An Emerging Population: Kidney Transplant Candidates Who Are Placed on the Waiting List after Liver, Heart, and Lung Transplantation

Discussion

The number of candidates who are placed on the waiting list for KTx after a previous nonrenal transplant is growing significantly. NRTx candidates are listed before dialysis initiation more frequently than non-NRTx recipients and receive similar quality organs. Our data also point to a relative underuse of ECD KTx, and listing of NRTx candidates who have a poor prognosis on the waiting list particularly benefit from reduced waiting time.

NRTx candidates are also listed before dialysis initiation more frequently than those with KTx alone and receive organs of similar quality to those who receive KTx alone. It was shown previously that preemptive KTx confers a significant survival benefit over waiting for a KTx on dialysis (5,6); however, that preemptive renal transplantation is underused in the ESRD population at large but relatively more frequently used in the NRTx candidate pool raises serious concerns about the disparity in access in these two patient groups to optimal medical practices that could optimize survival. Although it is not possible to demonstrate that this is indeed the case, in our retrospective study, the more frequent predialysis listing of NRTx recipients for KTx likely reflects greater access of NRTx patients to close medical follow-up by transplant physicians. This finding further raises questions about the advantages to patients with physician advocacy on the one hand and the limitations that need to be in place to ensure fair and equitable access to optimal medical practices to all those in need on the other hand. It has been pointed out that it is important to consider the mortality risk of the thoracic transplant recipient before considering them for a subsequent KTx, the rationale being that kidneys should be offered to those who are likely to accrue the greatest mortality benefit (7). More recently, it was shown that preemptive transplants confer benefit to KTx candidates who were heart transplant recipients (8). Such a practice, in addition to careful patient selection, would certainly help to minimize waiting times given the poor survival of the NRTx recipient/KTx candidate on the waiting list (9,10).

Importantly, organ allocation systems for liver, lung, and heart transplants emphasize disease severity over wait time. In the case of KTx, disease severity is not accounted for in the deceased-donor allocation system. As such, an adult KTx candidate with poor expected survival on the waiting list could wait for years and could die on the waiting list before receiving a kidney offer (11). ECD kidneys may offer a survival benefit by helping to minimize waiting time, such as has been noted in older patients, patients with diabetes, and KTx candidates who reside in areas with long waiting times (12,13). Our results show, however, that despite a markedly higher mortality rate on the waiting list, NRTx recipients are not listed more frequently for ECD KTx, a strategy that could minimize deleterious effects of waiting time. This relative underuse of ECD KTx listing among NRTx recipients could thus represent a lost opportunity with regard to minimizing waiting time. It has also been shown that transplant center practices could have a significant impact on the effectiveness of ECD listing and use with a view to reducing waiting times (14). Given these considerations, although targeted listing for and transplantation of ECDs in NRTx recipients may be a viable option to reduce waiting time, as has been shown recently in the specific instance of candidates who received a previous heart transplant, the actual effectiveness of this strategy will likely be influenced by (1) the choice of the NRTx patient (and his or her physicians) to consider and/or accept ECD listing and (2) the transplant center's effectiveness in reducing waiting times by judicious use of ECD transplantation. In this regard, patients with NRTx could well benefit by being listed at a center that is known to have high transplant rates for those who are listed for ECD kidneys (8,14). It should be noted, however, that our findings derive from a retrospective analysis and only carefully designed prospective studies can validate some of our proposed measures to mitigate the deleterious effects of waiting time on NRTx recipient/KTx candidate survival.

In recent years there has also been significant growth in the number of KTxs performed simultaneously with the NRTx, particularly in liver transplantation (15). By design, MELD-based allocation for liver transplantation prioritizes liver transplantation in patients with pre–liver transplantation renal insufficiency (15,16). As such, the MELD-based liver allocation system could possibly select out patients who have pre–liver transplantation renal insufficiency and were destined for ESRD. A single-center study (17) noted no difference in the incidence of CKD in the pre- and post-MELD eras in liver transplant recipients; however, that study was conducted in a region with one of the lowest MELD scores in the country and/or inadequate statistical power. As noted in our study, that KTx listings after a previous liver transplant have significantly increased in the MELD era suggests that the incidence of chronic kidney disease (CKD) in patients who receive a liver transplant alone and progresses to ESRD may in fact be increasing (18).

Our analysis focuses on the NRTx recipient population as a whole, who are now candidates for KTxs. As shown in our analyses, these patients are a growing segment of the candidate pool for renal transplantation. These patients do have a substantial burden of mortality on the waiting list, and appropriate use of renal transplants in this population, whether living or deceased donor, raises several medical and ethical concerns. For example, it remains to be determined whether similar efforts by transplant centers are exercised in securing a live-donor kidney for an NRTx candidate as are usually used to secure a live donor for a kidney-only transplant. The higher frequency of preemptive listings of NRTx recipient/KTx candidates could reflect greater access to transplant care on the basis of past familiarity with the transplant process. The appropriateness of preemptive listing of an NRTx recipient who needs a transplant, however, is understandably justified on the basis of both excess mortality on the waiting list and the net benefit conferred by and expected of successful KTx. The actual number of years of additional life conferred by a renal transplant is greatest for those who receive a KTx alone as opposed to a KTx after NRTx, a phenomenon reflective of the lower overall survival in NRTx recipients compared overall with solitary KTxs. Our findings then prompt the question of maintaining equitable access to renal transplantation to the kidney-alone candidate who is on the waiting list and whose access to a kidney is primarily dictated by waiting list time.

In light of our discussion, we submit that the NRTx recipient has two chances to obtain a KTx, simultaneously with the NRTx or subsequently with the onset of renal failure after NRTx. Whereas the candidate for a KTx alone does not have the biological advantage of receiving the NRTx on the basis of disease severity and has to wait for a transplant, that latter process is associated with an annual mortality of at least 6%. In addition, recipients of simultaneous liver and kidney transplants receive organs from a greater number of standard-criteria donors compared with kidney-only candidates. Of greater concern is that preemptive renal transplants, widely known to confer a survival advantage to the patient with ESRD over placement on the waiting list and receiving dialysis, are offered less frequently than is in the case of the NRTx candidates. Furthermore, the overall patient and graft survival in the NRTx pool is significantly lower than that for those who receive KTx alone (Figure 3). The use of ECD kidneys may provide a means to minimize waiting times in such patients, as has been advocated for other patient groups with poor expected survival on the waiting list or long expected regional waiting times.

That kidney transplant listings are increasing in the NRTx population is perhaps an indication of (1) the growing burden of CKD in this population and (2) the overall growth in NRTx numbers. Given these complexities, the medical care of NRTx recipients may demand the structured involvement of physicians who are skilled in the organ-specific care of NRTx recipients as well as immunosuppression, care of CKD, and ESRD planning through all phases of transplantation.