Introduction

In the United States, kidney transplantation is increasing in patients over 65. This corresponds to an overall increase in End Stage Renal Disease (ESRD) which is projected to continue into the future [1]. Older adults make up the majority of those with End Stage Renal Disease, and according to national data, they continue to be transplanted at lower rates than others [2]. Compared to their younger counterparts, older patients were less likely to be listed and less likely to receive their first transplant [3]. Older adults are also removed from the waitlist and die on the waitlist at a higher rate than younger counterparts [2]. This is likely related to multiple factors, including stringent selection criteria, decreased interest among older patients, or a perception of limited utility of kidney transplantation in this population. This paper will review the most current literature of renal transplantation in an older population and suggest how transplantation of this group is best approached.

Renal Transplantation in Older Adults is Better Than Dialysis

On a very basic level, renal transplantation within any population has to have better outcomes than patients remaining on dialysis. Multiple publications have studied the outcomes of transplantation in older populations and compared survival on hemodialysis to survival following transplantation. Rao et al demonstrated dialysis patients 70 years of age or older have a 41% lower overall risk of death compared with wait-listed candidates [4]. Further, renal transplant prolongs survival across candidates of all adult ages including 70 years of age and older, and a variety of wait times [5]. Even receiving a kidney from a deceased donor kidney that is of 80 years of age or older has better survival outcomes than staying on dialysis [6]. In 2010 a review article done by Huang et al, the authors compiled international data showing that renal transplantation in older adults led to decreased mortality when compared to staying on the waitlist [7]. Five year survival after kidney transplantation for recipients aged 75 years or greater in the United States was found to be 59.9% for a live donor transplant, compared 40.3% for recipients of deceased donor kidneys, 29.7% for dialysis patients waiting for transplant , and 12.5% for those who were not selected for kidney transplantation and remained on dialysis [8]. Although not statistically significant, a group from Norway showed in recipients older than 65 that were receiving their first vs second transplant, death censored 5 year graft survival (90% vs 88%) was similar [9].

Outcomes in Older Patients Compared to the Young

In 2012, a review of SRTR data from 145,470 kidney transplant recipients by Molnar et al. studied outcomes in older adults for living donor renal transplantation and extended criteria donors [10]. The authors found death censored graft failure was somewhat high for recipients 75 years or older ( up to age 83 years); extended criteria donor kidneys were significant predictors of mortality in patients less than 70 but not in patients older than 70; and living donor renal transplant was associated with better survival in all patients less than 70 when compared to cadaveric donors [10]. A single center study reviewed 271 cadaveric renal transplant recipients and found patients older than 60 had comparable 1,3, and 5 year graft survival, episodes of rejection, major infections, and overall patient survival when compared to recipients younger than 60 years of age [11]. The survival benefit seen in the Huang et al study encompassed those who received extended criteria donor organs, but when compared to younger recipients, the older patients did not live as long [7]. The author’s observation for this is that most older patients die with a functioning graft, so inherit comorbidities of transplanting an older population may be the etiology for the observed decrease in graft and patient survival [7]. Not surprising, OPTN (Organ Procurement and Transplant Network) data showed a similar finding of 4.4-times higher risk of mortality after transplant in patients age 70 years or older vs those that were age 35– 49 [12]. Reviewing Scientific Registry of Transplant Recipient (SRTR) data, Huang et al in a different study showed that in patients 65 years and older, death censored graft loss was similar between recipients with a prior non-kidney solid organ transplant and those that did not have a prior non-kidney solid organ transplant [13].

Outside of the United States, the subject of renal transplantation in an older population has also been an area of interest and study. In Poland, data was collected from 328 transplant recipients in which a cadaveric donor had both kidneys procured, but one kidney was given to patients around 65 years of age (standard deviation 4 years), and the other kidney was given to a younger recipient aged 45 years (standard deviation 12 years) [14]. They found that one-year post-transplant GFR, one-year patient mortality, one-year graft survival, episodes of DGF, and episodes of acute rejection did not differ between the two groups [14]. Overall long-term patient and graft survival were worse for the older population, but death censored long term graft survival was the same, suggesting what other studies have shown that older patients usually die with a functioning graft, most likely from age associated comorbidities [14]. A systematic review published in 2023 out of Europe included 19 articles for a total of 293,501 kidney transplant patients reviewing kidney transplant in 70 year olds compared to younger recipients found that overall survival was worse for older patients at all time points [15]. However, graft survival 3 years and less, acute rejection, delayed graft function, and death with functioning graft were not inferior in the older compared to the younger population [15]. Using the ANZDATA registry, 10,651 transplant recipients were reviewed in Australia and New Zealand from 2000 to 2015 [16]. They noted poorer overall survival for the older patients, but comparable rates of delayed graft function, and in living donor renal transplant older recipients, lower rates of acute rejection [16]. Norway showed that 5-year death censored graft survival of renal transplant recipients was 89% in what they deemed “elderly” (quartile age range 71.8-75.9), 88% in “seniors” (quartile age range 62.3-67.3), and 90% in their control group (quartile age range 47.6-52.4) [17]. Comprehensively, the available literature on transplantation in older patients shows that results can be acceptable with the appropriate candidates.

Living Donor Studies in Older Adults

A study of 830 living donor kidney transplant recipients in Japan between 2000 and 2011 found no significant difference in death censored graft survival over a ten-year period in patients older than 60 years of age and those younger [18]. Patient overall survival was decreased for the older group, however, the authors concluded that the decreased patient survival was related to normal age related comorbidities [18]. A group from Korea compared nearly 5000 kidney transplant recipients in a national registry and compared patients older than sixty years of age and younger [19]. There were several interesting findings in this study relating to patients over sixty including no difference in biopsy proven rejection, higher all-cause mortality in living donor kidney transplant recipients, higher rates of infection, and increased mortality following desensitization in the older population [19]. These studies reiterate the previously discussed acceptable outcomes in this patient population.

Readmission, Mortality Causes, Quality of Life, and Economic Factors

Readmission following renal transplant continues to be a large burden for the current healthcare system. Huagen et al reviewed 22,458 Kidney Transplant (KT) recipients 65 or older vs 86,372 KT recipients that were younger than 65 but older than 17, and noted that the older patient was more likely to be readmitted within the 30 day post op period than the younger patients are [20]. Early hospital readmission was noted to be a higher risk of graft loss in the older group, but a higher rate of mortality in the younger group [20]. Falls also comprise a large source of readmission, morbidity, and healthcare spending. A serious fall is documented as either a claim or documented injury such as fracture, dislocation, etc [21]. A serious fall within a year prior to renal transplantation led to lower graft survival along with longer post-transplant hospitalization days, but post-transplant survival was similar to patients who did not fall [21].

At a single center in Italy, the causes of death for renal transplant recipients older than 65 were infections in 42%, tumors in 23%, cardiovascular disease in 14%, cerebrovascular disease in 7%, and unknown in 14% [22]. This suggests optimizing these conditions in the peri-transplant period would increase the longevity of patient and graft survival. Other transplant centers have suggested using “prehabilitation” strategies in order to optimize older patients before transplant such as a living donor renal transplant, which can be planned [23]. Renal transplantation can not only improve survival, but quality of life. In Australia, a cohort of 30 renal transplant recipients aged 65 to 80 found most patients felt able bodied enough to enjoy their new freedom, but a few felt uneasy about their slow recovery and unexpected comorbidities [24]. Toronto reviewed the economic impact of receiving a renal transplant, and assuming a two year wait time, renal transplantation was economically advantageous in patients 65 and younger, but less so in older patients and patients waiting longer than 2 years [25]. This suggests that living donation, as well as timely cadaveric transplant with extended criteria donors, may provide an economic advantage in the older transplant recipient to allow shorter wait times.

Frailty

Frailty has been a topic of debate in many surgical fields including transplantation. Frailty is defined as a clinically recognizable state of increased vulnerability resulting from aging-associated decline in reserve and function across multiple physiologic systems such that the ability to cope with everyday or acute stressors is comprised [26]. Frailty is more prevalent in older transplant recipients than young ones [27]. It is an important indicator of post kidney transplant mortality. Frailty measured by weight loss, low grip strength, low activity, and slow walking speed has been shown to increase post transplant mortality independent of age [28]. Thus, it is extremely important in older populations to screen, identify, and treat patients that are found to be frail both while on the wait list and before being placed on the wait list. Preoperative optimization with ERAS (Enhanced Recovery After Surgery) protocols have been studied in liver and colon surgery showing promising results, and could also be used in a living donor planned renal transplantation [29]. With dialysis having a higher mortality than transplantation, transplantation should be pursued, and frail patients optimized if able. Centers may be reluctant to pursue living donor renal transplantation in older patients, but prehabilitation strategies offer a way to optimize the frail patient before setting a date for the transplantation. Once defined as frail, programs need to reduce this as much as is possible with the hopes to bridge the patient to transplantation.

Protocols and the Sequelae of Immunosuppression in Older Transplant Recipients

Tailoring immunosuppression in older transplant patients is imperative given their increased risk of infectious complications [19]. In a single center review, infectious complications were compared between 91 renal transplant patients 40-60 years of age and 91 matched renal transplant patients older than 65 years of age [30]. They found higher rates of urinary tract infections and cytomegalovirus infections in the older recipient group, but no difference in pneumonias, blood stream infections, rejections, or graft loss between the two groups [30]. Another center explored episodes of acute rejection in 363 renal transplant patients with 281 being less than sixty years of age and 82 patients being older than 60 years of age [31]. What they found was similar incidence and Banff grading of acute rehection with younger patients having only a higher level of panel-reactive antibodies [31]. Walter Reed Army Medical center reviewed the rates of Post transplant lymphoproliferative disorder (PTLD) in 25,127 medicare patients [32]. What was found was that younger age was associated with a higher likelihood of developing PTLD, but older patients had poorer survival once PTLD developed [32].

For the above reasons, immunosuppression must be tailored appropriately in the older renal transplant recipient very carefully. Thus, Basiliximab is more commonly used in older populations with good success, and lower maintenance immunosuppression protocols have also been seen in older recipients [33]. Alemtuzamab appears to be inferior in older populations due to increased graft failure and patient mortality [33]. Most maintenance protocols use a form of CNI with an antimetabolite [33]. Steroid free protocols reduce fractures, PTLD, and malignancy in older patients [33]. The use of anti-thymocyte globulin (ATG) or alemtuzumab (ALEM) induction was less common in recipients 65 or older compared to those 18-64 years of age [33]. Older recipients also were more likely to receive interleukin (IL)-2-receptor antibody (IL2rAb) [33]. mTORi-based and cyclosporine-based regimens were associated with increased mortality in older patients as well [33]. Approaches to immunosuppression in older patients need to reduce the overall immunosuppressive state to balance the risk of rejection with the risk of post-transplant infection.

The East Carolina University Experience

At East Carolina University Medical Center, we have noted that our older patients have had comparable outcomes to their younger counterparts. We collected data from a total of 1524 kidney transplant patients between 1995 and 2020, and stratified them into two categories, age below 65 years (Group 1) and age 65 years and above (Group 2). One-, 5- and, 10-year graft survival rates were 92%, 62% and 32%, respectively, in Group 2 compared to 93%, 74% and 49% in Group 1 (<0.001). Cumulative probability of graft loss/death at 1-, 5- and 10-years post-transplant was 4%/3%, 15%/11%, and 27% /24% in Group 1 compared to 3%/6%, 8%/30%, and 13%/55%, respectively, in Group 2. When reviewing our center specific waitlist mortality rate reported in SRTR for the period of July 2021 to June 2023, the mortality rate ratio is better for the transplant candidates greater than sixty years (1.1) compared to transplant candidate ages 40-60 (1.89). We suspect the cause of this is multifactorial; including more stringent criteria for older patients to be waitlisted at our center and for more severe morbidity in patients that develop ESRD at a younger age. Additionally, the location of our center is in a largely rural and low-income area where access to care is limited. More analysis of this very complex issue is needed.

Conclusion

As the geriatric population increases and our ability to care for their comorbid conditions improve, we will see an increase in the number of older patients eligible for renal transplantation. Further studies in this field are needed to elucidate optimal ways to transplant this group. Currently, more specialized immunosuppression regimens, optimal antibiotic prophylaxis, increased usage of frailty assessments, and expanded use of alternative options than standard cadaveric donors, such as use of kidneys with high kidney donor profile index scores, and living donors, will all help improve our ability to transplant this ever increasing population. As our current population ages, we must do our best to investigate these topics further and provide transplantation as the treatment of choice in older adults to extend life longer than dialysis allows. Additional considerations should continue to be made for programs that transplant older adults at a higher rate. Recipients age is compensated for in programs transplant outcomes, and this can be seen in the risk adjustment model equations found on the website of the Scientific Registry of Transplant Recipients [34]. Clearly, older patients can benefit from transplantation compared with dialysis outcomes. However, due to their comorbidities, older patients will have decreased overall patient survival due to their age as demonstrated by equivalent death censored graft survival verses overall graft survival. As a community of transplant providers, we must continue to improve our care of older patients with ESRD and guard against preventing transplantation of this group by simplistic analyses of post transplant outcomes which do not always appropriately compensate for the challenges faced in caring for these individuals, see Table 1 for summary of articles used in the paper.

Table 1 Table of studies
Full size table

Key References

  • Rao PS, Merion RM, Ashby VB, Port FK, Wolfe RA, Kayler LK. Renal transplantation in elderly patients older than 70 years of age: results from the Scientific Registry of Transplant Recipients. Transplantation 2007;83:1069–74. [PubMed: 17452897].

    • Shows outcomes of older patients receiving a renal transplant is better than remaining on dialysis.

  • Huang E, Segev DL, Rabb H. Kidney transplantation in the elderly. Semin Nephrol. 2009 Nov;29(6):621-35.https://doi.org/10.1016/j.semnephrol.2009.07.011. PMID: 20006794; PMCID: PMC2849001.

    • A review of outcomes of renal transplantation in older transplant patient compiling many studies. Also compares outcome of younger recipients.

  • Lentine KL, Cheungpasitporn W, Xiao H, McAdams-DeMarco M, Lam NN, Segev DL, Bae S, Ahn JB, Hess GP, Caliskan Y, Randall HB, Kasiske BL, Schnitzler MA, Axelrod DA. Immunosuppression Regimen Use and Outcomes in Older and Younger Adult Kidney Transplant Recipients: A National Registry Analysis. Transplantation. 2021 Aug 1;105(8):1840-1849. https://doi.org/10.1097/TP.0000000000003547. PMID: 33214534; PMCID: PMC10576532.

    • A comprehensive review of current immunosuppression regimens in older renal transplant recipients.