of graft losses occurred within the first month (P = 0.03). There was only 1 death of a recipient aged 55 years or older with graft function, and so death-censored graft survival was not analyzed. There was no statistically significant difference in the frequency of graft loss from any cause between the 2 age cohorts.FIGURE 1: Kaplan-Meier survival curves illustrating (A) pancreas, (B) kidney, and (C) patient survival of PT recipients 55 years or older compared to those younger than 55 years. Graft survival is not censored for patient death. The number of subjects at risk is noted for each group for each survival curve.This study examined PT outcomes in recipients 55 years or older in a single North American center. The difference in mean age between the 2 cohorts was more than 15 years, but they had diabetes for a similar length of time (about 25 years). This suggests that although chronologically different in age, these 2 patient cohorts have reached a similar point in the evolution of the complications of their diabetes after a similar number of years of exposure.15 Significantly more of the older patients had undergone preoperative cardiovascular intervention. This suggests that achieving equivalent outcomes in an older patient group may require either excluding patients where significant cardiovascular disease is detected or prophylactic intervention to prevent consequent postoperative complications. This study is limited by its retrospective design, small number of patients in the older cohort, and the analysis of data from a single institution. The follow-up of the recipients 55 years or older is shorter as a consequence of the aging demographic of PT recipients in this centre. Significantly more patients in the older cohort suffered graft loss in the first month of transplantation; however, these data are difficult to interpret because of the small numbers of graft failures in the age younger than 55 years cohort. As a result, the long-term survival data should be interpreted with caution. Patient selection bias is an important potential confounding factor at several levels. Although pancreas transplantation is routinely offered to patients determined to be medically suitable irrespective of age, those who ultimately pursue transplantation may not be representative of the potential recipient pool as a whole. In conclusion, patients 55 years or older did not have an increased risk of postoperative complications, and there was no difference in patient or graft survival. Although intuitively, older recipient age should be associated with inferior outcomes as a result of shorter life expectancy, in this admittedly small cohort of patients, 55 years does not appear to be the inflection point for decline in PT outcomes with age.

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