… Life Lies Waiting


Managing the kidney transplant waiting list for candidates awaiting organs from deceased donors has reached a serious state. In April 2003, the waiting list for kidney transplantation from deceased donors exceeded 54 000 candidates (1). It will get much worse. The number of kidney transplants from deceased donors increases by an average of only 1.8% per year; the number of patients added to the waiting list increases at a rate of 11% per year (2). The disparity prolongs waiting times. In 2001, 40% of registrants waited longer than 2 years, and 17% waited 3–5 years (2). Importantly, the increase in waiting time is not shared equally among ethnic groups. For Caucasian patients listed in 1997 (the most recent accurate data period) the time to transplant was 675 days and for African Americans 1603 days (2). There are also wide disparities regarding the likelihood of transplantation by level of presensitization. Unfortunately, women and African Americans are more likely to be sensitized than men and members of other racial ethnic groups. Prolonged waiting time affects quality of life and diminishes the efficacy of the life-saving nature of renal transplantation when it is finally performed (3).

In this issue of the American Journal of Transplantation, Dr Gaston and his colleagues have reported on the March 2002 Philadelphia, PA conference to review national policies affecting the waiting list for kidney transplantation (4). This conference was complementary to the March 2001, Crystal City, VA conference sponsored by the AST and ASTS that produced the ‘Report of the Crystal Meeting to Maximize the Use of Organs Recovered from the Cadaver Donor’, recently published in the American Journal of Transplantation (5). The current conference was well organized to systematically identify problems and to suggest reasonable remedies in managing the enlarging waiting list (5). The report addresses many of the pertinent issues impacting management of the waiting list. Foremost is its focus on fair and equitable access to kidney transplantation for all patients with end-stage renal disease. The report is very elegant in its efficiency in delineating the barriers in access to transplantation.

Assigning priority on the list over and above waiting time is becoming more and more controversial. The report addresses the ethical dilemma posed when kidneys are allocated in the context of the equity/utility paradigm. The main issue of utility relates to the benefits of HLA matching. HLA matching as a method of allocating kidneys from deceased donors under the utility pretext (i.e. it results in clinically significantly improved outcomes) is being held up to tighter scrutiny. There is a difference in 5-year kidney allograft survival from recipients of zero mismatch HLA cadaveric kidneys compared to the other groups when examining a cohort of transplants performed in 1995–96 (the most recent data available) (1). What is unclear is whether the difference in outcome is directly related to immunologic causes of graft loss or other causes (e.g. death with function). A plausible alternative possibility is that the improvement in late outcomes reflects a difference (less) in calcineurin inhibitor exposure in recipients of 0 antigen mismatched kidney allografts. Will application of the newer maintenance immunosuppressive agents that began being incorporated in treatment protocols shortly after that time narrow the difference? Time will tell.

The use of HLA matching to allocate kidneys diverts organs from candidates who have prolonged waiting periods; an inequity that is disproportionately borne by African American recipients. Therefore, any allocation system that uses HLA matching has inherent ethnic bias. To this end, the conference proposed an allocation point change that has recently been adopted and incorporated into UNOS guidelines. However, points are still being offered for the DR mismatch combination, and there is still mandatory national sharing of zero ABDR mismatched organs.

Eliminating nearly every variable except waiting time to allocate kidneys will also ensure patient readiness for kidney transplantation. Maintaining and monitoring the health status of patients once they are on the list is only practical if one can predict within a defined short (i.e. 6 months) period when they are likely to receive a transplant. Then the patient can be evaluated at the transplant center at a reasonable time prior to transplantation for optimal medical preparation. This is another HLA-independent reason why recipients of living-donor kidneys do well post transplant. What has not been quantified is the extent to which kidney transplant outcome from deceased donors is adversely affected by an inefficient system of ensuring patient readiness.

An interesting local solution to this issue has been in place for nearly a decade in Northern California served by the California Donor Network (6). Local kidneys from deceased donors are not allocated according to HLA matching. This may be a reasonable system of allocation at select centers. For example, the University of California at San Francisco (UCSF) Medical Center has over 3000 individuals awaiting cadaveric kidney transplantation. It is an impossibility to expect that all patients will be ready at all times to receive a cadaveric kidney. That is what is currently required when HLA matching affects allocation. How well do adult recipients of kidneys from deceased donors do at UCSF? Data from the Scientific Registry of Transplant Recipients (SRTR) recently showed UCSF to be one of only six US transplant centers in which adult recipients of kidneys from deceased donors enjoy 3-year allograft survival rates statistically significantly higher than calculated expected results (7). They also found that this allocation method resulted in a more equitable distribution of organs among different ethnicities based on equalization of waiting time.

Center by center, we now know that we do not stand alone in trying to solve these problems. New paradigms of improving access to kidney transplantation need exploration based on the variables so effectively reported by Gaston et al. One size (national policy) may not necessarily fit all equally well. The powerful data collection and analyses systems that have been established (e.g. SRTR) are very useful to guide national policy, but should also be more heavily utilized to guide local allocation variances in smaller districts. It is now possible to customize the weight of the allocation variables through data analyses tailored to consider the demographic characteristics for a specific geographic region in the US to better balance the equity/utility discord.

The consequences of patients not being ready in a timely manner are likely to be more profound than we are willing to admit. Open challenge to allocating kidneys for adult transplantation based on systems that dilute the importance of waiting time is constructive activity. The medical culture and politics of waiting-list management are vastly understudied; that is why this report is so important. It challenges transplant professionals, and others, to enact practices that improve the well-being of the community – and to do so without ethnic or gender bias. This report is an important contribution, illuminating on a national scale what we feel are very difficult problems to solve locally – managing an increasingly large waiting list, removing ethnic bias, and improving outcomes. Much of what currently is must be actively changed. In the meantime, life lies waiting.