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To inform decision making regarding transplantation in patients ≥ 65 years, we quantified the early posttransplant risk of death by determining the time to equal risk and equal survival between transplant recipients and wait-listed dialysis patients in the United States between 1995 and 2007 (total n = 25 468). Survival was determined using separate multivariate nonproportional hazards analyses in low-, intermediate- and high-risk cardiovascular risk patients. Compared to wait-listed patients with similar cardiovascular risk, standard criteria (SCD) and expanded criteria (ECD) recipients had a higher risk of death in the perioperative and early-posttransplant period. In contrast, low and intermediate risk living donor (LD) recipients had an immediate survival advantage compared to similar risk wait-listed patients. In all risk groups, transplantation was associated with a long-term survival advantage compared to dialysis, but there were marked differences in time to equal risk of death, and time to equal survival by donor type. For example, survival in high-risk recipients of an LD, SCD and ECD transplant became equal to that in similar risk wait-listed patients 130, 368 and 521 days after transplantation. Early posttransplant mortality risk is eliminated in low- and intermediate-risk patients, and markedly reduced in high-risk patients with LD transplantation.
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Kidney transplantation is the preferred treatment for patients with end-stage renal disease (ESRD), because it is associated with increased long-term survival and improved quality of life compared to treatment with dialysis [1, 2]. The benefits of transplantation are present in both young and old patients . However, the survival advantage of deceased donor kidney transplantation is not recognized for approximately 8 months after the transplant surgery because of increased mortality during the perioperative and early posttransplant period, that is primarily due to cardiovascular disease . The early mortality risk is likely higher in elderly patients because of age and a higher burden of comorbid disease, but also because elderly patients frequently undergo transplantation with older deceased donor kidneys that have a higher perioperative complication rate.
The physiological stress of transplant surgery is likely greater with a deceased compared to living donor. Deceased donor transplantation is uniquely an elective procedure involving patients at risk for cardiovascular disease performed under emergent conditions. Wait-listed patients summoned for urgent transplantation may not be medically optimized for surgery and a variety of unpredictable issues with the deceased donor kidney may complicate the transplant operation. In contrast, living donor transplantation provides an opportunity to optimize recipient medical management. Surgical considerations including the presence of recipient vascular disease and variation in donor anatomy are identified in advance of surgery and slow or delayed graft function is far less common than in deceased donor transplantation. To inform decision making regarding the use of different types of donors in the elderly, we quantified the early posttransplant risk of mortality by determining (1) the time to equal risk of death and (2) the time to equal survival between transplant recipients ≥ 65 years of a standard criteria deceased donor (SCD), expanded criteria deceased donor (ECD), or living donor (LD) and wait-listed dialysis patients of similar age and cardiovascular risk.
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The characteristics of n = 25 468 study patients, including n = 11 425 (45%) low, n = 3 038 (12%) intermediate and n = 11 005 (43%) high cardiovascular risk patients are shown in Table 1. During the median follow-up of 2.67 (1.30, 4.78) years, n = 11 072 (43%) received a transplant including n = 5 825 (51%) of the low risk patients; n = 1 397 (46%) of the intermediate risk patients and n = 3 850 (35%) of the high-risk patients. During follow-up there were n = 6540 (25%) deaths on waiting list including n = 2289 (20%) of the low risk patients; n = 850 (28%) of the intermediate risk patients and n = 3401 (31%) of the high-risk patients. The risk of death was higher in patients with delayed graft function (DGF). The death rate in low-, intermediate-, and high-risk patients with DGF was 17, 15, 23 per 100 patient years compared to 4, 8, 10 per 100 patient years among those in the same risk groups without DGF. A total of n = 1489 patients (6%) were removed from waiting list including n = 633 (6%) of the low-risk patients; n = 185 (6%) of the intermediate risk patients and n = 671 (6%) of the high-risk patients. Among the 11 072 transplant recipients n = 3 600 (33%) died after transplantation, including n = 1 548 (27%) low risk, n = 468 (34%) intermediate risk, n = 1 584 (41%) high-risk patients). The use of SCD, ECD and LD transplantation was similar in low, intermediate and high-risk patients (Table 2). Preemptive transplantation was more frequent in low-risk patients, and median waiting times among nonpreemptive recipients were 1.0–1.2 years (Table 2).
Table 1. Patient characteristics (N = 25 468)
| ||Low risk||Intermediate||High risk|| |
| ||N =||N =||N =|| |
| ||11 425||3038||11 005||p-Value|
|Mean age (+/− SD)||70 (4)||70 (4)||69 (3)||<0.001|
|Male sex (%)||60||69||65||<0.001|
|Race (%)|| || || ||<0.001|
|Comorbid conditions (%)|| || || ||<0.001|
|Ischemic heart disease|| ||42||31|| |
|Congestive heart failure|| ||36||32|| |
|Peripheral vascular disease|| ||13||15|| |
|Cerebrovascular disease|| ||9||8|| |
|Diabetes as only risk factor|| ||NA||10|| |
|Cause of ESRD (%)|| || || ||<0.001|
|Polycystic disease||10||8||2|| |
|Year of waiting list (%)|| || || ||<0.001|
Table 2. Use of standard criteria, expanded criteria and living donor transplantation by the patient cardiovascular risk group
| ||Low risk||Intermediate risk||High risk|
| ||N = 5825||N = 1397||N = 3850|
|SCD N (%)||2627 (45%)||638 (46%)||1760 (46%)|
|Median waiting time||1.1 years||1.0 years||1.1 years|
|ECD N (%)||1713 (29%)||425 (30%)||1210 (31%)|
|Median waiting time||1.2 years||1.1 years||1.1 years|
|Living donor N (%)||1485 (25%)||334 (24%)||880 (23%)|
|Median waiting time||0.49 years||0.45 years||0.49 years|
Figure 1 shows the multivariate adjusted risk of death in transplant recipients of LD, SCD and ECD kidneys compared to patients of similar cardiovascular risk who remained on the waiting list. In all patient risk groups, the risk of death in transplant recipients compared to wait-listed patients varied with time after transplantation (Figure 1). In all patient risk groups, the risk of death was highest in ECD recipients, followed by SCD and LD recipients. Living donor transplantation was associated with an immediately lower risk of death compared to treatment with dialysis in low risk and intermediate risk patients (Figure 1). In all patient risk groups, the death rate in the first year after transplantation was lowest in LD recipients, followed by SCD and ECD recipients (Table 3). The time to equal risk, and time to equal survival in transplant recipients compared to patients of similar risk who remained on dialysis, was related to donor source (Table 3). LD transplantation was associated with an immediately lower risk of death in low risk and intermediate risk patients, and an equal risk of death after 43 days and equal survival after 130 days in high-risk patients. In comparison the times to equal risk and equal survival were longer in SCD recipients, with the longest times observed in ECD recipients (Table 3). Table 4 shows the time to equal risk, and equal survival by tertile of KDRI among deceased donor recipients. Recipients of the lowest tertile KDRI transplants had the lowest time to equal risk of death, and the lowest time to equal survival.
Table 3. Death rate, days to equal risk of death and days to equal survival by donor type and patient cardiovascular risk group
|Death rate on waiting list/100 patient years||14|
|Death rate/100 patient years during first posttransplant year||8||10||3|
|Days to equal risk||90||95||Immediately lower risk|
|Days to equal survival||203||264||Immediately higher survival|
|Intermediate risk patients|
|Death rate on waiting list/100 patient years||17|| || |
|Death rate/100 patient years during first posttransplant year||9||14||3|
|Days to equal risk||96||110||Immediately lower risk|
|Days to equal survival||285||470||Immediately higher survival|
|High risk patients|
|Death rate on waiting list/100 patient years||22|| || |
|Death rate/100 patient years during first posttransplant year||11||16||6|
|Days to equal risk||110||180||43|
|Days to equal survival||368||521||130|
Table 4. Days to equal risk of death and days to equal survival by tertile of the kidney donor risk index
| ||KDRI <1.05||KDRI 1.05–1.51||KDRI >1.51|
|Days to equal||Immediately||61||102|
| risk||Lower risk|| || |
|Days to equal||Immediately||178||365|
| survival||Higher survival|| || |
|Intermediate risk patients|
|Days to equal||Immediately||75||175|
| risk||Lower risk|| || |
|Days to equal||Immediately||185||435|
| survival||Higher survival|| || |
|Days to equal risk||82||95||181|
|Days to equal survival||225||302||525|
Figure 1. The multivariate adjusted relative risk of death in low (first panel), intermediate (second panel) and high (third panel) cardiovascular risk patients. In each panel the multivariate adjusted risk of death in living donor (LD, shown in red), standard criteria deceased donor (SCD, shown in purple), or expanded criteria deceased donor (ECD, shown in green) transplant recipients is compared to that in wait-listed patients of similar cardiovascular risk (shown in blue) who had been on dialysis for equal lengths of time but who had not yet received a kidney transplant. In all cardiovascular risk groups, the risk of death immediately after SCD and ECD transplantation was higher than that among wait-listed patients of similar cardiovascular risk. In contrast, the risk of death in low and intermediate cardiovascular risk recipients was immediately lower than that in similar risk patients who remained on the waiting list. The long-term risk of death was lower with transplantation in all risk groups and with all donor types.
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The donor-related differences in death rate, days to equal risk and days to equal survival also varied by recipient risk: The smallest differences were observed in low-risk patients with larger differences in intermediate and high-risk patients (Table 3).
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Quantification of the early risk of death in elderly transplant recipients from different donor sources in this study may be useful to care providers when counseling patients about their transplant options. The study demonstrates that despite significant efforts to minimize the early risks of deceased donor transplantation, this risk remains a barrier to transplantation for elderly patients. The study shows that living donor transplantation is the safest strategy to increase transplantation in this patient group, and the results should help expand the use of living donor transplantation in ESRD patients ≥ 65 years. The relevance of these findings may increase in the future because proposed changes to the deceased donor kidney allocation in the United States may limit opportunities for SCD transplantation in this age group . Finally the study confirms the importance of DGF as a risk factor for early mortality and suggests that strategies to reduce DGF could improve early survival in elderly patients .
In low cardiovascular risk patients, LD transplantation was associated with an immediate survival advantage compared to dialysis; however, the greatest risk reduction was seen in intermediate cardiovascular risk patients where the time to equal survival was reduced from 470 days with an ECD transplant to zero days with a LD transplant. Although LD transplantation was associated with an increase in early mortality in high cardiovascular risk patients, the risk reduction as quantified by the time to equal survival (reduced from 521 days with an ECD transplant to 130 days with a living donor transplant) was still greater than that observed in low-risk patients (time to equal survival reduced from 264 days with an ECD transplant to zero days with a living donor transplant). These findings should help address concerns regarding the use of living donors in elderly transplant candidates with a history of cardiovascular disease. However, the excess early mortality after living donor transplantation in high-risk patients remains an important consideration that should be discussed with patients and their potential donors.
Although the likelihood of transplantation among the elderly increased twofold over the last decade, only 7% of ESRD patients ≥ 65 years are transplanted after 3 years of dialysis initiation . In part this is due to high mortality on the waiting list, with a recent analysis demonstrating that the 5-year probability of deceased donor transplantation in patients aged ≥ 65 years is nearly equal to the probability of death on the waiting list . Despite these statistics, many elderly patients and their care providers may be reluctant to pursue living donation. Offspring to parent donations account for only 1.5% of living donor transplants among recipients > 55 years , suggesting a reluctance to proceed with living donor transplantation when there is a significant difference in donor and recipient age. Younger patients may be more willing to accept living donation , but few studies have specifically examined the acceptance of living donation in elderly patients, or the willingness of individuals to donate to older patients.
It is important to recognize that although our findings favor the use of living donation in the elderly, transplantation from any donor source was associated with a reduced long-term risk of death compared to treatment with dialysis. Nonetheless the quantification of the time to equalize risk and to equalize survival compared to continued treatment with dialysis may be used to counsel some high-risk patients to only consider transplantation from a living donor. Therefore it is important to note that elderly patients in this study received deceased donor transplants after a median waiting time of only 1.0–1.2 years and it may take longer to equalize risk and survival in patients with longer waiting times. Similarly, we did not include deaths after removal from the waiting list, because we could not verify the indications for wait-list removal. Inclusion of deaths after delisting would likely decrease the time for the risk of death and survival to equalize between transplant recipients and wait-listed patients.
The study highlights the perioperative and early posttransplant period as a barrier to transplantation in elderly patients who could derive a long-term survival advantage if they could be successfully transplanted. Cardiovascular disease is the leading cause of death during the early-posttransplant period . Previous studies have highlighted the importance of coordinated care between dialysis and transplant physicians in order to optimize the medical management of cardiovascular risk factors in wait-listed candidates ; however, no strategy or intervention has been shown to reduce cardiovascular mortality during the early-posttransplant period . To date most studies have focused on identification of high-risk transplant candidates, and strategies to monitor and maintain the medical fitness of wait-listed patients, but no studies have specifically proposed donor selection as a strategy to minimize early posttransplant risk. The finding that wait-list removals were identical among low, intermediate and high-risk patients despite difference in wait-list mortality highlights the need to develop protocols for systematic reevaluation and wait-list removal of transplant candidates with a decline in health status during wait listing.
This study uses similar methods employed by Wolfe and colleagues  and extends those findings by providing more current information that is specific to the elderly population, and by quantifying risk with transplantation from different donor sources. The study by Wolfe and colleagues included only about 3000 deceased donor recipients ≥ 60 years. The estimation of time to equal risk and equal survival in this study was determined in transplant recipients compared to similar risk patients who remained on the waiting list and differs from that in the study of ECD transplantation by Merion and colleagues . In that analysis outcomes after ECD transplantation were compared with continued waiting on the deceased donor waiting list and transplantation from a standard criteria deceased donor. As a result the times to equal risk and equal survival among ECD recipients in the Merion study are longer than those among ECD recipients in this study.
Readers of this study should be aware of the inherent limitations of observational studies and the limitations of secondary analyses of registry data. Although our multivariate analyses adjusted for differences in a variety of factors that impact transplant outcome, there are undoubtedly unaccounted differences between LD, SCD and ECD recipients in this study that may confound our findings. Although the study included all elderly transplant recipients in the United States, the results may be difficult to apply to individual patients. The classification of cardiovascular risk in this study is not validated. Cardiovascular risk was classified based on history of comorbidities recorded at the time of first treatment for end-stage renal disease and does not include assessment of the severity of individual comorbid conditions.
In summary, the quantification of the early risk of transplantation from different donors sources in this study demonstrates that LD transplantation is the safest transplant option for elderly patients. These findings may be useful in counseling elderly patients about their transplant options, and may help expand the use of living donation in this patient group. The findings also highlight the need for strategies to minimize the early risk of mortality in the elderly.