No Time to Wait

The critical shortage of organs available for transplantation is now well recognized, with individual transplant centers responsible for managing ever-growing lists of patients awaiting an offer for a kidney that will improve their quality of life and survival. What is less known, particularly to patients and the public, is that many centers regularly turn down such offers and this practice is carried out with little scrutiny. From 2007 to 2012, approximately 7 million deceased donor kidney offers were made and only 0.7% were accepted, with 3.2 million organ refusals related to concerns about the quality of the donor organ being offered (1). Kidneys more likely to be turned down are those with higher Kidney Donor Profile Index (KDPI), AKI, or those from older, obese, diabetic, or hepatitis C virus (HCV)-positive donors. Regardless of the reason, approximately 20% of all kidneys up for offer are repeatedly declined and eventually discarded. One of the longer kidney waitlists in history is an unsettlingly contrast to an organ discard rate now at an all-time high.

There are many reasons why a center may choose to pass on a donor kidney that is considered suboptimal. Experience is required to identify patients likely to benefit from such an organ and it takes time to mine the waitlist for a suitable candidate. A pathologist might report histologic findings on the procurement biopsy that are concerning and pump parameters may herald severe injury to the organ. The ensuing delayed graft function in a kidney with acute injury or prolonged cold ischemia time places patients at increased risk for complications, is a burden on hospital resources, and the potential for marginal function beyond 1 or 2 months post-transplant is frustrating for patients and clinicians. Median wait times vary dramatically across regions and centers with more organ availability may not feel pressure to take on these added concerns. Others may feel the risk is too great in the setting of intensifying regulatory focus on publicly reported post-transplant outcomes. Or it might just be the weekend (2).

There is a strong body of evidence showing that many of these individual acts of omission are collectively irresponsible. Procurement biopsies are notoriously misleading and pump parameters lack appropriate validation for relevant outcomes. Selected donor kidneys with acute injury and high terminal creatinine have excellent post-transplant results. A donor kidney classified as increased risk for disease transmission represents far less risk of death compared with dialysis. Many patients have improved survival from a donor kidney with diabetes, obesity, or the highest KDPI decile compared with remaining on the waitlist to receive a better kidney offer. Even a donor kidney with HCV can be transplanted in recipients with or without HCV and effectively treated with direct-acting antiviral therapy (3). Importantly, there is no evidence to suggest suboptimal kidneys end in regulatory trouble for the centers transplanting them.

The inability to effectively differentiate between perceived and actual risk, or at least a willingness to assume some of the latter, has created marked variability in transplant center offer acceptance patterns. Such variability has engendered many important questions. Is every region, organ procurement organization, and transplant center doing their part to ensure optimal utilization of such a precious resource? Is the organ allocation system efficient if only selected centers are consistently accepting suboptimal kidneys? Are current regulatory performance metrics on post-transplant outcomes creating risk aversion and stifling innovation? And is there appropriate transparency in the organ offer process, especially for patients waiting at a center with a conservative phenotype that may affect their wait time?

In this issue of CJASN, Brennan et al. (4) take an important step forward to help answer some of these questions, delineating several variables representing donor characteristics perceived as unfavorable and then evaluating the effect of each variable on the odds of discard among 113,640 kidneys procured from 2010 to 2016. The coefficients obtained from a multivariable logistic regression are then aggregated together to create a weighted donor utilization index, a valuable tool that is applied to different regions and transplant centers to explore variation in utilization of suboptimal organs among 78,812 kidneys transplanted in 182 transplant centers captured by the Scientific Registry of Transplant Recipients.

The authors find significant heterogeneity among transplant centers in the prevalence of donor variables such as cold ischemia time or donor age. Some of these differences might be expected, as one region compared with the next may have access to differing types of donor kidneys. Moreover, some variability between centers may be good; for example, certain programs may be particularly experienced with managing deceased donor kidneys with acute injury. It is also the appeal of creating a weighted donor utilization index as the authors have done, where variability can still exist but can be standardized across regions or centers.

However, some of the differences highlighted by this study are troubling. Donor utilization index varied within a given region, with centers having an index below the 25th percentile and others above the 75th percentile despite access to the same donor pool. Such differences affected wait time, with increasing index associating with the lower 25th percentile wait time for a kidney. There was also correlation between the donor utilization index and the percentage of kidneys imported to a center. Most patients prioritize a shorter wait time in selecting a transplant center (5). Merely reporting a center’s transplantation rate may be misleading and have unintended consequences, as this metric can be influenced by the type of patients waitlisted and could limit access to more vulnerable patients. Tools like the donor utilization index may be more appropriate, helping inform patients whether their center will be repeatedly declining offers to the patients ahead of them or if it will be aggressively importing kidneys to get them transplanted.

The index uses the overall prevalence of risk factors among all kidneys transplanted at a given center and lacks granularity about the types of kidneys that are actually accepted. In this study, the mean prevalence of the majority of high-risk donor characteristics was between 6% and 20%. It is likely that many centers are willing to accept at least one high risk attribute in a deceased-donor kidney but the summation of multiple concerning attributes in a single kidney up for offer leads to decline and discard. Another recent analysis created a model which scored individual kidneys based on a composite of high-risk features, reliably predicting the risk of organ discard or cold ischemia time >36 hours (6). Only 15% of centers transplanted the majority of kidneys with very high scores and approximately 60% of centers never accepted any such offers. This difference in analytical approach may also be why Brennan et al. did not find an association between center volume and a more aggressive transplant center phenotype despite prior evidence to the contrary (7).

The donor utilization index highlights the need for changes that will ensure the best use of the deceased donor kidney pool, improve efficiency within the organ offer system, and safeguard transparency and equity for waitlisted patients. Several solutions have been proposed (8–10). These include reporting pretransplant metrics that evaluate access to transplantation and organ utilization, much like the donor utilization index. Others have advocated for developing a system to fast-track organs to the centers that will use them or for payers to create a tiered payment system for different types of deceased donor kidneys. Many feel the emphasis must shift to the quality of post-transplant care and away from publicly reported post-transplant outcomes that are misleading and deleterious. Finally, there should be a focus around efforts that foster collaboration around best practices, like the Collaborative Innovation and Improvement Network, an initiative that included the Organ Procurement Transplant Network, organ procurement organizations, and over 50 hospitals that provided collaboration and feedback around waitlist management and organ acceptance of high-KDPI kidneys.

Decades ago, there existed a significant “center effect,” with wide variability of post-transplant outcomes among centers. With standardization in training, uniformity in post-transplant management protocols, and adoption of regulatory performance metrics, variability in graft and patient survival has diminished substantially. But Brennan et al. remind us that a center effect still remains. This effect is partially driven by the same regulatory oversight meant to reduce it, only now it affects survival on dialysis rather than post-transplant, as patients wait for offers that may never be accepted.

Disclosures

Dr. Cooper and Dr. Davis have nothing to disclose.