The elderly have benefited from increased access to renal transplantation in recent years. New allocation concepts would shift distribution of kidneys to younger recipients, making expanded criteria and living donor kidneys more relevant for seniors. Current issues impacting expanded criteria donor kidney availability and living donor transplant opportunities for the elderly are explored. It is hoped that the kidney donor profile index will improve risk assessment and utilization of marginal kidneys. The usefulness of procurement biopsy remains controversial. Dual kidney transplantation and machine perfusion appear to be effective mechanisms to increase organ availability. “Old-for-old” allocation systems, donation service area variation and regulatory and reimbursement issues highlight disparities and disincentives affecting expanded criteria donor organ utilization, and considerations for the way forward are discussed. Living donor transplantation, even with older donors, may provide the best option for elderly recipients, and careful expansion of the living donor pool appears appropriate. In light of new allocation concepts, it will be important to understand issues pertinent to seniors and develop effective strategies to maintain or improve their access to the benefits of transplantation.
According to the Organ Procurement and Transplantation Network (OPTN) and the Scientific Registry of Transplant Recipients (SRTR), the proportion of persons listed for kidney transplant aged 65 and over increased faster than all younger age groups over recent years, accounting for 16.7% of the active list by the end of 2008 (2009 OPTN/SRTR Annual Report). Analysis of United States Renal Data System (USRDS) data (1) optimistically reported access to transplantation for incident end-stage renal disease (ESRD) patients aged 60–75 actually doubled between 1995 and 2006, largely due to threefold increase in likelihood of living donor renal transplantation (LDRT) as well as expanded criteria donor (ECD) transplantation. More recently, access to transplantation has appeared to remain stable for patients aged 65 or older in comparison to younger adults who have higher rates of transplant but have shown downward trends (Figure 1).
The OPTN/United Network for Organ Sharing (UNOS) Kidney Transplantation Committee (KTC) began a comprehensive review of national kidney allocation in 2005 in response to widespread concerns that the current system based primarily on waiting time results in excessive loss of potential graft years. Inefficient placement of ECD kidneys also leads to high discard rates of otherwise transplantable kidneys. New concepts released for public review in early 2011 proposing survival matching to allocate the top 20% of kidneys with lowest risk and relatively straightforward age matching within +/− 15 years of donor age to allocate the remaining 80% would bring about a substantial shift in distribution of deceased donor kidneys to younger recipients (Figure 2), with organs from older donors at higher risk of graft failure allocated primarily to older individuals. This would be projected to potentially cut the number of deceased donor renal transplants (DDRTs) by 658 or 16% for patients aged 50–64 and by 521 or 32% for those aged 65 and older over a year compared to allocation based on current rules (http://optn.transplant.hrsa.gov/kars.asp, accessed August 20, 2011). Considering recent trends in transplantation of the elderly in the context of new allocation concepts, ECD and living donor kidneys may become the most realistic options for timely transplantation of seniors. Current issues influencing ECD kidney availability as well as living donor opportunities for the elderly are herein reviewed, along with relevant considerations for potential future strategies to maintain or improve access to transplantation for seniors (Table 1).
Table 1. Issues influencing availability of ECD kidneys and living donor opportunities for seniors and potential strategies to maintain or improve access to transplantation for the elderly
Use of KDPI with enhanced granularity over SCD/ECD dichotomy
Increased selectivity in practice and uniform comprehensive reporting of findings
Dual kidney transplants
Increased application and consideration of unilateral procedure
Increased use of machine perfusion
More efficient sharing
Increased emphasis on shorter CIT and appropriate recipient selection
Regulation and reimbursement
Appropriate donor and recipient risk adjustment for performance metrics and reimbursement to minimize disincentives
Increased consideration of older donors and those with isolated medical abnormalities
Clinical Donor Risk Scoring
Despite an aging population, the proportion of deceased kidney donors aged 65 and older has remained relatively stable, fluctuating between 6.8% and 8.1% between 1999 and 2008. The number of ECD kidney donors yearly increased from 1091 to 1633, correlating with modest increase in their percentage of the deceased donor pool from 20.3% to 22.7%, and the number of ECD kidney recipients yearly increased from 1218 to 1792, with their proportion of all DDRTs increasing from 15.1% to 17.0% over the same time span (2009 OPTN/SRTR Annual Report). The discard rate of ECD kidneys, reported at 42.5% in 2008, has not changed significantly since introduction of the system to allocate these organs in 2002. It has been suggested that the ‘all or none’ standard criteria donor (SCD) versus ECD designation to describe organ quality is perhaps inadequate and this arbitrary line between “good” and “bad” organs may contribute to discard of “less than perfect” kidneys even though these organs would be predicted to provide survival benefit over dialysis for appropriate recipients (2). The increase in discard rate for the lowest risk ECD kidneys following institution of the policy raises the possibility that organs previously readily accepted for transplant were subsequently viewed as marginal (3). There is great variability in donor organ quality which is not captured by the SCD/ECD dichotomy. In this regard, the kidney donor profile index (KDPI) has been proposed as an allocation tool by the KTC to improve risk assessment of ECD kidneys. The KDPI, based on the kidney donor risk index (KDRI) previously described by Rao et al. (4), incorporates multiple donor and transplant parameters beyond those utilized for the ECD designation into a single metric quantifying risk for graft failure along a continuum. The KDPI has not achieved universal acceptance as a pivotal concept upon which to base new allocation policy focused on survival matching, as is currently proposed. The index, derived from a retrospective analysis of SRTR data, has never been prospectively validated. It is recognized that there may be significant donor risk factors not captured by the index which will become apparent with greater utilization of higher risk organs with such factors in the future (4). Concordance statistics indicate that the tool is more useful for distinguishing more extreme categories of graft failure risk, rather than comparing kidneys in the middle ranges for which it will carry a higher probability of error. Therefore, some have expressed lack of confidence in the index as a prognostic tool due to its unproven accuracy and reliability (5).
Approximately 75% of ECD kidneys are biopsied (3); however, usefulness of a procurement biopsy in predicting outcome of marginal organs remains controversial. Biopsy findings are the most common reason for refusal of ECD organs (6); conversely, kidneys initially refused due to poor clinical parameters have been utilized with good outcomes following more specific histologic classification (7). Glomerulosclerosis (GS) is relatively simple to quantify, and therefore is commonly reported. A review of SRTR data noted a direct relationship between GS and odds of discard for ECD kidneys. Kidneys with > 20% GS were 12 times more likely to be discarded than those with < 5% GS. However, there was no clear correlation between GS and graft failure (3). Analysis of OPTN/UNOS data reported that kidneys with > 5% GS on a pretransplant biopsy had slightly decreased overall 5-year graft survival compared to kidneys with 0–5% GS (53.6% vs. 59.0%, respectively); yet, among the cohort of kidneys with > 5% GS, the degree of GS, even exceeding 20%, was not associated with graft failure (8). Retrospective reviews of registry data are inherently subject to potential selection bias, and in the SRTR analysis, only 17% of transplanted ECD kidneys with a biopsy had > 10% GS (3), indicating that transplanted kidneys with greater degrees of GS were carefully selected and likely had other more favorable clinical and histological features not captured in the SRTR database. These studies suggest, however, that appropriately selected kidneys with increased GS can be transplanted with acceptable outcomes (3,8). Other histopathologic features, in particular vascular changes such as arteriolar hyalinosis and fibrous intimal thickening have been increasingly cited as important factors influencing graft outcome (9,10). Scoring systems based on more comprehensive assessment of histopathology have been proposed to better predict risk of graft failure in marginal organs (7,11). Advocates point out that scoring systems based only on clinical factors derived from the general population of deceased donors with age carrying a relatively high weight may be of limited prognostic value when applied to a narrow population of elderly donors (12). Remuzzi et al. (13) reported a series of 62 recipients of kidneys from donors older than 60 years allocated for single or dual kidney transplant (DKT) on the basis of a predefined histopathologic scoring system (11) assessing vessels, glomeruli, tubules and interstitium. They achieved graft survival similar to that of single grafts from younger donors and substantially better than that of single grafts from donors over age 60 allocated without histologic evaluation (13). A metaanalysis reviewing marginal donor kidneys allocated for single or DKT on the basis of histologic criteria also reported graft outcomes comparable to those of low risk ‘ideal’ donor kidneys and superior to those of marginal kidneys allocated without histologic evaluation (14). Although histopathologic scoring systems have been reported as useful for selecting kidneys for single or DKT or discard in limited single center or regional studies, their ability to truly discriminate graft outcomes or risk for graft failure has not been validated in large controlled studies.
Dual Kidney Transplants
A review of UNOS/OPTN data (15) found that despite having higher donor risk characteristics, recipients of DKT, comprising 4% of transplants from donors aged 50 and over, had lower rates of delayed graft function (DGF) and similar allograft survival up to 4 years posttransplant compared to recipients of single ECD transplants (15). Excellent clinical results were reported in the aforementioned series of Remuzzi et al. (13) consisting mostly of DKTs (54 of 62 transplants), comparable to those achieved with “ideal” kidneys. These exceptional outcomes raise questions from a perspective of utility if perhaps substantial survival benefit over dialysis could be achieved for more patients if some DKTs were allocated as single grafts, and some discarded organs allocated as DKTs. Twenty-five percent of DKTs in the OPTN/UNOS review (15) did not meet criteria for dual allocation put forth by UNOS, raising similar issues. Concerns regarding DKT include the more extensive procedure and associated complications, typically occurring in an elderly recipient with limited physiologic reserve. Bilateral grafts may also make a future transplant more challenging. Ekser et al. (16) recently addressed these issues in a series of 100 unilateral DKTs. They reported surgical complication rates comparable to those of single kidney transplants and 3-year patient and graft survival rates of 95.6% and 90.9% respectively.
Machine Perfusion Versus Cold Storage
Recent reviews of SRTR data confirm the association between machine perfusion (MP) and reduced DGF (3,17), with more benefit in higher risk donors (17). This is relevant in that DGF increases 1-year mortality of elderly recipients (18). MP is also associated with greater utilization of ECD kidneys (3,17). Despite the higher utilization rate and greater propensity to use MP in higher risk organs, graft survivals of perfused and cold stored ECD kidneys have been reported as comparable (17). It has been projected that use of MP for all ECD kidneys in the United States would reduce their discard rate to approximately 30% and potentially result in over 150 additional kidneys for transplant per year (17). Recently, Moers et al. (19) reported a European randomized controlled trial assigning one kidney from 336 consecutive deceased donors to MP and the other to cold storage, with 1-year follow-up demonstrating improved graft survival as well as reduced DGF with MP. A subsequent report from this group verified these advantages for ECD kidneys (20). The higher initial cost of MP has been an impediment to more widespread application of this technique. However, retrospective analysis of USRDS data found that MP correlates with lower costs for the transplant hospitalization for ECD transplants, likely related to reduction in DGF (21). Similarly, cost-effectiveness modeling based in part on the favorable European results suggests that at 1-year posttransplant MP is more cost-effective than cold storage for both ECD and SCD kidneys (22). Normothermic perfusion is a potential extension of this technology showing promise in experimental models. Reported benefits include opportunities to target specific repair mechanisms to protect against ischemia/reperfusion injury, enhanced renal blood flow during reperfusion and more comprehensive assessment of organ viability prior to transplantation (23).
The Eurotransplant Seniors Program (ESP) preferentially allocates kidneys from donors older than 65 years to unsensitized recipients older than 65 years locally or regionally to minimize cold ischemia time (CIT) compared to standard centralized Eurotransplant allocation across seven countries. A recent report on the program's first 5 years claims graft and patient survival under the ESP for donor and recipient age ≥65 to be similar to that of a comparison group utilizing standard Eurotransplant allocation for donor and recipient age ≥ 60, but more remarkably indicates doubling in number of elderly donors, decrease in wait times for ESP participants, and significant reduction in CIT and DGF under the program (24). In 2008, Eurotransplant reported 19.9% of deceased kidney donors were over age 65 compared to 7.7% in the United States (Eurotransplant Annual Report 2010, 2009 OPTN/SRTR Annual Report). Eurotransplant has achieved graft survivals similar to the United States for comparable older donor transplants with substantially lower discard rates and without heavy reliance on biopsy (6). A US single-center experience (25) reported favorable results in a series of ECD kidneys allocated according to consensus guidelines (26) to unsensitized candidates over age 60 or diabetics over age 40. Notably, compared to a cohort of historical controls, the rate of donor kidney biopsy dropped substantially from 85% to 24%, CIT decreased from 16.4 to 7.4 h, and incidence of DGF decreased from 43% to 15%. One-year graft and patient survival were comparable in the two cohorts. The authors concluded that the ECD designation provided a description of organ quality that may obviate biopsy, decreasing CIT and reducing DGF rates (25). Whether “old-to-old” allocation such as the ESP experience can be broadly translated to the United States with similar encouraging outcomes is an interesting proposition. In drawing comparisons between US ECD allocation and ESP experiences, demographic patterns have been speculated to play a role in the disparity in utilization rates of marginal organs; for example higher overall procurement rates in the United States reflecting more aggressive pursuit of donors whose kidneys are ultimately unsuitable for transplant, or relatively lower rates of living donation in Europe resulting in greater willingness (or necessity) to accept older deceased donor kidneys (6). More plausible is the assertion that candidate listing for older donor kidneys by the ESP is more appropriate and uniform with less reliance on procurement biopsy compared to ECD allocation in the United States, resulting in more efficiency, shorter CIT and greater utilization of organs (6).
Donation Service Area (DSA) Variation
DSA discard rates for ECD kidneys have been reported to vary widely from 14% to 60% (3). This variability is not attributable to differences in prevalence of donor risk factors, highlighting the reality that different DSAs have different thresholds of acceptance for ECD kidneys. Potential reasons underlying these variations in practice are complex, not well understood, and may involve DSA waiting time, composition of the waiting list, likelihood of receiving a non-ECD kidney and different needs for and attitudes toward ECD organ transplantation (3). From a utility perspective, this is a potential source of inefficiency and resource wastage, as kidneys discarded in some DSAs may be readily transplanted in others. DSA variation and its implications are being currently addressed by the OPTN and the Organ Donation Breakthrough Collaborative. Massie et al. (27) recently reported development of a regression model based on donor characteristics to help identify and flag marginal deceased donor kidneys likely to be discarded or delayed beyond 36 h of CIT. The authors suggest that early identification of these ‘hard to place’ kidneys and expedited allocation via an alternative system to direct them to centers most likely to use them based on prior acceptance patterns would decrease CIT and likely reduce discard of these kidneys where under the current system CIT was prolonged to the point of rendering the kidney unacceptable for transplant (27). Alternatively, with free access to data on DSA and regional variation regarding ECD utilization and waiting times to transplant, motivated patients may exercise the option to seek listing at centers providing the best opportunities for expeditious transplant.
Regulation and Reimbursement
The apparent conflict between expectation for an organ procurement organization (OPO) to maximize donor yield, or number of organs transplanted per donor (OTPD), and a transplant center to optimize patient outcomes is particularly evident with marginal donors. In light of recent Centers for Medicare and Medicaid (CMS) requirements (28), many centers may be reluctant to use marginal organs as suboptimal outcomes not meeting performance metrics outlined by the OPTN and CMS may put the viability of the program at risk. Also, ECD kidney transplants are associated with higher early hospitalization costs and charges compared to SCD transplants related to increased DGF requiring hemodialysis, longer length of stay and more frequent need for readmission (29). Although ECD transplants impart survival benefit and are cost-effective compared to waiting on dialysis, reimbursement based on a single diagnostic-related group may not be appropriately adjusted for increased resource utilization associated with these transplants. These additional costs must then be absorbed by the transplant center. The Organ Transplantation Breakthrough Collaborative established goals of 3.75 OTPD and 75% conversion rate (ratio of actual donors to identified eligible donors) as measures of performance for each OPO. The OTPD in aggregate has shown a downward trend in recent years in part due to the increased proportion of ECD donors who typically yield a lower OTPD than SCD donors (2009 OPTN/SRTR Annual Report). Efforts of an OPO to meet the OTPD metric would likely require focusing more on “ideal” donors who have a higher potential organ yield as opposed to ECD donors. This could potentially have negative effects on conversion rate and overall numbers of ECD donors actually recovered. Modeling of expected donor yield adjusted to account for donor casemix within a DSA has recently been proposed and may have the salutary effect of reducing disincentives to pursuing less healthy donors including ECDs (30).
Although the number of LDRTs overall appeared to peak at 6647 in 2004, it is encouraging that LDRTs in recipients aged 65 and over continue to increase with the proportion of LDRTs accounted for by this subgroup more than doubling over a decade, reaching 11% in 2008. In comparison, the proportion of LDRTs in recipients under age 50 decreased over this interval. The number of living donors 50–64 per year has continued to grow, reaching 1437 in 2008, accounting for 24.1% of the total. Living kidney donors aged 65 and over, although relatively rare, are steadily increasing and accounted for 1.5% of all living donors in 2008 (2009 OPTN/SRTR Annual Report). A recent metaanalysis reviewing LDRT outcomes for recipients of all ages suggested that transplants from younger donors had overall better outcomes than those from donors aged 60 and older (31). However, a recent review (32) of OPTN/UNOS data on over 7000 LDRTs performed in recipients over age 60 demonstrated allograft survival for kidneys from living donors aged 55–64 was similar to that with younger living donors. Transplants from living donors aged 65 and older showed graft survival similar to SCD and superior to ECD transplants (32). Older living donors are particularly relevant for older recipients, and include siblings and spouses, who in the analysis accounted for more than three-quarters of living donors over age 55 (32). Previously, follow-up of living donor outcomes including that of the elderly has been inconsistently reported. However, an extensive recent review of the OPTN/UNOS data on over 80 000 living donors, including over 3000 who were aged 60 or older (33) reported no significant difference in surgical mortality, defined as death in first 90 days, by donor age. Although the proportion of donors over 50 years nearly doubled over the study period, the death rate did not change over time. Long-term mortality followed up to 12 years stratified by age was similar or lower for live kidney donors compared to matched controls, including donors aged 50–59, and those aged 60 and older (33). The authors concluded that although more adults older than 50 years are currently donating, there is no evidence that these adults are at higher risk for surgical mortality and current screening practices in older living donors appear to be appropriate (33). Transplant centers are more open to considering older living donors now than in the past. Whereas only 27% of programs reported no upper age limit for living donors in 1995, this more than doubled to 59% in 2007 (34). Individuals with isolated medical abnormalities, such as well-controlled hypertension or nephrolithiasis, were more likely to be considered as donors recently, and programs reported more flexibility in applying selection criteria to older as opposed to younger potential donors (34). Analysis considering remaining baseline risk of ESRD suggests that an older donor with an isolated medical abnormality such as well-controlled hypertension may actually have comparable or less risk than a normal healthy younger donor (35).
Relevant Recipient Considerations
The assertion arising from a review of SRTR data (36) that nearly half of patients over age 60 placed on the waiting list in recent years would not be expected to survive long enough to receive a DDRT highlights the poor prognosis of the elderly on dialysis. The potential benefits of an SCD over ECD kidney for older patients are negated when the younger, more ideal organ comes at the expense of additional years on dialysis (37). Considering the unmet need for deceased donor organs as reflected by current waiting times, allocation of ECD kidneys to older recipients relatively soon after listing would seem to optimize resource utilization as well as provide survival benefit over dialysis for this population (37). The relatively tenuous existence of the elderly on dialysis also stresses the importance of listing appropriate candidates expected to live long enough to derive benefits in terms of survival and quality of life. Conversely, patients in those subgroups demonstrated by registry data analysis (38) not to derive survival benefit from ECD kidneys, such as those under age 40 or with relatively short median waiting times, should not be listed for these organs. Inappropriate listing for ECD kidneys is associated with poorer outcomes for those recipients (39) and possibly contributes to the high discard rate of these organs (6).
Considerations for Future Strategies
The greater issues influencing availability of ECD organs and living donor opportunities for the elderly are not new; however, recently proposed kidney allocation concepts challenge transplant professionals to examine them in a new light. As efforts continue to utilize more organs from older donors, shortcomings of the ECD/SCD dichotomy have become apparent. The more granular KDPI, while yet to be prospectively validated, shows potential to better delineate the continuum of donor risk for allocation policy as well as individual patients. A calculator proposed by the KTC comparing relative benefits of waiting for a DDRT with varying KDPI values, receiving a living donor transplant or remaining on dialysis may be a useful tool to help make this information more understandable and clinically relevant for patients and providers. Biopsy results are the most common reason for refusal of donor kidneys, but good data to support this practice are lacking. The absence of registry data on features other than GS further limits the ability to assess usefulness of histopathology in predicting graft outcome. The ESP experience would argue that reasonable outcomes with older donor organs are achievable with more emphasis on decreasing CIT and appropriate recipient selection. In light of the drain on resources, increased CIT, high discard rate and unproven benefit associated with a procurement biopsy, should a “less is more” approach be considered, with more selectivity and discretion regarding when to proceed with biopsy? To continue with heavy reliance on biopsy to make organ acceptance decisions would seem to mandate collecting better data, perhaps starting with a comprehensive uniform reporting system to capture histopathologic findings beyond GS potentially impacting outcome. Overall encouraging outcomes achieved with DKT including recent favorable results with unilateral placement support increasing DKTs to utilize appropriate marginal kidneys that otherwise would be discarded. Association of MP with a lower discard rate, along with substantial recent evidence that MP improves clinical outcomes favor broadened application to safely increase utilization of marginal kidneys. Analysis of USRDS data and outcome-based modeling suggest that MP may be cost effective as well. Understanding of DSA-specific acceptance practices and development of policies to promote efficient sharing of kidneys that would otherwise be discarded may help optimize utility. Disincentives impeding ECD kidney donation and utilization have been identified at both OPO and transplant center levels, taking forms such as OTPD or graft and patient survival performance metrics inadequately adjusted for donor or recipient risk, or reimbursement not in step with increased financial burden associated with ECD organ transplantation. The net impact of disincentives is difficult to quantify. Yet, is it not conceivable that they play a subtle but significant role behind the relatively unchanged rate of deceased donors over age 65 despite an aging population, or persistently high discard rates of ECD kidneys heretofore ascribed to issues of organ quality? Minimizing negative influences of disincentives by appropriate adjustment of performance measures and reimbursement based on donor or recipient risk would likely enhance various organ breakthrough collaborative efforts to increase ECD organ donation and utilization. Living donors up to age 64 appear to provide the best transplant option for patients older than 60 years, and living donors aged 65 and over may represent an important consideration for patients older than 60 years whose only other viable alternative is an ECD kidney. Judicious expansion of the living donor pool to consider more individuals who are older or who may have isolated medical abnormalities appears appropriate.
In light of ongoing disparity between supply and demand for transplantable organs and the increasing proportion of elderly individuals listed, new allocation concepts striving to distribute kidneys in a manner providing better opportunities for all individuals to achieve as much of a normal lifespan as possible may potentially compromise access of seniors to transplantation. The sustained best efforts of the transplant community to understand relevant issues and develop responsive strategies to optimize utilization of available organs and increase living donor opportunities are needed to help elderly ESRD patients continue to enjoy benefits afforded by transplantation.
This work was supported in part by Health Resources and Services Administration contract 234-2005-37011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. The data reported here have been supplied in part by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the US government.
The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.