Transplant recipients are predicted to have a survival advantage compared with those remaining on dialysis, and kidney transplantation is considered the treatment of choice for most patients with end-stage renal disease (ESRD) (1 1
In the past decade, the number of candidates 80 years and older awaiting a deceased donor transplant has increased 10-fold in the United States (2
RESULTS
Baseline Characteristics
Table 1 describes the baseline characteristics of the study population. There was a total of 31,179 kidney transplant recipients included in the study. Of these, 24,877 recipients were aged 60 to 69 years, 6103 were 70 to 79 years, and 199 were 80 years and older. An increased proportion of transplants in all three age categories were performed during the latter part of the study period from 2006 to 2008, but transplant recipients 80 years and older were more likely to be transplanted from 2006 to 2008 than those aged 60 to 69 and 70 to 79 years.
TABLE 1:
Baseline recipient characteristics differed among the study groups. The majority in the 80 years and older group were men (82.9%) and whites (87.9%). Recipients 80 years and older were more likely to have hypertension and less likely to have diabetes as a cause of ESRD than those aged 60 to 69 and 70 to 79 years. Comorbidities of coronary artery disease and diabetes were less frequently reported among those 80 years and older compared with the younger two age groups. There were no differences in the frequency of patients reported to have peripheral vascular disease and cerebrovascular disease, although the overall number of patients with these comorbidities was low across all age groups.
There were more expanded criteria donor (ECD) and fewer living donor transplants in the 80 years and older group compared with those aged 60 to 69 and 70 to 79 years. As such, median donor age was higher for recipients 80 years and older compared with those aged 60 to 69 and 70 to 79 years. There was no difference in the frequency of donor after cardiac death kidneys utilized in all three age groups.
Among elderly recipients, there was no difference in induction therapy use between those aged 60 to 69, 70 to 79, and 80 years and older. With respect to maintenance immunosuppression, a greater proportion of those aged 80 years and older were discharged on tacrolimus-containing regimens and fewer on mycophenolic acid or steroids compared with the younger age categories.
Early Complications
Table 2 describes graft outcomes during the initial hospitalization and at 1 year after transplant. There was a trend toward more primary nonfunction in the 70 to 79 years age group category, although the overall rate of primary nonfunction was low and differences did not reach statistical significance. Roughly one quarter of deceased donor transplant recipients in all age group categories had delayed graft function (DGF), defined as the need for dialysis within the first transplant week, and there were no differences in the rate of DGF between the three age group categories. There was no difference in the rate of acute rejection episodes during the initial hospitalization or at 1 year. Although the median length of initial hospitalization was statistically higher for recipients 80 years and older compared with those aged 60 to 69 and 70 to 79 years, this difference was only 1 day (7 days for ≥80 vs. 6 days for 60–69 and 70–79 years; P <0.001).
TABLE 2:
Patient Survival
Kaplan-Meier patient survival curves of kidney recipients aged 60 to 69, 70 to 79, and 80 years and older are shown in Figure 1(a) . There was a trend toward increased mortality among recipients 80 years and older compared with those aged 60 to 69 years during the perioperative period, defined as the first 30 posttransplant days (hazard ratio [HR] 1.67; 95% confidence interval [CI] 0.69–4.05); however, the overall rate of deaths occurring during the perioperative period was low (60–69 years: 1.4%; 70–79 years: 1.5%; and ≥80 years: 2.5%). A difference in the risk for mortality was not observed until 105 days after transplant (HR 1.83; 95% CI 1.03–3.25).
FIGURE 1.:
Unadjusted (a) patient survival, (b) graft survival, and (c) death-censored graft survival of kidney transplant recipients according to age category.
A Cox proportional hazards model was performed to adjust for recipient, donor, and transplant factors associated with patient death during the entire study period (Table 3 ). After adjusting for these factors, recipient aged 70 to 79 years had a HR of 1.42 (95% CI 1.34–1.51) and those aged 80 years and older had a HR of 2.42 (95% CI 1.91–3.06) compared with the reference group of recipients aged 60 to 69 years.
TABLE 3:
There was no difference in the risk for mortality between induction therapy and no induction among recipients 80 years and older. Compared with no induction, thymoglobulin had a HR of 0.75 (95% CI 0.35–1.62), interleukin (IL)-2 receptor antagonists a HR of 0.82 (95% CI 0.40–1.69), and alemtuzumab a HR of 0.82 (95% CI 0.28–2.47).
The causes of death reported to OPTN/UNOS are classified into 10 categories, which include cardiovascular, cerebrovascular, infection, malignancy, graft failure, hemorrhage, trauma, miscellaneous (which includes diabetes mellitus, pancreatitis, renal failure, respiratory failure, intraoperative death, suicide, noncompliance, liver failure, multisystem organ failure, and fluid/electrolyte disorders), unknown, and other. The top three causes of death among transplant recipients 60 years and older were cardiovascular (23.8%), infection (20.2%), and unknown (16.9%). Among recipients 80 years and older, the major causes of death were classified as other (28.9%), cardiovascular (22.2%), infection (22.2%), and unknown (13.3%). There were no differences in the proportion of cardiovascular (P =0.64), infectious (P =0.47), malignant (P =0.27), or cerebrovascular causes of death (P =0.89) among recipients aged 60 to 69, 70 to 79, and 80 years and older.
Graft Survival
Figure 1(b and c) show Kaplan-Meier survival curves for graft and death-censored graft survival among recipients aged 60 to 69, 70 to 79, and 80 years and older. With follow-up to 2 years, there was decreased graft survival among recipients aged 70 to 79 and 80 years and older (P <0.0001 for 70—79 vs. 60–69 and ≥80 vs. 60–69 years). Two-year graft survival was 85% for 60 to 69 years, 81% for 70 to 79 years, and 69% for 80 years and older. After censoring for patient death, 2-year death-censored graft survival was 93% for those aged 60 to 69 years, 92% for 70 to 79 years, and 91% for 80 years and older (P =NS).
After adjusting for recipient, donor, and transplant factors associated with graft loss, recipients aged 70 to 79 years had a HR of 1.26 (95% CI 1.20–1.33) and 80 years and older had a HR of 1.78 (95% CI 1.42–2.23) compared with the reference group of recipients aged 60 to 69 years. However, multivariate analysis showed no difference in death-censored graft survival for recipients aged 70 to 79 years (HR 1.02, 95% CI 0.93–1.11) and 80 years and older (HR 0.89, 95% CI 0.57–1.39) compared with the reference group of recipients aged 60 to 69 years.
There was no difference in the risk for graft failure with induction therapy compared with no induction among recipients 80 years and older. Using no induction as the reference, thymoglobulin had a HR of 0.78 (95% CI 0.39–1.57), IL-2 receptor antagonists had a HR of 0.68 (95% CI 0.34–1.36), and alemtuzumab had a HR of 1.11 (95% CI 0.44–2.79). Similarly, there was no difference in death-censored graft failure for thymoglobulin (HR 1.05; 95% CI 0.26–4.20), IL-2 receptor antagonists (HR 0.94; 95% CI 0.23–3.76), and alemtuzumab (HR 2.66; 95% CI 0.60–11.9) compared with no induction therapy.
Patient Survival of SCD and ECD Recipients 80 Years and Older
Among the 199 recipients 80 years and older, 65 received a standard criteria donor (SCD) kidney (33%) and 85 received an ECD kidney (43%). Figure 2 shows an unadjusted patient survival curve comparing SCD and ECD transplant recipients 80 years and older. There was no difference in survival during the follow-up period (P =0.98). Patient survival at 2 years was 73% for SCD recipients and 72% for ECD recipients.
FIGURE 2.:
Unadjusted patient survival of standard criteria donor (SCD) and expanded criteria donor (ECD) recipients 80 years and older.
DISCUSSION
Kidney transplantation is predicted to have a survival advantage over dialysis; however, this benefit diminishes with advancing age (1 2
The majority of ESRD patients 80 years and older are not considered for kidney transplantation. In 2007, only 0.6% of prevalent dialysis patients in the United States were on the wait list for a kidney transplant (2
Beginning at 105 days after transplant, we observed decreased patient survival in recipients 80 years and older compared with those aged 60 to 69 and 70 to 79 years. Survival of recipients 80 years and older decreased at a faster rate compared with their younger counterparts. This trend is comparable with that seen in the general population, where the mortality rate of an 80-year-old recipient is more than three times greater than that of a 60-year-old recipient (3 2
There were proportionally more ECD kidneys used with increasing age. We found no difference in patient survival up to 2 years between SCD and ECD kidney recipients 80 years and older. This suggests that donor quality has little impact on intermediate-term mortality (up to 2 years) in recipients 80 years and older, although we did not adjust for recipient factors or differences in waiting time because the number of events was small. It is possible that with time, a difference in mortality may become apparent, and further studies are needed to evaluate this.
There is a paucity of data in the literature regarding the use of induction therapy in the elderly, although it has been suggested that IL-2 receptor antagonists should be favored over depleting antibodies, given its more favorable safety profile (4
Our study found that the majority of recipients 80 years and older were whites (87.9%) and men (82.9%). Multiple studies have reported that women have decreased access to transplantation as defined by lower rates of listing for kidney transplant when compared with men (5–7 7 7 8, 9 10–13
Previous studies have indicated that kidney transplantation in the elderly has been associated with improved quality of life in comparison with remaining on dialysis (14, 15
Our study is limited by a relatively short follow-up period. Because of a small sample size of transplant recipients 80 years and older, the number at risk beyond 2 years was insufficient to make reliable inferences. A longer follow-up period might accentuate the trend toward decreased survival observed among the older age groups in our study. Although we did not observe a difference in death-censored graft loss between recipients aged 80 years and older and those aged 60 to 69 and 70 to 79 years in our study, it is possible that differences could emerge with a longer follow-up period, and future studies are needed to evaluate for this.
In conclusion, patients 80 years and older represented 0.6% of elderly kidney recipients (age ≥60 years) transplanted from 2000 to 2008 in the United States. Overall perioperative mortality among elderly transplant recipients was low (1.5% at 30 days), although there was a trend toward increased perioperative mortality among those aged 80 years and older (2.5%). After 105 days, the risk of mortality became significantly higher among recipients aged 80 years and older compared with those aged 60 to 69 years. Recipients 80 years and older were not at higher risk for death-censored graft failure. No difference in mortality among SCD and ECD recipients 80 years and older was observed. Transplant centers can take into account these findings when counseling potential transplant recipients 80 years and older.
METHODS
A retrospective cohort study was conducted using data from OPTN/UNOS as of November 27, 2009. To study the outcomes of kidney transplant recipients 80 years and older, we compared their outcomes with elderly recipients 60 years and older. The cohort was stratified into three groups according to recipient age: 60 to 69, 70 to 79, and 80 years and older. Beginning in 2000, there was an increase in the number of patients 80 years and older who received kidney transplants. Therefore, we chose January 1, 2000 as the start of the study period and included all patients 60 years or older who received a kidney transplant from January 1, 2000 to December 31, 2008. Recipients of multiorgan transplants were excluded.
Recipient, donor, and transplant characteristics were described using medians (with 25th and 75th percentiles) and frequencies, as appropriate. Between-group comparisons were made using the Kruskal-Wallis test for continuous variables and chi-square test for categorical variables. Follow-up records were used to compare the median length of the initial transplant hospitalization and early complications, including the rate of DGF (defined as the need for dialysis in the first transplant week), primary nonfunction, and acute rejection during the initial hospitalization and at 1 year.
The Kaplan-Meier product limit method was used to generate patient, graft, and death-censored graft survival curves according to age category, SCD, and ECD status. Comparisons between groups were made with the log-rank test. Stepwise regression models were used for patient and graft survival analyses. Covariates included in the model were transplant year, recipient age, recipient gender, recipient race, dialysis duration, retransplantation, peak panel reactive antibodies, recipient comorbidities (diabetes, cardiovascular disease, peripheral vascular disease, and cerebrovascular disease), donor type, donor age, degree of human leukocyte antigen mismatch, induction therapy, tacrolimus, mycophenolate, and steroid use at discharge from the initial transplant hospitalization. All factors significant on univariate analysis (P <0.10) were included as covariates in the multivariate model. Results were expressed as HRs with 95% CIs and associated P values. P values were two tailed, and values less than 0.05 were considered significant. All analyses were conducted using STATA version 9.2 (College Station, TX).
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