Throughout the world, the need for kidney transplantation far outstrips the supply. Structural inequalities in allocation, risk-averse organ acceptance, poor care coordination, and waitlisting impediments are among the complex issues that hinder access. As part of its comprehensive vision for patient care, Fresenius Medical Care is taking a multifaceted approach to advancing transplantation. This includes a focus on patient care across the entire continuum of kidney disease and the development of novel organ preservation and regeneration technologies to expand the pool of kidneys available for transplant.
It is uncontroversial that for many patients with advanced chronic kidney disease (CKD) and end stage kidney disease (ESKD), transplantation remains a preferred therapy, conferring better quality and longer life for patients compared with other kidney replacement therapies (KRTs), at considerably lower cost. Regnant immunosuppression regimens, conferring excellent long-term graft survival, have changed little over the last two decades.
Persistent challenges facing the global transplant community include impediments to waitlisting, fewer transplants among marginalized populations, barriers to communication, suboptimal care coordination, insufficient development of cost-effective care delivery models, and risk-averse organ acceptance behaviors.1,2,3 The use of novel organ preservation and regeneration technologies to expand the pool of available organs is also needed. Finally, kidney transplantation is only successful if recipients are cared for in a manner that positions them to enjoy many years of graft survival.
Strategies permitting extended patient monitoring and novel therapeutic targets to prolong patient and graft survival are paramount to maximizing the “gift of life.”4 It is no accident that these goals are consonant with Fresenius Medical Care’s vision to provide comprehensive care to patient populations across the entire continuum of kidney disease.
For vulnerable populations in the United States, equitable access to kidney transplantation has remained stagnant for two decades, despite record year-over-year improvements in organ procurement and transplantation, including during the COVID-19 pandemic.5 Insufficient waitlisting rates have led some commentators to recommend an “opt-out” approach to transplant referrals: unless individual patients refuse or have an absolute contraindication, all would be referred for transplant by default.6 Others recommend revisions to an allocation system that currently privileges “preemptive” waiting time. While the revision to this system in 2014 went some distance in reducing unequal rates of deceased donor kidney transplantation in Black Americans, preemptive waiting time is often not available to those who “present late” with ESKD, which in turn may recapitulate structural inequalities in waiting list prioritization.7
Revisions to the kidney allocation system designed to bring precision to assessments of organ quality (in the form of the Kidney Donor Profile Index, or KDPI)—in order to direct high-quality kidneys to young recipients—has not fully ameliorated access disparities.8 Unintentionally, this same scoring system often resulted in “high” KDPI kidneys (suggesting a worse long-term outcome) being discarded more frequently compared to organ acceptance trends before the implementation of the KDPI system.9 A study comparing organ acceptance and discard behaviors in the US and France showed that >17,000 kidneys discarded in the US would likely have been transplanted in the French transplant system.10 Even an ostensibly positive development like the elimination of the three-year limit on Medicare coverage for 80 percent of the expenses of immunosuppression medications will still require recipients to find funding for the remaining 20 percent of the cost.
A recent shift toward a “geographic” allocation of kidneys to recipients within 250 nautical miles of the donor hospital may abate long-standing disparities in median waiting times for kidneys in areas of high population density. In essence, however, this solution is likely to extend median waiting times for all patients and increase the costs of organ procurement by causing more kidneys to be shipped longer distances. Whether the new allocation system effectively alleviates the structural inequalities in access to transplantation, or simply extends the waiting time for all candidates on the list without alleviating access disparities, remains to be seen.
Novel allocation schemata will only be of theoretical interest for the far too many patients who remain on the outside of the waitlisting system looking in. In many countries, living donor kidney transplantation is a mainstay, reﬂecting a limited infrastructure to accommodate organ procurement from deceased donors, often compounded by the absence (or relatively recent enactment) of a legal and policy framework governing organ procurement and allocation. For example, India passed the Transplantation of Human Organs Act in 1994, a response in part to reports of India serving as a global nidus of organ trafficking. Twenty-five years later, nearly 90 percent of all kidneys and almost three-quarters of transplanted livers in India are still procured from living donors. For the most part, organ transplantation is only available to those in the private healthcare system, underscoring that policy reforms are necessary but not sufficient conditions for success.11
The need for kidney transplantation far outstrips the available supply around the world. For patients enduring the worst vicissitudes of the social determinants of health, addressing insecurities in food, water, housing, and transportation, as well as bridging the digital divide, is far more salient than novel organ preservation technologies or organ allocation debates. Australia boasts an impressive five year patient and graft survival rate, which has been attributed to multidisciplinary teams devoted to long-term care, a robust single-payor system, and an outcomes-tracking system that feeds back to transplant programs; however, even Australia struggles to equitably serve the Aboriginal population with ESKD.12,13
It is too heavy a lift to rely on care coordination to address inadequate social infrastructure, but a reasonable place to begin is to design, scale, and implement technologies to enable virtual assessments and patient tracking technologies that meet and provide clinical services to patients “where they live” rather than “where the doctors work.” The value of expanding “telemedicine” capabilities and artificial intelligence tracking tools is in advancing primary and secondary efforts to delay the progression of CKD, provide early-warning systems for clinical deterioration, and provide an efficient means of tracking entire populations of patients who are hoping to keep their transplant for as long as possible.
To improve access to transplantation, population-level health management and patient tracking tools can identify clinically appropriate candidates early, provide comprehensive education about the benefits of transplantation, target subpopulations for assistance in identifying living donor candidates, schedule needed testing in a rational manner that avoids unneeded repetition and redundancy, provide an efficient means of tracking the progress and ongoing clinical suitability of waitlisted patients, and ensure that no viable candidates “get lost” in the evaluation process, as too many often do. The key to ameliorating access disparities is to ensure no transplant candidate is consigned to the shadows. As with all such technologies, implementation will need to be guided and checked by an ethical framework that safeguards autonomy and privacy and foregrounds close attention to patients’ treatment preferences, efforts that will inexorably be a process and not a single event.14
As a recent “road map” for improvement published by the European Kidney Health Alliance showed, ample opportunities remain to improve organ procurement rates between and within countries (Figure 1).15 The COVID-19 pandemic exposed the resilience of organ procurement regimens in some parts of the world and the vulnerability of many others. Conspicuously, after a brief pause in March to April 2020, organ procurement rates in the US rebounded to record levels by the end of 2020. In France and elsewhere, the pandemic had a catastrophic effect on organ procurement rates.16 It is believed that similar depressions in organ procurement have transpired globally, and a systematic accounting of this trend across multiple countries is a focus of ongoing study.17 Learning the lessons of how the US managed to recover and remain successful in procuring organs during the pandemic will be instructive for organ procurement systems globally. One approach is to procure organs and tissues outside the traditional hospital system, increasing capacity for needed intensive care unit beds and operating rooms.18,19 This could prove important not only for future pandemics, but for the future of organ and tissue procurement around the world.
Learning how to successfully expand access to organ transplantation will be for naught unless more organs are procured. In the US, a 15-year regulatory regime requiring transplant centers to achieve a high threshold for patient and graft survival under threat of decertification from Medicare finally came to an end. This regulatory policy likely led to demonstrable risk aversion regarding candidate listing practices and organ acceptance behaviors, possibly contributing to a durable 20 percent rate of organ discard in the country.20 While not all the discarded kidneys were likely viable, prudent and targeted regulatory reform is needed to encourage transplant surgeons to accept and transplant ostensibly “higher risk” kidneys without risking regulatory or financial jeopardy.
So-called “presumed consent” or “opt-out” policies in Europe, in which consent to organ procurement after brain death is “presumed” for policy purposes, are variably defined and enforced, and have not been shown to improve organ procurement rates compared to the traditional “opt-in” consent model extant in the US.21
One promising avenue is to build on the success of the European Union’s European Senior Program (ESP), which improved access to transplantation for elderly recipients by explicitly allocating kidneys from older donors (which might otherwise have been discarded) to them.22 While expanding the organ pool is an important strategy, it will not be a wholesale panacea: a recent analysis from Europe suggests that extending elderly donors after circulatory death may not routinely confer survival versus maintenance dialysis.23
In addition, identifying key demographic differences in high-KDPI kidneys will be key to learning the right lessons about more aggressive organ procurement. A recent retrospective review of utilization of and outcomes from using high-KDPI kidneys in the UK showed that high-KDPI scores in UK donors were often driven more by advanced age, rather than the combination of advanced age and comorbidities such as hypertension and diabetes.24 Given the limitations of the KDPI score as a predictive tool (the KDPI only has a c-statistic of 0.6 for predicting graft survival), the need for more sophisticated prognostic tools to make distinctions between subcategories of “high risk” kidneys is urgent.25
Improving access is also for naught without longevity. In the US, a conﬂagration of quality metrics focused on one-year outcomes, a culturally bound sharp separation of duties between transplant centers and general nephrologists, and a payment model that rewards procedures more than longitudinal care all conspire to make the long-term care of transplant recipients no one’s dedicated responsibility. Given a recent analysis that showed the burden of premature graft failure in the US in 2017 resulted in $1.37 billion of additional costs and a reduction of nearly 30,000 additional quality-of-life years, implementing population health interventions to extend patient and graft survival harmonizes good patient care with return on public investment.26
Happily, there are new potential therapeutic targets for extending allograft survival, including some early data suggesting that sodium glucose co-transporter 2 inhibitors (SGLT-2i) may be of benefit in transplanted patients.27 Providing this end-to-end care for patients across the continuum is integral to the future of integrated patient care models that will be pioneered by Fresenius Medical Care.
To improve access and increase the total number of kidney transplants performed, and to improve access to kidney transplantation for patients around the world, Dr. Hippen and his team will focus on: