During the follow-up period, 42 (39.3%) dialysis patients and 5 (7.5%) transplant patients died (P <0.001). The overall mortality rate was 0.096 per patient-year (0.131 for dialysis and 0.029 for transplant). Causes of death in the dialysis group included cardiovascular disease (59.5%), infection (19%), cerebrovascular disease (7.1%), malignancy (4.8%), dialysis withdrawal (4.8%), calciphylaxis (2.4%), and dementia (2.4%). In the transplant group, the causes of death included cardiovascular disease (40%), malignancy (40%), and pulmonary embolism (20%). All transplant patients died with functioning grafts and no renal allografts were lost other than because of patient death. Respective 1- , 3- and 5-year survivals were 92%, 62%, and 27% for the dialysis group and 98%, 95%, and 90% (P <0.01) for the transplant group (Fig. 1). Using Cox’s Proportional Hazards model with a time-dependent covariate to control for the time until transplantation, an adjusted hazard ratio of 0.16 (95% confidence interval 0.06 - 0.42) was calculated, in favor of transplant patients.
There were 51 patients in the dialysis group withdrawn at some time point after initial inclusion on the transplant waiting list. The indications for withdrawal included cardiovascular disease (45%), general poor health (15.7%), malignancy (7.8%), peripheral vascular disease (5.9%), cerebrovascular disease (3.9%), dementia (3.9%), patient preference for dialysis (3.9%), obesity (2.0%), depression (2.0%), amyloidosis (2.0%), noncompliance (2.0%), light chain deposition disease (2.0%), cirrhosis (2.0%), and progressive systemic sclerosis (2.0%). Withdrawals were intended to be permanent in 41 (78.8%) cases. Before withdrawal, only 22 (20.6%) dialysis patients had died (mortality rate=0.097 per patient-year). If patients were censored at the time of their withdrawal from the transplant waiting list, the adjusted hazard ratio was 0.24 (95% confidence interval 0.09 - 0.69), again favoring transplant patients (Fig. 2).
The results of the present study provide strong evidence that renal transplantation confers a substantial survival advantage over dialysis in older patients with end-stage renal disease who are considered “fit” enough to undergo transplantation. Specifically, older renal transplant recipients were 8 times less likely to die than waiting-listed, older dialysis patients. Even when dialysis patients who were no longer considered suitable for transplantation were censored after their removal from the waiting list, the hazard rate for transplantation was still 4 times lower than for dialysis. To our knowledge, this is the first analysis to demonstrate a propitious effect of renal transplantation on the survival of older patients, by applying a Cox regression model in a single-center study.
These results contrast with those of several earlier studies that failed to find a survival benefit of renal transplantation compared with dialysis (15–17). Sommer et al. (15) and Lundgren et al. (16) reported lower survival probabilities for older cadaveric renal transplant recipients compared with dialysis patients, whereas Hutchinson and associates (17) found no differences between the two treatments after adjustment for comorbid factors. Kyllonen and Ahonen (11) and Bonal and co-workers (10) both observed initially lower survival rates in older transplant populations compared with waiting-list dialysis populations at 12 months, followed by marginally better survival after 5 years. Most of these studies were notable for their high mortality rates in the early posttransplant period as a result of postoperative infectious and cardiovascular complications. It is possible, therefore, that some of the disparities between the results of these earlier studies and those of the present investigation reflect improvements in peri-operative management and immunosuppressive therapy that have outpaced concomitant advances in the delivery of dialysis (18, 19). Improved selection of renal transplant candidates may also have contributed (20, 21), because all of the previous studies had more liberal selection criteria for admission to their transplant waiting lists. Finally, “center effects” have been shown to be an important determinant of patient survival in both the transplant and dialysis settings (7, 22, 23) and could conceivably have accounted for some of the contrasting results between studies.
In keeping with the results of the current study, Schaubel et al. (7) reported greater 5-year survival rates for transplant recipients over 60 (81%) compared with matched, randomly-selected dialysis patients (51%). However, the findings in this report were potentially confounded by case selection bias because renal transplant candidates exhibit less comorbidity than the average dialysis patient (24). Thus, by comparing renal transplant recipients with the general dialysis population, rather than with transplant candidates, it is likely that the survival benefit of renal transplantation was overestimated. Fauchald and co-workers (9) attempted to address this issue by comparing the survival of older renal transplant recipients and transplant waiting-list dialysis patients. They observed superior survival in the transplant group at 6 months (93% vs. 64%), 12 months (87% vs. 44%), and 4 years (62% vs. 7%). However, the fact that the 4-year survival in the waiting-list dialysis population was actually worse than in the remainder of the dialysis population (7% vs. 13%, respectively) again raised the concern that the demonstrated benefit of transplantation was biased by differential overall health in the two populations. Although it is difficult to entirely exclude the possibility of such bias also existing in the present study, it is noteworthy that the two study populations were very well matched at the baseline for demographic variables, comorbid illness, and time undergoing dialysis. The higher proportion of non-Caucasians in the dialysis population most likely reflected a greater prevalence of uncommon major histocompatibility antigens not shared with those of an almost exclusively Caucasian donor pool. Diabetes was also more frequent in the dialysis population, but adjusting for this comorbid condition using multivariate regression only slightly reduced the impressive survival benefit of renal transplantation.
The survival probabilities of older transplant recipients at 1 year (98%), 3 years (95%), and 5 years (90%) are similar to or better than in previous reports (3, 7, 11, 15, 16, 18, 25–40) and are comparable to those of patients between 30 and 50 years who receive transplants at our center (97%, 94% and 92%, respectively) (12). Graft survival was identical to patient survival in our older patients because the only cause of graft loss was patient death. Numerous other studies have also reported that patient death is a far more significant cause of graft loss than rejection in older patients (12, 18, 35, 36, 41, 42). However, this should not necessarily be viewed as a waste of precious renal allografts because graft survival in older recipients was comparable with that reported in younger transplant patients (12). Other groups have described similar findings (32, 35, 36, 43, 44). Thus, the increase in graft loss because of patient death in the over 60 age group seems to be offset by a reduction in loss because of rejection.
It is also interesting to note in the present study that the annual mortality rate of patients in the waiting-list dialysis group (13%) was only marginally better than that reported for the general older dialysis population in Australia (25%) (2). This was so despite the fact that the former population was deemed to represent the healthiest tertile of older Queensland dialysis patients on the basis of a standardized and exhaustive screening protocol involving clinical, laboratory, and radiological assessments (including coronary angiography in many cases). We have previously demonstrated that the institution of this screening protocol has resulted in a profound improvement in the survival of patients over 60 after transplantation (12), suggesting that these “fitter” patients do only substantially better, provided they subsequently receive a renal transplant. Schaubel and associates (7) similarly observed that the effect of transplantation on survival was greatest among the healthiest group of older end-stage renal disease patients with no comorbid illnesses.
As found in other studies (9, 25, 45), the major cause of death in both the dialysis and transplant populations was cardiovascular disease (59.5% and 40% of deaths, respectively). It is interesting that infection accounted for 19% of deaths in the dialysis group, but did not contribute to the demise of any transplant patient. Because aging is itself associated with a reduced activity of cell-mediated immunity (3), transplantation in older patients is generally characterized by lower rejection rates and higher rates of viral, bacterial, and fungal infections (3, 9, 18, 25, 29, 46). Consequently, less immunosuppressive therapy is administered to older transplant recipients that young recipients in our unit, and this may have obviated the occurrence of fatal infectious events in this study.
The observation in the present study that older dialysis patients have improved longevity after kidney transplantation complements previous reports of significantly enhanced quality of life in such patients. In a prospective study of patients undergoing renal transplantation at three Canadian hospitals, Laupacis et al. (47) demonstrated that transplantation in individuals over 60 was significantly more cost-effective than dialysis and was associated with marked improvement in health-related quality of life, as measured by the Sickness Impact Profile and the Time Trade-Off Technique. Bonal and associates (10) also showed that patients older than 55 who received a renal transplant had superior functional autonomy compared with their waiting-list dialysis counterparts. Moreover, Hestin et al. (35) observed that functional rehabilitation and quality of life were as good in renal allograft recipients over 60 as in younger recipients. Thus, denying transplantation on the basis of age alone seems to be difficult to justify.
In conclusion, the present study suggests that renal transplantation seems to confer a substantial survival advantage over dialysis in older patients with end-stage renal failure who are rigorously screened and considered suitable for renal transplantation. Patient and graft survivals in such individuals are comparable to those in younger patients, indicating that older patients should not be rejected for transplantation purely on the basis of their age. Indeed, in patients over 60 who have minimal comorbidity, transplantation should be recommended as the renal replacement therapy of first choice.
The authors gratefully acknowledge the contributions of their nephrologist colleagues, Dr. Michael Falk, Dr. Ed Meagher, Dr. Alan Parnham, Dr. Amir Alamir, Dr. Peter Craswell, Dr. Phil Boyle, Dr. Peter de Jersey, Dr. Tim Furlong, Dr. Emlyn Jones, Dr. Simon Fleming, Assistant Professor Zoltan Endre, Dr. David Saltissi, and Dr. Helen Healy, who co-operated with the screening protocol and provided ongoing patient care after the early posttransplant phase. The authors also thank the nursing staff of our unit (particularly Sister Joan Allen) for their expert patient care.
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