Position Statement

A Roadmap for Innovation to Advance Transplant Access

and Outcomes: A Position Statement From the National
Kidney Foundation
Krista L. Lentine, Stephen Pastan, Sumit Mohan, Peter P. Reese, Alan Leichtman, Francis L. Delmonico,
Gabriel M. Danovitch, Christian P. Larsen, Lyndsay Harshman, Alexander Wiseman, Holly J. Kramer,
Joseph Vassalotti, Jessica Joseph, Kevin Longino, Matthew Cooper,* and David A. Axelrod,* on behalf of the
National Kidney Foundation

Over the past 65 years, kidney transplantation has evolved into the optimal treatment for patients with kidney Complete author and article
failure, dramatically reducing suffering through improved survival and quality of life. However, access to trans- information provided before
references.
plant is still limited by organ supply, opportunities for transplant are inequitably distributed, and lifelong transplant
survival remains elusive. To address these persistent needs, the National Kidney Foundation convened an expert Correspondence to
panel to define an agenda for future research. The key priorities identified by the panel center on the needs to K.L. Lentine (krista.lentine@
health.slu.edu)
develop and evaluate strategies to expand living donation, improve waitlist management and transplant readi-
ness, maximize use of available deceased donor organs, and extend allograft longevity. Strategies targeting the *M.C. and D.A.A. contributed
critical goal of decreasing organ discard that warrant research investment include educating patients and cli- equally to this work.
nicians about potential benefits of accepting nonstandard organs, use of novel organ assessment technologies Am J Kidney Dis.
and real-time decision support, and approaches to preserve and resuscitate allografts before implantation. The 78(3):319-332. Published
development of personalized strategies to reduce the burden of lifelong immunosuppression and support “one online July 27, 2021.
transplant for life” was also identified as a vital priority. The panel noted the specific goal of improving transplant doi: 10.1053/
access and graft survival for children with kidney failure. This ambitious agenda will focus research investment to j.ajkd.2021.05.007
promote greater equity and efficiency in access to transplantation, and help sustain long-term benefits of the gift © 2021 by the National
of life for more patients in need. Kidney Foundation, Inc.

As this article reflects the official position of the National

Kidney Foundation (NKF) and because it was reviewed and
approved by NKF, it was not peer reviewed by AJKD. This
article was prepared by a work group comprising the authors
and chaired by Dr Krista Lentine. It was reviewed and
approved by the NKF Scientific Advisory Board and the NKF
Executive Committee.
Introduction
Kidney transplantation—and especially living-donor kid-
ney transplantation (LDKT)—offers patients with kidney
failure the best chance for long-term survival and
improved quality of life, at the lowest costs to the health
care system.1,2 There have been many positive trends in
kidney transplantation in recent years, including a pro-
gressive rise in rates of deceased donor kidney trans-
plantation and improvements in short- and longer-term
allograft survival.3 However, the field continues to face
important challenges. The vast majority of the more than
700,000 persons in the United States with kidney failure
will not have an opportunity to receive a transplant due to
limitations in organ supply. Those who receive a transplant
often ultimately return to dialysis due to limited long-term
graft survival resulting from chronic allograft nephropathy,
recurrence of native disease, medication nonadherence, or
other causes.2,4 Efforts to expand the deceased donor organ
supply have increased the use of kidneys from older and
other nonstandard donors to some extent, yet many
potentially transplantable organs continue to go unused.
Decisions not to use recovered organs are generally
attributed to kidney quality, but are, in fact, multifactorial,
reflecting opinions about transplant benefit, cost, program
regulatory risk, and logistical complexity, not all of which
are supported by evidence-based assessments.
The population in need of transplant is increasingly
complex and diverse, including a higher prevalence of
older patients, as well as individuals with comorbidities
(eg, obesity, diabetes mellitus, cardiac disease) and of non-
White race or ethnicity (Fig 1).2 Furthermore, rates of
LDKT in adults and children have generally stagnated while
racial disparities in LDKT access persist or worsen.5 The
need to increase access to kidney transplantation received
unprecedented support from the federal government in the
July 2019 Advancing American Kidney Health executive
order, which articulated goals for increasing the initiation
of kidney replacement therapy through transplant and
substantially increasing the number of kidneys available for
transplant by 2030.6 These efforts were initially hampered
by the global novel coronavirus disease 2019 (COVID-19)
pandemic, although rates of both deceased donor trans-
plantation and LDKT subsequently recovered to prepan-
demic levels.7,8,9
To assess the knowledge gaps amenable to research
support aimed at advancing the practice and outcomes of
kidney transplantation, the National Kidney Foundation
(NKF) convened an expert panel. The panel was charged
with developing a research agenda to facilitate access to
kidney transplantation for all patients who can benefit,

AJKD Vol 78 | Iss 3 | September 2021 319

 Lentine et al

A Candidate Age at Listing, by Listing Years B Candidate Race/Ethnicity, by Listing Years

100% 100%

80% 80%

60% 60%

40% 40%

20% 20%

0% 0%
2000-2005 2006-2010 2011-2016 2017-2020 2000-2005 2006-2010 2011-2016 2017-2020
<=18 19 to 30 31 to 44 45 to 59 >=60 White Black Hispanic Other

C Candidate BMI at Listing, by Listing Years D Candidate Cause of Kidney Failure, by Listing Years
100% 100%

80% 80%

60% 60%

40% 40%

20% 20%

0% 0%
2000-2005 2006-2010 2011-2016 2017-2020 2000-2005 2006-2010 2011-2016 2017-2020
<18.5 18.5 to <25 25 to <30 30 to <35 >=35 Hypertension Diabetes mellitus
Glomerulonephritis Polycystic kidney disease
Other/Unknown

Figure 1. Changing characteristics of the US kidney transplant waiting list. Prepared from Scientific Registry of Transplant Recip-
ients data, 2010-2020. Age is shown in years; body mass index (BMI) is shown in kg/m2.

support the goal of “one transplant for life” for organ
recipients, and reduce/eliminate racial and ethnic dis-
parities in transplant access and outcomes. Participants
included nephrologists, surgeons, organ procurement
organization (OPO) leaders, NKF leadership, patients, and
other interested parties. Consensus-building was con-
ducted through email, conference calls, and an in-person
roundtable meeting December 13, 2019, in New York
City. Through facilitated discussions, the panel developed 7
priorities for research innovations. The in-person meeting
occurred shortly before the COVID-19 pandemic, and
recommendations have been updated in the context of the
latest challenges facing the field.
Priorities for Research Innovation
Priority 1: Expand Opportunities for Safe Living
Donation and Access to LDKT
Living kidney donors can be related, unrelated, nondi-
rected, or participants in donor exchange (kidney paired
donation [KPD]) programs. Benefits of LDKT over
deceased donor kidney transplantation include faster
access to transplant and superior patient and allograft
survival at the lowest cost to the health care system.1 In
the United States, the number of LDKT declined from
6,000 in 2004 to approximately 5,500 per year through
20173; 2018-2019 showed a promising trend of

320 AJKD Vol 78 | Iss 3 | September 2021

Lentine et al
1200
Paired Donation
1000
Counts of LDKT 800
600
400
200
0
'00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12 '13 '14 '15 '16 '17 '18 '19
Figure 2. Counts of kidney paired donation and nondirected donation over time. Prepared from Scientific Registry of Transplant Re-
cipients data, 2000-2019. Abbreviation: LDKT, living donor kidney transplant.
an increase to nearly 6,900 LDKT, although growth was
stalled in 2020 by the temporary disruption of nearly all
LDKT activity at the start of the COVID-19 pandemic.9
Barriers to LDKT include the transplant candidate’s
ability to identify a willing and appropriate donor,
concerns for donor health and follow-up, and economic
barriers to donation including out-of-pocket expenses
and lost wages.10
Development of KPD programs for patients with willing
but biologically incompatible donors has been an impor-
tant advance in expanding opportunities for LDKT.11 Using
algorithms to exchange kidneys among 2 or more
donor–recipient pairs, KPD programs create compatible
combinations that address blood group and donor-specific
alloreactivity incompatibilities. Nondirected donors (ie,
donors who do not have an identified recipient) provide
the unique potential to expand the donor pool through
chains of kidney exchanges.12 KPD is the fastest growing
LDKT modality and currently comprises approximately
16% of LDKT per year (Fig 2).3 However, KPD is under-
used due to cost, complexity, patient and physician
acceptance, and degree of allosensitization. If all centers
used KPD at the rate of high-performing centers, it is
estimated that another 1,000 transplants could be per-
formed annually.13 Entering compatible pairs into KPD is
another suggestion to further increase the pool of potential
matches and provide benefits such as better balance
in kidney mass/function of exchanged donors, and
improved degree of tissue matching (ie, reduced eplet
mismatches) to lower long-term rejection risk.14 Addi-
tional innovations in some KPD programs include
“advanced donation,” wherein a donor gives to the KPD
pool in exchange for a voucher for a donation to their
intended recipient at a later time if and when needed,
designed to overcome “chronological incompatibility.”15
AJKD Vol 78 | Iss 3 | September 2021
Non-Directed Donation
Year
Other strategies for increasing LDKT include educa-
tional interventions, public campaigns, evaluation effi-
ciencies, and donor cost mitigation efforts.16 In a scoping
review, Barnieh et al identified 26 studies reporting stra-
tegies to increase LDKT.17 Patient education was the only
strategy empirically assessed by randomized clinical trials,
and only 2 (involving home-based education of transplant
candidates and members of their social network) found
significant increases in LDKT and living donor evalua-
tions.18,19 Despite the urgent need to increase access to
LDKT, only 6 quasi-experimental and 13 observational
studies assessed diverse strategies such as education, organ
donation awareness campaigns, advocacy (training a
donor champion), efficiency (web-based screening, crea-
tion of interdisciplinary teams), removal of disincentives
(leave policies, tax benefits), and institution of KPD pro-
grams. The only quasi-experimental study in the system-
atic review that identified an increase in LDKT was a
structured educational program for potential recipients and
their families.20 Further, well-designed evaluation trials are
needed to identify successful interventions for increasing
LDKT, especially for populations with reduced LDKT
access.
Recently, a growing body of evidence has quantified
and continues to improve estimates of the potential risks of
living donation for donors, such as a tool using donor
candidate demographic and health characteristics to esti-
mate (in the absence of donation) the 15-year and lifetime
risk of kidney failure (https://www.ckdpc.org/tools.
html).21 Additional research is required to validate and
increase the precision of such tools22 and to incorporate
emerging risk factors (eg, apolipoprotein L1 [APOL1] as a
genetic risk marker).23 Unfortunately, methods for effec-
tively communicating risk information to potential donors
have been poorly studied. Even though interventions to
321

Educaon & Outreach
Target audiences
• Paents with kidney failure
• Potenal living donors
• Social networks
• General public
Research needed to opmize
• Frequency
• Content
• Delivery modalies
Evaluaon & Process Efficiency
Complex donor evaluaon process
• Delays may discourage donors
• Delays may lead to recipient
starng dialysis before transplant
Research needs
• Develop standards to address
modifiable process delays
• Remove logiscal barriers to KPD
parcipaon
Figure 3. Focal points for future research to define effective strategies for increasing access to living donor kidney transplant.
Adapted from Lentine and Mandelbrot10 with permission of the American Society of Nephrology (ASN). Original content ©2017
ASN. Abbreviation: KPD, kidney paired donation.
improve transparent communication of risks and long-
term donor safety are not primarily directed at increasing
LDKT, these efforts are critical to sustaining trust in LDKT
and for informing evidence-based education and donor
selection practices.24 Efforts to develop registries tracking
long-term living donor outcomes in diverse populations
are also needed.25,26
Attention to improving equity in LDKT access for Black,
Hispanic, and other non-White patients, as well as those
with lower levels of socioeconomic status and health lit-
eracy, is a vital priority.27 Although removing financial
disincentives is broadly accepted as necessary to improve
equity in donation and access to LDKT, evidence demon-
strating the impact of programs targeting financial
neutrality on donation rates has been limited to date.28
Addressing financial burdens to donors is particularly vi-
tal, as a pandemic-related recession may challenge op-
portunities for living donation beyond the end of the
public health emergency. Technology may enable efficient
education delivery, but evidence is needed to determine if
e-learning, telehealth, or telephone-based LDKT education
programs are as effective as in-person education. Further
research is also needed to improve the efficiency of donor
evaluations and to generate evidence-based standards
to address modifiable process delays.29,30 Dissemination
studies are also necessary to assess whether effects persist
322
Lentine et al
Removal of Disincenves
Uncompensated costs for donors
• Travel
• Medicaons
• Lost me from work
• Dependent Care
Research needs
• Develop and assess mechanisms
for achieving cost neutrality
Improving Safety & Defensibility
of Donor Selecon
Transparency
• Incomplete risk assessment and
disclosure may reduce trust of the
public and potenal donors
Research needed to opmize
• Scope and precision of long-term
risk predicon
• Methods for risk communicaon
when programs are scaled and to identify unexpected
barriers that may arise with wider implementation.
Recommendations
The panel agreed with recent suggestions that high-priority
research to increase access to LDKT should include devel-
oping, accessing and expanding strategies (Fig 3)10 to:
• Improve education and outreach to kidney patients about
effective strategies for potential donor identification;
• Reduce financial disincentives to donation;
• Improve the efficiency of donor evaluations and predo-
nation processes, with particular attention to removing
disincentives and logistical barriers to KPD participation
for programs and patients;
• Optimize donor risk assessment and long-term follow-
up; and
• Identify and implement methods to improve risk
communication, transparency, and shared decision-
making in the donor candidate evaluation.
Priority 2: Improve Waitlist Access, Management,
and Pretransplant Readiness
Among the nearly 95,000 patients waiting for kidney or
combined kidney/pancreas transplant in March 2021, 43%
had an inactive status.31 Thus, despite being approved for,
AJKD Vol 78 | Iss 3 | September 2021
Lentine et al
and presumably in need of, a kidney transplant, these
patients will not appear on a match run for organ offers.
Patients are inactive for a variety of reasons (eg, current
medical illness, psychosocial barriers, preserved kidney
function that meets listing criteria but does not warrant
kidney replacement therapy). Patients who are initially
listed as inactive have twice the risk of waitlist mortality
and 32% lower rates of eventual transplantation than pa-
tients initially listed as active.32 The prevalence of inactive
status on the waiting list is higher among racial and ethnic
minority populations. One study of national US waitlist
records found that, among patients who were inactive,
Black patients were 19% less likely to convert to active
status and Hispanic patients were 27% less likely than their
White counterparts.33 This disparity directly impacts access
to transplantation and overall mortality.
The process of referral and evaluation for transplant is
complex and often difficult to navigate. Patients
must complete rigorous testing and examinations to ensure
that there are no medical or surgical contraindications to
transplantation. Racial and socioeconomic disparities in
completing the evaluation are well documented and persist
even after controlling for other social determinants of
health.34 Time- and resource-intensive interventions (eg,
patient navigators, individually tailored educational pro-
grams, coaching) have increased the proportion of patients
who are successfully waitlisted in single-center trials.35
The panel agreed that there is an urgent need to
develop and disseminate best practices for transplant
centers to reduce inactivation status on their waiting lists.
Kataria et al reported that frequent programmatic review
allowed 18% of inactive patients to be made active,
although this also led to delisting of 40% of inactive pa-
tients at their center.36 The panel considered research
opportunities that target specific barriers with effective in-
terventions. For example, patients with a body mass index
exceeding center acceptance thresholds can be referred for
nutritional interventions and possible bariatric surgery.37,38
Bariatric procedures have been shown to achieve durable
weight loss and increase transplant access for appropriate
candidates.39,40 A systematic review/meta-analysis including
288 patients with advanced kidney disease demonstrated
that 50% lost sufficient weight for transplant listing.40
However, access to bariatric surgery remains limited for
the population with advanced kidney disease.
Frailty is another frequent barrier to kidney trans-
plantation, such that frail patients are half as likely as
nonfrail counterparts to be listed for transplant.41-43
Among those who are listed and receive transplants, the
approximately 20% of recipients who are determined to
be frail at transplant are twice as likely to die after
transplant as nonfrail recipients. Current data suggest that
objective frailty scoring systems, rather than subjective
physician assessments, are more accurate and should be
used at the time of evaluation.42,43 For frail patients, a
structured program of “prehabilitation” and physical
therapy may help improve physical functioning
AJKD Vol 78 | Iss 3 | September 2021
sufficiently to allow transplant. Further work is needed to
identify the best assessment tools and successful in-
terventions to facilitate access to transplantation and
improve posttransplant outcomes for frail kidney patients.
The COVID-19 pandemic created a new emphasis on
remote assessments, including of candidate physical
functioning at evaluation and while awaiting a transplant
offer.9
Recommendations
• Optimize strategies to eliminate barriers to waitlist
acceptance, including management of obesity, frailty,
and deficiencies in adequate psychosocial support,
grounded in transparent communication of eligibility
criteria to patients and referring clinicians.
• Develop and implement educational interventions that
assist all patients, particularly members of racial and
ethnic minorities, to successfully reach the waitlist
expeditiously.
• Implement scalable and generalizable information tech-
nology solutions to support waitlist access and mainte-
nance of transplant readiness.
Priority 3: Decrease Organ Discard by Expanding
Clinician and Patient Organ Acceptance
Long waiting times for kidney transplantation create a
strong imperative to make the best use of donated organs.
Nearly 10% of individuals with a previously declined
organ offer die on the waitlist without a transplant, and
another 20% are removed from the waitlist without a
transplant. The United States has the highest rate of organ
recovery without transplantation (nonutilization or
“discard”), at nearly 20%.44 The federal government has
focused national attention on increased organ recovery
and reduced organ discard rates as the first objective of
the Advancing American Kidney Health executive order’s
increasing kidney transplant goal.6 There are opportu-
nities to increase the number of deceased donor kidney
transplants by measuring and maximizing the potential
pool of deceased donor kidneys and minimizing the
number of organ nonutilizations.45,46 Expanding the pool
of accepted organs will likely require multifaceted efforts
that address barriers at the levels of patients, transplant
centers, and OPOs.44 Furthermore, researchers and
funding organizations should invest in developing new
technologies to optimize early organ function, assess
transplantability of higher-risk or damaged organs, and
foster the potential to repair injured kidneys prior to
transplant.
There is abundant evidence that many deceased donor
kidneys that could benefit some patients are not utilized
or never recovered. For example, although the number of
patients aged 65 years and older continues to rise (20.5%
of additions to the waiting list in 2020), the average age of
deceased kidney donors has not increased in parallel. A
study comparing deceased donor transplant practices in the
323

Discard Proportion DGF Freedom
100%
88.7% 86.9%
90%
84.0%
89.1%
80%
70%
75.9%
69.9%
60%
50%
40%
30%
20%
19.2%
10%
2.5%
9.5%
0%
Kidney Donor Profile Index
Figure 4. Deceased donor kidneys: use and outcomes. The discard rate rises more rapidly with higher Kidney Donor Profile Index
compared to the graft failure and delayed graft function (DGF) rates. Prepared from Scientific Registry of Transplant Recipients data,
2010-2020.
United States versus France in 2004-2014 found that the
mean donor age of kidneys transplanted in the United
States was substantially lower, 36.2 versus 50.9 years.47
Donor age and mean Kidney Donor Risk Index (KDRI)
steadily rose over time in France, while donor age and
KDRI of kidneys transplanted in the United States showed
little change, suggesting significant untapped donor po-
tential.47 Studies of US registry data demonstrate a strong
relationship between organ quality scores and discard
rates, such that more than 45% of kidneys with Kidney
Donor Profile Index (KPDI) scores >80% are discarded
(Fig 4).45 Despite higher rates of graft failure, high-KDPI
organs can provide survival and quality-of-life benefits
over maintenance dialysis in appropriate patients. A
national registry study found that transplant with high-KDPI
kidneys (defined as KDPI >70) was associated with
increased short-term death risk compared to remaining on
dialysis for 6 additional months. However, these organs
improved long-term survival compared to waiting on dial-
ysis for a higher-quality organ among those who were
older, had diabetes, or were living in areas with prolonged
waiting times.48 The highest-risk organs (KDPI 91-100)
appeared to benefit patients older than age 50 years at
centers with median waiting times longer than 33
months.48
As another example, unilateral discard (in which only 1
of 2 recovered kidneys is transplanted) is a relatively com-
mon occurrence that calls into question the reliability of
organ evaluation. While some discordant discard is expected
324
Lentine et al
Graft Survival (5 yr)
81.1%
76.6%
70.2%
63.5% 67.1%
66.9% 62.4%
53.8%
32.8%
(eg, in the presence of significant nephrolithiasis or surgical
injury), many of these decisions appear to be based on
inaccurate data, including procurement biopsies.49,50 Evi-
dence shows that kidneys are more likely be discarded on
the weekend and that organs that are accepted and suc-
cessfully transplanted on the weekend are declined many
more times before eventually being accepted. Differences in
organ acceptance on a weekend versus a weekday suggests
that factors beyond organ quality and patient issues influ-
ence the willingness of transplant centers to accept an or-
gan.51 Frequently cited reasons for organ offer declines
include the desire to wait for a “better organ offer” for
patients at the top of the waitlist, as well as concerns about
program outcomes.49,51 Taken together, these findings
imply a substantial opportunity to transplant many currently
discarded kidneys, particularly if the offers are targeted to
willing patients and centers.
Many programs report kidney nonutilization due to
concerns for posttransplant outcomes that, if markedly
worse than those at peer centers, may lead to censure by
the Organ Procurement and Transplantation Network/
United Network for Organ Sharing (OPTN/UNOS), loss of
private payer contracts, and decreased transplant volume.52
Additionally, managing delayed graft function (DGF;
typically defined as need for dialysis in the first week after
transplant) creates additional burdens and costs for pro-
grams. These costs pose a significant financial disincentive
for accepting lower-quality kidneys.53 Care of transplant
recipients who need dialysis during weeks 2-12
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Lentine et al
posttransplant requires increased resources and costs.54
Yet, over the life of the organ, there are significant clin-
ical and economic benefits of transplantation with
nonstandard, higher-risk organs.1 Developing alternative
payment methodologies to eliminate financial barriers to
nonstandard organ acceptance is vital to achieve the goal of
increasing organ acceptance.55
Patients and some clinicians may also be dissuaded from
accepting kidneys due to perceived stigma associated with
donors with a history of injection drug use or sex work,
despite the very small probabilistic estimates of viral
transmission to recipients.56 Kidneys from infection risk
donors (IRDs) defined by US Public Health Services (PHS)
criteria continue to be discarded at elevated rates, but
provide significant benefit over dialysis. IRD kidneys are
often high-quality organs from young donors with
excellent long-term survival, which confer minimal
infection transmission risk in the era of universal nucleic
acid testing. In December 2020, the OPTN revised policy
related to IRD organs to align with the 2020 updated US
PHS Guideline, including replacing the requirement to
obtain specific “informed consent” with a requirement
that transplant clinicians inform intended recipients when
the donor has any risk criteria, combined with increased
posttransplant monitoring of all recipients.57 The impact of
this policy change on acceptance of organs from IRD do-
nors by patients and clinicians, and on posttransplant
outcomes, should be closely monitored.
The introduction of direct-acting antiviral (DAA) medi-
cations that achieve sustained viral response (cure) rates
above 95% with few side effects has expanded opportunities
to safely use organs from donors with hepatitis C viremia
(HCV) in uninfected recipients, which, when coupled with
DAA posttransplant therapy, results in excellent outcomes.58
Nonetheless, up to 40% of US transplant programs remain
reluctant to incorporate transplants from donors with HCV
into their practice due to barriers including insurance
coverage concerns, cost, and perceived risk of transmitting
resistant infection.59 The COVID-19 pandemic created an
urgent need to develop tools for rapid and reliable screening
of donors for a new viral infection.60 As the prevalence of
individuals with recovered COVID-19 increases in the
population, determining if and when organs from donors
with recovered COVID-19 can be safely used is a critical
research priority.61,62
Importantly, metrics of transplant success have focused
largely on patient and graft survival. However, for some
patients—especially the elderly—the most important
benefits of transplantation may relate to other domains
such as quality of life or greater social participation.
Freedom from dialysis, even for a shorter period, may be
highly valuable for patients and families.
Recommendations
• Develop and evaluate patient- and clinician-facing educa-
tional materials to foster understanding of the potential
AJKD Vol 78 | Iss 3 | September 2021
benefits of accepting kidneys at risk for discard (KARD),
including organs from donors with older age, lower
quality scores, acute kidney injury, behaviors associated
with viral infections, or certain known viral infections.
• Create and evaluate communication strategies to effec-
tively educate patients and clinicians about organ offers
and promote shared decision-making at listing and
throughout the experience on the waiting list.
• Incorporate additional definitions of success (incremen-
tal survival, quality of life improvement) into models of
transplant acceptance.
Priority 4: Decrease Organ Discard With Use of
Novel Assessment Technologies and Real-Time
Decision Support
Given the growing complexity of organ acceptance to
optimize competing concerns for graft failure versus death
on the waiting list, logistical complexity exacerbated by
geographically broader organ sharing, and clinician con-
cerns for patient and program outcomes, decision support
systems may promote KARD acceptance. Despite wide-
spread use and integration into organ allocation, the KDPI
is a first-generation tool to assess kidney quality that has
modest ability to predict graft survival and carries a sig-
nificant chance of misclassifying risk, which may increase
the likelihood of organ discard.63 Investigators should seek
to develop tools for transplant clinicians to objectively
assess the benefits of specific kidney offers for individual
patients, accounting for logistical realities during time-
sensitive and complex decision-making. These tools
might incorporate machine learning, artificial intelligence
(AI), and other advanced analytics to integrate the complex
clinical information available about donors and candidates
to match organs to appropriate recipients. Efficient in-
terfaces are needed with OPTN/UNOS systems to provide
data in real time without additional data entry. For
example, integrated interpretation of complex serum
creatinine trajectories, renal pathology images, or machine
perfusion parameters such as resistance and flow patterns
could be facilitated by AI or advanced modeling tools.
Clinicians and scientists have proposed multiple expla-
nations for high kidney discard rates in the United States;
however, the primary code used for organ decline is organ
quality, often related to biopsy results.45 Nearly half of
deceased donor kidneys in the United States undergo post-
recovery biopsy to evaluate “quality,”50 despite nearly uni-
form evidence refuting the benefit of these biopsies, which
add to cost and cold ischemia time. A study comparing
allocation in the United States versus France and Bel-
gium—where kidneys are not routinely biopsied during
allocation—reported no predictive value of biopsies over
what is routinely available from donor medical records.64
The reliability of kidney biopsy is further complicated by
the limited availability of trained renal pathologists and the
difficulty of interpreting frozen sections due to artifact.
325

Telepathology allows remote review and image interpreta-
tion, while whole-slide interpretation using AI systems ap-
pears promising to improve reliability of biopsy reports.
Accurate biopsy data utilizing AI solutions could facilitate
more rapid placement of organs, as the community appears
not yet ready to significantly limit biopsies, as some have
proposed.65,66 A pilot trial to assess the feasibility of surgeon
willingness to defer access to biopsy information at the time
of offer acceptance is under way.67
Recommendations
• Identify tissue, urine, or circulating biomarker tools to
better predict kidney graft survival, and inform organ
acceptance decisions.
• Define appropriate use of and approach to procurement
biopsies by:
> Assessing the impact of organ selection without bi-
opsy on patient-centered outcomes (discard, renal
function, graft survival, patient survival).
> Evaluating the accuracy of whole-slide/multilevel bi-
opsy review including AI-supported reading.
• Develop AI systems to integrate complex, multifaceted
information including kidney biopsy data, novel bio-
markers, and other donor risk information to:
> Generate graft survival predictions tailored for patient
clinical profiles.
> Reduce inter-clinician variability in organ acceptance.
Priority 5: Develop and Implement Strategies to
Preserve, Resuscitate, or Evaluate Kidney
Allografts Before Implantation
Technology for preservation of kidney allografts has not
advanced substantially over the past 2 decades. Static cold
storage in electrolyte-rich preservation solutions can allow
successful transplantation of kidneys with prolonged cold
ischemic times (CITs) even exceeding 36 hours. However,
organs preserved with static cold storage alone for
extended periods have high rates of DGF. Hypothermic
pulsatile machine perfusion has been demonstrated to
reduce the incidence of DGF and costs of the transplant
hospitalization. In a randomized trial of 752 paired kid-
neys, machine perfusion resulted in significantly reduced
DGF in transplants with CIT less than 10 hours (6% vs
28%; P < 0.002) but did not significantly decrease DGF in
the context of longer CIT.68 Pulsatile perfusion appears to
have benefits for both standard-criteria and higher-risk
kidneys. A retrospective analysis of US registry data
found reduced DGF rates after pulsatile perfusion of kid-
neys from both standard and higher-risk donors.69
Innovations have extended the benefits of perfusion
technology from preservation alone to organ assessment,
improvement, and resuscitation. While standard hypo-
thermic pulsatile perfusion flow and resistance parameters
have been correlated with graft outcomes, innovations in
perfusion technology promise greater information about
326
Lentine et al
the organ and, potentially, the opportunity to improve its
quality. Normothermic perfusion of kidney allografts can
permit assessment of graft function in an ex vivo setting.
Successful transplant of a kidney with severe acute kidney
injury from rhabdomyolysis following effective warm
perfusion has been reported.70 A prospective trial of
normothermic perfusion is currently under way to assess
impacts on graft utilization and outcome.71
Alternatively, hypothermic oxygenated perfusion can be
performed. A small cohort study comparing extended-
criteria donor kidneys with matched historical controls
(15 perfused kidneys vs 30 controls) failed to demonstrate
significant benefits in rates of DGF or graft failure.
Ongoing trials in Europe are underway to assess the value
of hypothermic oxygenated perfusion in kidney allografts
from extended-criteria donors.72 However, more work is
needed to determine which perfusion techniques lead to
optimal outcomes in different clinical contexts.
Finally, novel methods to improve marginal kidney
function during ex vivo perfusion using pharmacologic,
cellular, and genetic therapies are currently being
explored.73 These therapies are designed to mitigate
ischemic reperfusion injury and diminish alloimmune
activation and organ damage. Ex vivo treatment offers
significant potential advantages. First, the therapy can be
targeted directly to the organ without impacting the po-
tential recipient. Second, the intervention is limited to the
kidney and will not impact other organs recovered from
the same donor. The infusion of mesenchymal stromal
cells has been evaluated as a method to decrease allor-
eactivity and induce tolerance. Mesenchymal stromal cells
can hone in on injured cells and promote recovery through
the release of growth factors and cytokines.74 Preclinical
studies suggest that mesenchymal stromal cell infusion
during normothermic perfusion results in decreased in-
flammatory cytokines and markers of ischemia-reperfusion
injury. Gene therapy, such as methods that have been
widely used in altering T-cell receptor specificity, has been
suggested as a method to promote tolerance, limit the
detrimental effects of ischemic reperfusion, and modify
host–organ interaction in xenotransplantation. The only
clinical trials to date of therapy administration during
kidney perfusion have utilized pharmacologic agents, and
did not yield significant reductions in DGF rates.
Recommendations
• Investigate optimal preservation strategies (including
innovative perfusion technologies) to decrease DGF rates
and improve organ utilization.
• Evaluate novel techniques to monitor transplants during
preservation, improve the accuracy of quality assess-
ments, and optimize utilization.
• Examine ex vivo interventions directed at improving
allograft function, reducing ischemia-reperfusion injury,
and extending the life of donor allografts through im-
mune regulation.
AJKD Vol 78 | Iss 3 | September 2021
Lentine et al
Box 1. Summary of Research Priorities to Advance Kidney Transplant Access and Outcomes
Priority 1: Expand Opportunities for Safe Living Donation and Access to LDKT
Challenges
• Transplant candidates have varying abilities to
share their need and identify potential living
donors
• Lack of information and disincentives may deter
willing, healthy persons from donation:
• Gaps in ensuring donor follow-up and
complete risk assessment
• Economic barriers, including out-of-pocket
expenses and lost wages
Priority 2: Improve Waitlist Access, Management, and Pretransplant Readiness
Challenges
• Racial and ethnic minority populations face dis-
parities in access to transplantation and overall
waitlist mortality
• Weight-loss methods to improve BMI, like
nutritional interventions and bariatric surgery,
are not accessible for many obese patients
• Structured or standardized “prehabilitation” and
physical therapy programs to improve physical
function prior to transplant are not accessible for
many frail patients
• Referral and evaluation are complex, multi-step
processes
Priority 3: Decrease Organ Discard by Expanding Clinician and Patient Organ Acceptance
Challenges
• On average, 20% of kidneys are discarded after
recovery, and this proportion rises sharply for
nonstandard organs
• Patient and clinician perceptions and education
limit acceptance of organs from donors with high
KDPI, increased risk of viral infection, or some
known viral infections
• Metrics of transplant success have focused
largely on patient and graft survival, and not
incorporated QoL
Priority 4: Decrease Organ Discard Through Use of Novel Assessment Technologies and Real-Time Decision
Support
Challenges
• Despite integration into organ allocation, the
KDPI has modest ability to predict graft survival
and may misclassify true organ quality
• Biopsied kidneys are 3-times more likely to be
discarded despite:
> Marked variation in indications for biopsy,
technique, and expertise in interpretation
> Limited reliability of standard frozen section
biopsy and uncertain prognostic value
AJKD Vol 78 | Iss 3 | September 2021
Recommended Research Targets
• Improve education and outreach to kidney patients about
effective strategies for potential donor identification
• Reduce financial disincentives to donation
• Improve the efficiency of donor evaluations and predonation
processes, with particular attention to removing disincentives
and logistical barriers to KPD participation for programs and
patients
• Optimize donor risk assessment and long-term follow-up
• Identify and implement methods to improve risk communica-
tion, transparency, and shared decision-making in the donor
candidate evaluation
Recommended Research Targets
• Optimize strategies to eliminate barriers to waitlist accep-
tance including management of obesity, frailty, and de-
ficiencies in adequate psychosocial support, grounded in
transparent communication of eligibility criteria to patients and
referring clinicians
• Develop and implement educational interventions that assist
all patients, particularly members of racial and ethnic minor-
ities, to successfully reach the waitlist expeditiously
• Implement scalable and generalizable information technology
solutions to support waitlist access and maintenance of
transplant readiness
Recommended Research Targets
• Develop and evaluate patient- and clinician-facing educational
materials to foster understanding of the potential benefits of
accepting a KARD, including organs from donors with older
age, lower quality scores, AKI, behaviors associated with viral
infections, or certain known viral infections
• Create and evaluate communication strategies to effectively
educate patients and clinicians about organ offers and pro-
mote shared decision-making at listing and throughout the
experience onf the waiting list
• Incorporate additional definitions of success (QoL improve-
ment) into models of transplant acceptance
Recommended Research Targets
• Identify tissue, urine, or circulating biomarkers tools to better
predict kidney graft survival and inform organ acceptance
decisions
• Define appropriate use of and approach to procurement bi-
opsies by:
> Assessing the impact of organ selection without biopsy
on patient-centered outcomes (discard, kidney function,
graft survival, patient survival)
> Evaluating the accuracy of whole slide/multilevel review
including AI-supported reading
(Continued)
327
 Lentine et al

(Cont'd).
Priority 5: Develop Strategies to Preserve, Resuscitate, or Evaluate Kidney Allografts Before Implantation
Challenges
• Technology for preservation of kidney allografts
has not advanced substantially over the past 2
decades
• Innovations in organ perfusion, assessment, and
resuscitation are infrequently used
Priority 6: Sustaining One Transplant for Life
Challenges
• Potent IS has substantially reduced acute cellular
and humoral rejection, but long-term graft survival
remains limited
• IS is associated with complications including
infection, malignancy, glucose intolerance,
increased costs of care, and decreased QoL
Priority 7: Optimize Kidney Transplantation for Pediatric Patients
Challenges
• Pediatric kidney failure is associated with multi-
systemic sequelae including impacts on
cognition
• The highest risk period for graft loss among pe-
diatric transplant patients occurs in late teenage/
early adulthood years, prior to complete neuro-
development and concomitant with transition
from pediatric to adult care teams
• Repeat transplantation of children with allograft
failure is complicated by higher rates of
allosensitization
• Children face high risk of viral-driven malignancy
from donor-derived viral infections
Abbreviations: AI, artificial intelligence; AKI, acute kidney injury; BMI, body mass index; GFR, glomerular filtration rate; GWAS, genome-wide association study; KARD,
kidney at risk for discard; KDPI, kidney donor profile index; KPD, kidney paired donation; IRI, ischemic reperfusion injury; IS, immunosuppression; LDKT, living-donor
kidney transplantation; QoL, quality of life.
• Develop AI systems to integrate complex, multifaceted infor-
mation including kidney biopsy data, novel biomarkers and
other donor risk information to:
> Generate graft survival predictions tailored for patient
clinical profiles
> Reduce inter-clinician variability in organ acceptance
Recommended Research Targets
• Investigate optimal preservation strategies (including innova-
tive perfusion technologies) to decrease DGF rates and
improve organ utilization
• Evaluate novel techniques to monitor transplants during
preservation, improve the accuracy of quality assessments,
and optimize utilization
• Examine ex vivo interventions directed at improving allograft
function, reducing IRI, and extending the life of donor allo-
grafts through immune regulation
Recommended Research Targets
• Develop personalized strategies for posttransplant IS man-
agement incorporating novel assessment tools such as
GWAS data for donors and recipients and novel posttrans-
plant monitoring tools
• Assess the impact of tolerance induction strategies on patient
and graft survival, QoL, and development of IS complications
Recommended Research Targets
• Evaluate strategies to improve coordination of care transitions
between pediatric and adult transplant clinicians
• Identify approaches to improve medication adherence and
reduce early graft loss while protecting the neurocognitive
development of children and adolescents
• Optimize organ allocation and IS management to reduce the
incidence and complications of viral diseases in pediatric
recipients

Priority 6: Sustain One Transplant for Life
Although contemporary tissue-typing techniques have
essentially eliminated hyperacute rejection, and potent
immunosuppression has substantially reduced acute cellular
and humoral rejection, long-term graft survival remains
limited. Furthermore, immunosuppression is associated with
complications including infection, malignancy, glucose
intolerance, and decreased quality of life.75 Personalization of
maintenance immunosuppression with appropriate applica-
tions of steroid-sparing regimens, alternative pharmacologic
agents (eg, extended-release tacrolimus), and judicious use of
mammalian target of rapamycin inhibitors (mTORis) may
limit immunosuppression-associated toxicities.76,77 Howev-
er, novel strategies are needed to achieve the goal of one
transplant for life.
The development of personalized and effective immu-
nosuppression strategies requires a shift from phenotypic
(eg, demographics-based) assessments to genotypic
assessment of patient characteristics.23 Accurate models
require the collection and analysis of biobanks from large
and diverse patient populations. In the DeKAF and GEN03
cohort studies, investigators utilized genome-wide

328 AJKD Vol 78 | Iss 3 | September 2021

Lentine et al
association studies (GWAS) to detect clinically significant
differences in calcineurin inhibitor metabolism on the basis of
a complex interaction of multiple genetic polymorphisms.78
These data demonstrate that the impact of recipient genetic
variation is complex, differs by patient characteristics, and
extends beyond well-characterized genomic variation (eg,
CYP34). Developing clinical application of genotypic data
will benefit from systematic collection and analysis of donor
and recipient genetic variations through GWAS, linked
directly with baseline clinical and outcomes information.
Belatacept, a soluble fusion protein comprising the
modified extracellular domain of CTLA-4 fused to a portion
(hinge-CH2-CH3 domains) of the Fc domain of a human
immunoglobulin G1 antibody, has been evaluated in 2
prospective clinical trials as a novel alternative to oral
immunosuppression.79 While initial studies suggested high
rates of rejection, pilot studies combining belatacept,
alemtuzumab induction, and slow tapering of calcineurin
inhibitors have facilitated successful belatacept mono-
therapy in some patients. Alternative strategies under
investigation include use of combined cellular and kidney
transplantation to induce a state of “tolerance” through
chimerism, allowing tapering and elimination of mainte-
nance immunosuppression.80,81 Incorporation of novel
biomarkers into posttransplant surveillance may help
identify which patients have lower immunologic risk and
could benefit from immunosuppression minimization to
reduce complications without increasing risk of rejection.82
Recommendations
• Develop personalized strategies for posttransplant
immunosuppression management, incorporating novel
assessment tools such as GWAS data for donors and re-
cipients and novel posttransplant monitoring tools.
• Assess the impact of tolerance induction strategies on
patient and graft survival, quality of life, and develop-
ment of immunosuppression complications.
Priority 7: Optimize Kidney Transplantation for
Pediatric Patients
Although patients younger than 20 years of age account
for less than 2% of the total North American patient
population treated by kidney replacement therapy, the
prevalence of pediatric kidney failure has increased by 32%
since 1990.83,84 Approximately 50% of all pediatric kidney
failure diagnoses are due to congenital, nonglomerular
anomalies,85 and half of all pediatric patients with
congenital kidney disease will progress to a need for
transplantation during their lifetime.84 Pediatric kidney
failure is associated with an array of multisystemic
sequelae, and the impact of kidney failure on cognition has
important implications for optimizing outcomes of trans-
plantation in the pediatric population.86 Pediatric kidney
failure is associated with risk for academic underachieve-
ment87 and executive function deficits.88 Furthermore,
both the duration and severity of kidney disease in pediatric
AJKD Vol 78 | Iss 3 | September 2021
patients may lead to structural brain abnormalities.89 While
significant cognitive impairment may not be present in most
children with chronic kidney disease, even subtle cognitive
impairments can pose barriers to understanding of and
adherence to complex medication regimens required as part
of caring for a transplant. The impact of these subtle
cognitive deficits cannot be overemphasized given that the
highest-risk period for graft loss among pediatric transplant
patients occurs in late teenage/early adulthood years when
critical periods of neurodevelopment are not yet complete,
in parallel with periods of transition from pediatric to adult
care teams.90 Children also face high risk of viral-driven
malignancy from donor-derived viral infections.
Recommendations
• Evaluate strategies to improve coordination of care transi-
tions between pediatric and adult transplant clinicians.
• Identify approaches to improve medication adherence
and reduce early graft loss while protecting the neuro-
cognitive development of children and adolescents.
• Optimize organ allocation and immunosuppresion
management to reduce the incidence and complciations
of viral diseases in pediatric recipients.
Conclusions
Kidney transplantation offers hope to thousands of patients
each year, but the goal of universal access to this treatment
remains elusive. Addressing the priorities outlined in this
research agenda has the potential to transform kidney pa-
tient care by expanding opportunities for safe living
donation, improving waitlist access and transplant readi-
ness, maximizing use of available deceased donor organs,
and extending graft longevity. These priorities will frame
research and funding initiatives for the NKF and assist
patients with chronic kidney disease in receiving and
nurturing the gift of transplant (Box 1).
Article Information
Authors’ Full Names and Academic Degrees: Krista L. Lentine,
MD, PhD, Stephen Pastan, MD, Sumit Mohan, MD, MPH, Peter P.
Reese, MD, MSCE, Alan Leichtman, MD, Francis L. Delmonico,
MD, Gabriel M. Danovitch, MD, Christian P. Larsen, MD, PhD,
Lyndsay Harshman, MD, MS, Alexander Wiseman, MD, Holly J.
Kramer, MD, MPH, Joseph Vassalotti, MD, Jessica Joseph, MBA,
Kevin Longino, MBA, Matthew Cooper, MD, and David A. Axelrod,
MD, MBA.
Authors’ Affiliations: Saint Louis University Center for Abdominal
Transplantation, St Louis, MO (KLL); Department of Medicine,
Emory Transplant Center, Atlanta, GA (SP); Department of
Medicine, Columbia University Medical Center (SM); National
Kidney Foundation (JV, JJ, KL); Department of Medicine, Icahn
School of Medicine at Mount Sinai (JV), New York, NY; Renal-
Electrolyte and Hypertension Division, University of Pennsylvania,
Philadelphia, PA (PPR); Department of Medicine, Icahn School of
Medicine at Mount Sinai, New York, NY (AL); New England Organ
Bank, Wellesley Hills, MA (FLD); University of California, Los
Angeles, Los Angeles, CA (GMD); Department of Pediatrics (LH),
Department of Surgery (DAA), University of Iowa Transplant
329

Institute, Iowa City, IA (LH); Department of Medicine, Centura
Health-Porter Adventist Hospital, Aurora, CO (AW); Department of
Medicine, Loyola University, Chicago, IL (HJK); Department of
Surgery, Medstar Georgetown Transplant Institute, Washington,
DC (MC) and Department of Surgery, Emory Transplant Center,
Atlanta, GA (CPL).
Address for Correspondence: Krista L. Lentine, MD, PhD, Saint
Louis University Center for Abdominal Transplantation, 1201 S
Grand Blvd, St Louis, MO, 63104. Email: krista.lentine@health.slu.
edu
Support: The Transplant Research Roundtable was supported by
the National Kidney Foundation. No additional support was obtained.
Financial Disclosure: Dr Lentine reports receiving consulting fees
from CareDx, speaker honoraria from Sanofi, and research support
from the National Institutes of Health (NIH; U01DK116042,
R01DK120551, and R01DK125018) and the Mid-America
Transplant Foundation; she is a senior scientist of the Scientific
Registry of Transplant Recipients. Dr Pastan reports membership
on the Board of Directors for the NKF and the Forum of End-Stage
Renal Disease (ESRD) Networks, and is a Chairman of the local
Board of IPRO/ESRD Network 6. Dr Mohan reports grant support
from NIH (R01DK126739, U01DK114893, and R01MD014161)
and Angion Biomedica and personal fees from Kidney International
Reports and Angio Biomedica. Dr Reese reports having received
research support to the University of Pennsylvania from Merck,
AbbVie, and Gilead to investigate transplantation of hepatitis C
virus–infected organs into uninfected recipients followed by antiviral
treatment; serves as AJKD Associate Editor; and is an unpaid
consultant to eGenesis, a company developing xenotransplantation
technology. Dr Leichtman is a consultant to Arbor Research
Collaborative for Health, a member of the governing board of Gift of
Life Michigan, and a partner in Compass Integrated Care. Dr
Delmonico reports receiving salary from the New England Donor
Services in Massachusetts General Hospital. Dr Wiseman reports
receiving consultant fees for Veloxis, CareDx, and Natera, and has
received speaking fees for Veloxis. Dr Kramer reports membership
on the NKF Board of Directors, serves as a consultant for Bayer
Pharmaceuticals, and serves as AJKD Engagement Editor. Dr
Vassalotti reports having served on a CKD advisory board for
Renalytix AI, PLC. Ms Joseph and Mr Longino are employed by the
NKF. Dr Cooper reports membership on the NKF Board of
Directors. Dr Axelrod reports receiving consultation fees from
CareDx and Talaris and serves on the advisory board for Veloxis.
The remaining authors declare that they have no relevant financial
interests.
Acknowledgements: The authors thank Debra Taylor, MPH, for
assistance with manuscript preparation. The authors also thank
Saint Louis University biostatisticians Huiling Xiao, MS, and Ruixin
Li, MS, for assistance with SRTR data analysis and figure
preparation. Data reported here have been supplied by the
Hennepin Healthcare Research Institute (HHRI) as the contractor
for the Scientific Registry of Transplant Recipients (SRTR). The
interpretation and reporting of these data are the responsibility of
the authors and in no way should be seen as an official policy of
or interpretation by the SRTR or the US Government.
Peer Review: Received April 17, 2021, following review and
approval by the NKF Scientific Advisory Board (membership listed
at https://www.kidney.org/about/sab) and the NKF Executive
Committee (listed at https://www.kidney.org/about/board).
Accepted May 1, 2021, after editorial review by a Deputy Editor.
References
1. Axelrod DA, Schnitzler MA, Xiao H, et al. An economic
assessment of contemporary kidney transplant practice. Am J
Transplant. 2018;18(5):1168-1176.
330
Lentine et al
2. Alhamad T, Axelrod D, Lentine KL. The epidemiology, out-
comes, and costs of contemporary kidney transplantation.
In: Himmelfarb J, Ikizler TA, eds. Chronic Kidney Disease,
Dialysis, and Transplantation: A Companion to Brenner
and Rector’s the Kidney. 4th ed. Elsevier; 2019:chapter
34.
3. Hart A, Lentine KL, Smith JM, et al. OPTN/SRTR 2019 Annual
Data Report: kidney. Am J Transplant. 2021;21(suppl 2):21-
137.
4. Alhamad T, Lubetzky M, Lentine KL, et al. Kidney recipients with
allograft failure, transition of kidney care (KRAFT): a survey of
contemporary practices of transplant providers. Am J Trans-
plant. 2021. Published online February 8, 2021. doi:10.1111/
ajt.16523.
5. Purnell TS, Luo X, Cooper LA, et al. Association of race and
ethnicity with live donor kidney transplantation in the United
States from 1995 to 2014. JAMA. 2018;319(1):49-61.
6. Lentine KL, Mannon RB. The Advancing American Kidney
Health (AAKH) Executive Order: promise and caveats for
expanding access to kidney transplantation. Kidney360.
2020;1(6):557-560.
7. Pereira MR, Mohan S, Cohen DJ, et al. COVID-19 in
solid organ transplant recipients: Initial report from the
US epicenter. Am J Transplant. 2020;20(7):1800-1808.
8. Lentine KL, Vest LS, Schnitzler MA, et al. Survey of US
living kidney donation and transplantation practices in the
COVID-19 era. Kidney Int Rep. 2020;5(11):1894-1905.
9. Lentine KL, Mannon RB, Josephson MA. Practicing with
uncertainty: kidney transplantation during the COVID-19
pandemic. Am J Kidney Dis. 2021;77(5):777-785.
10. Lentine KL, Mandelbrot D. Moving from intuition to data:
building the evidence to support and increase living donor
kidney transplantation. Clin J Am Soc Nephrol. 2017;12(9):
1383-1385.
11. Garg N, Gill J, Mandelbrot DA. Compatibility, kidney paired
donation, and incompatible living donor transplants. In:
Lentine KL, Concepcion BP, Lerma EV, eds. Living Kidney
Donation: Best Practices in Evaluation, Care and Follow-up.
Springer International; 2021:233-251.
12. Melcher ML, Leeser DB, Gritsch HA, et al. Chain trans-
plantation: initial experience of a large multicenter program. Am
J Transplant. 2012;12(9):2429-2436.
13. Massie AB, Gentry SE, Montgomery RA, Bingaman AA,
Segev DL. Center-level utilization of kidney paired donation. Am
J Transplant. 2013;13(5):1317-1322.
14. Gentry SE, Segev DL, Simmerling M, Montgomery RA.
Expanding kidney paired donation through participation by
compatible pairs. Am J Transplant. 2007;7(10):2361-2370.
15. Veale JL, Capron AM, Nassiri N, et al. Vouchers for future
kidney transplants to overcome “chronological incompatibility”
between living donors and recipients. Transplantation.
2017;101(9):2115-2119.
16. Hunt HF, Rodrigue JR, Dew MA, et al. Strategies for
increasing knowledge, communication, and access to living
donor transplantation: an evidence review to inform patient
education. Curr Transplant Rep. 2018;5(1):27-44.
17. Barnieh L, Collister D, Manns B, et al. A scoping review for
strategies to increase living kidney donation. Clin J Am Soc
Nephrol. 2017;12(9):1518-1527.
18. Rodrigue JR, Cornell DL, Kaplan B, Howard RJ. A randomized
trial of a home-based educational approach to increase live
donor kidney transplantation: effects in blacks and whites. Am J
Kidney Dis. 2008;51(4):663-670.
19. Ismail SY, Luchtenburg AE, Timman R, et al. Home-based family
intervention increases knowledge, communication and living
AJKD Vol 78 | Iss 3 | September 2021
Lentine et al
donation rates: a randomized controlled trial. Am J Transplant.
2014;14(8):1862-1869.
20. Schweitzer EJ, Yoon S, Hart J, et al. Increased living donor
volunteer rates with a formal recipient family education pro-
gram. Am J Kidney Dis. 1997;29(5):739-745.
21. Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk pro-
jection for the living kidney-donor candidate. N Engl J Med.
2016;374(5):411-421.
22. Grams ME, Garg AX, Lentine KL. Kidney-failure risk projection
for the living kidney-donor candidate. N Engl J Med.
2016;374(21):2094-2095.
23. Lentine KL, Mannon RB. Apolipoprotein L1: role in the evalu-
ation of kidney transplant donors. Curr Opin Nephrol Hyper-
tens. 2020;29(6):645-655.
24. Lentine KL, Kasiske BL, Levey AS, et al. KDIGO Clinical
Practice Guideline on the evaluation and care of living kidney
donors. Transplantation. 2017;101(8S)(suppl 1):S1-S109.
25. Kasiske BL, Asrani SK, Dew MA, et al. The Living Donor Col-
lective: a scientific registry for living donors. Am J Transplant.
2017;17(12):3040-3048.
26. Kasiske BL, Ahn YS, Conboy M, et al. Outcomes of
living kidney donor candidate evaluations in the Living
Donor Collective pilot registry. Transplant Direct.
2021;7(5):e689.
27. Lentine KL, Mandelbrot D. Addressing disparities in living donor
kidney transplantation: a call to action. Clin J Am Soc Nephrol.
2018;13(12):1909-1911.
28. Tushla L, Rudow DL, Milton J, et al. Living-donor
kidney transplantation: reducing financial barriers to
live kidney donation–recommendations from a consensus
conference. Clin J Am Soc Nephrol. 2015;10(9):
1696-1702.
29. Habbous S, Woo J, Lam NN, et al. The efficiency of evaluating
candidates for living kidney donation: a scoping review.
Transplant Direct. 2018;4(10):e394.
30. Habbous S, Barnieh L, Klarenbach S, et al. Evaluating
multiple living kidney donor candidates simultaneously is more
cost-effective than sequentially. Kidney Int. 2020;98(6):1578-
1588.
31. Organ Procurement and Transplantation Network (OPTN).
Current U.S. waiting list. Accessed March 10, 2021. https://
optn.transplant.hrsa.gov/data/view-data-reports/national-data/#
32. Grams ME, Massie AB, Schold JD, Chen BP, Segev DL.
Trends in the inactive kidney transplant waitlist and implications
for candidate survival. Am J Transplant. 2013;13(4):1012-
1018.
33. Huang E, Shye M, Elashoff D, Mehrnia A, Bunnapradist S.
Incidence of conversion to active waitlist status among
temporarily inactive obese renal transplant candidates. Trans-
plantation. 2014;98(2):177-186.
34. Ng YH, Pankratz VS, Leyva Y, et al. Does racial disparity in
kidney transplant waitlisting persist after accounting for social
determinants of health? Transplantation. 2020;104(7):1445-
1455.
35. Nishio-Lucar AG, Locke J, Kumar V. Use of patient navigators to
reduce barriers in living donation and living donor trans-
plantation. Curr Transpl Rep. 2020;7(2):72-80.
36. Kataria A, Gowda M, Lamphron BP, Jalal K, Venuto RC,
Gundroo AA. The impact of systematic review of status 7 pa-
tients on the kidney transplant waitlist. BMC Nephrol.
2019;20(1):174.
37. Lentine KL, Delos Santos R, Axelrod D, Schnitzler MA,
Brennan DC, Tuttle-Newhall JE. Obesity and kidney transplant
candidates: how big is too big for transplantation? Am J
Nephrol. 2012;36(6):575-586.
AJKD Vol 78 | Iss 3 | September 2021
38. Lentine KL. Pro: Pretransplant weight loss: yes. Nephrol Dial
Transplant. 2015;30(11):1798-1803.
39. Modanlou KA, Muthyala U, Xiao H, et al. Bariatric surgery
among kidney transplant candidates and recipients: analysis of
the United States renal data system and literature review.
Transplantation. 2009;87(8):1167-1173.
40. Orandi BJ, Purvis JW, Cannon RM, et al. Bariatric surgery to
achieve transplant in end-stage organ disease patients: a sys-
tematic review and meta-analysis. Am J Surg. 2020;220(3):
566-579.
41. Kobashigawa J, Dadhania D, Bhorade S, et al. Report from the
American Society of Transplantation on frailty in solid organ
transplantation. Am J Transplant. 2019;19(4):984-994.
42. Cheng XS, Lentine KL, Koraishy FM, Myers J, Tan JC. Impli-
cations of frailty for peritransplant outcomes in kidney trans-
plant recipients. Curr Transplant Rep. 2019;6(1):16-25.
43. Harhay MN, Rao MK, Woodside KJ, et al. An overview of frailty
in kidney transplantation: measurement, management and
future considerations. Nephrol Dial Transplant. 2020;35(7):
1099-1112.
44. Cooper M, Formica R, Friedewald J, et al. Report of
National Kidney Foundation consensus conference to
decrease kidney discards. Clin Transplant. 2019;33(1):
e13419.
45. Reese PP, Harhay MN, Abt PL, Levine MH, Halpern SD. New
solutions to reduce discard of kidneys donated for trans-
plantation. J Am Soc Nephrol. 2016;27(4):973-980.
46. Schold JD, Meier-Kriesche HU. Which renal transplant candi-
dates should accept marginal kidneys in exchange for a shorter
waiting time on dialysis? Clin J Am Soc Nephrol. 2006;1(3):
532-538.
47. Aubert O, Reese PP, Audry B, et al. Disparities in
acceptance of deceased donor kidneys between the
United States and France and estimated effects of increased
US acceptance. JAMA Intern Med. 2019;179(10):1365-1374.
48. Massie AB, Luo X, Chow EK, Alejo JL, Desai NM, Segev DL.
Survival benefit of primary deceased donor transplantation with
high-KDPI kidneys. Am J Transplant. 2014;14(10):2310-2316.
49. Husain SA, Chiles MC, Lee S, et al. Characteristics and per-
formance of unilateral kidney transplants from deceased do-
nors. Clin J Am Soc Nephrol. 2018;13(1):118-127.
50. Lentine KL, Naik AS, Schnitzler MA, et al. Variation in use of
procurement biopsies and its implications for discard of
deceased donor kidneys recovered for transplantation. Am J
Transplant. 2019;19(8):2241-2251.
51. Mohan S, Foley K, Chiles MC, et al. The weekend effect alters
the procurement and discard rates of deceased donor kidneys
in the United States. Kidney Int. 2016;90(1):157-163.
52. Schold JD, Buccini LD, Srinivas TR, et al. The association of
center performance evaluations and kidney transplant volume
in the United States. Am J Transplant. 2013;13(1):67-75.
53. Axelrod DA, Malinoski D, Patel MS, et al. Modeling the eco-
nomic benefit of targeted mild hypothermia in deceased donor
kidney transplantation. Clin Transplant. 2019;33(7):e13626.
54. Buchanan PM, Schnitzler MA, Axelrod D, Salvalaggio PR,
Lentine KL. The clinical and financial burden of early dialysis
after deceased donor kidney transplantation. J Nephrol Ther.
2012;2012(suppl 4).
55. Schwantes IR, Schnitzler MA, Lentine KL, Balakrishnan R, Reed AI,
Axelrod DA. A simple risk-based reimbursement system for kidney
transplant. Clin Transplant. 2021;35(1):e14068.
56. Ros RL, Kucirka LM, Govindan P, Sarathy H, Montgomery RA,
Segev DL. Patient attitudes toward CDC high infectious risk
donor kidney transplantation: inferences from focus groups.
Clin Transplant. 2012;26(2):247-253.
331

57. Organ Procurement and Transplantation Network (OPTN). Align
OPTN Policy with US PHS Guideline 2020. Board Action:
December 2020. Accessed April 17, 2021. https://optn.
transplant.hrsa.gov/governance/policy-notices/
58. Goldberg DS, Abt PL, Blumberg EA, et al. Trial of trans-
plantation of HCV-infected kidneys into uninfected recipients.
N Engl J Med. 2017;376(24):2394-2395.
59. Lentine KL, Peipert JD, Alhamad T, et al. Survey of clinician
opinions on kidney transplantation from hepatitis C virus posi-
tive donors: identifying and overcoming barriers. Kidney360.
2020;1(11):1291-1299.
60. Lentine KL, Singh N, Woodside KJ, et al. COVID-19 test
reporting for deceased donors: emergent policies, logistical
challenges and future directions. Clin Transplant. 2021;35(5):
e14280.
61. Neidlinger NA, Smith JA, D’Alessandro AM, et al. Organ re-
covery from deceased donors with prior COVID-19: a case
series. Transpl Infect Dis. 2020;23(2):e13503.
62. Jan MY, Jawed AT, Barros N, et al. A national survey of practice
patterns for accepting living kidney donors with prior covid-19.
Kidney Int Reports. Published online May 15, 2021;doi:10.
1016/j.ekir.2021.05.003.
63. Bae S, Massie AB, Luo X, Anjum S, Desai NM, Segev DL.
Changes in discard rate after the introduction of the Kidney
Donor Profile Index (KDPI). Am J Transplant. 2016;16(7):2202-
2207.
64. Reese PP, Aubert O, Naesens M, et al. Assessment of the utility
of kidney histology as a basis for discarding organs in the
United States: a comparison of international transplant prac-
tices and outcomes. J Am Soc Nephrol. 2021;32(2):397-409.
65. Stewart ZA, Shah SA, Formica RN, et al. A call to action:
feasible strategies to reduce the discard of transplantable kid-
neys in the United States. Clin Transplant. 2020;34(9):e13990.
66. Lentine KL, Kasiske BL, Axelrod D. Procurement biopsies
in kidney transplantation: More information may not lead to
better decisions. J Am Soc Nephrol. 2021;32(7):ASN.20210
30403.
67. Trial to define the benefits and harms of deceased donor kidney
procurement biopsies. ClinicalTrials.gov identifier:
NCT03837522. Accessed April 17, 2021. https://clinicaltrials.
gov/ct2/show/NCT03837522
68. Kox J, Moers C, Monbaliu D, et al. The benefits of hypothermic
machine preservation and short cold ischemia times in
deceased donor kidneys. Transplantation. 2018;102(8):1344-
1350.
69. Gill J, Dong J, Eng M, Landsberg D, Gill JS. Pulsatile perfusion
reduces the risk of delayed graft function in deceased donor
kidney transplants, irrespective of donor type and cold ischemic
time. Transplantation. 2014;97(6):668-674.
70. Pearson R, Asher J, Jackson A, Mark PB, Shumeyko V,
Clancy MJ. Viability assessment and utilization of declined
donor kidneys with rhabdomyolysis using ex vivo normothermic
perfusion without preimplantation biopsy. Am J Transplant.
2021;21(3):1317-1321.
71. Hosgood SA, Saeb-Parsy K, Wilson C, Callaghan C, Collett D,
Nicholson ML. Protocol of a randomised controlled, open-label
trial of ex vivo normothermic perfusion versus static cold stor-
age in donation after circulatory death renal transplantation.
BMJ Open. 2017;7(1):e012237.
72. Meister FA, Czigany Z, Bednarsch J, et al. Hypothermic
oxygenated machine perfusion of extended criteria kidney
allografts from brain dead donors: protocol for a prospec-
tive pilot study. JMIR Res Protoc. 2019;8(10):e14622.
332
Lentine et al
73. DiRito JR, Hosgood SA, Tietjen GT, Nicholson ML. The future
of marginal kidney repair in the context of normothermic
machine perfusion. Am J Transplant. 2018;18(10):
2400-2408.
74. Fiori S, Remuzzi G, Casiraghi F. Update on mesenchymal
stromal cell studies in organ transplant recipients. Curr Opin
Organ Transplant. 2020;25(1):27-34.
75. Dharnidharka VR, Schnitzler MA, Chen J, et al. Differential risks
for adverse outcomes 3 years after kidney transplantation
based on initial immunosuppression regimen: a national study.
Transpl Int. 2016;29(11):1226-1236.
76. Cheungpasitporn W, Lentine KL, Tan JC, et al. Immunosup-
pression considerations for older kidney transplant recipients.
Curr Transpl Rep. 2021;8:100-110.
77. Lentine KL, Cheungpasitporn W, Xiao H, et al. Immunosuppres-
sion regimen use and outcomes in older and younger adult kidney
transplant recipients: a national registry analysis. Transplantation.
2021;105(8):1840-1849.
78. Oetting WS, Wu B, Schladt DP, et al. Genetic variants asso-
ciated with immunosuppressant pharmacokinetics and adverse
effects in the DeKAF Genomics Genome-wide Association
Studies. Transplantation. 2019;103(6):1131-1139.
79. Vincenti F, Charpentier B, Vanrenterghem Y, et al. A phase III
study of belatacept-based immunosuppression regimens
versus cyclosporine in renal transplant recipients (BENEFIT
study). Am J Transplant. 2010;10(3):535-546.
80. Busque S, Scandling JD, Lowsky R, et al. Mixed chimerism and
acceptance of kidney transplants after immunosuppressive
drug withdrawal. Sci Transl Med. 2020;12(528).
81. Tantisattamo E, Leventhal JR, Mathew JM, Gallon L. Chimerism
and tolerance: past, present and future strategies to prolong
renal allograft survival. Curr Opin Nephrol Hypertens.
2021;30(1):63-74.
82. Mannon RB, Morris RE, Abecassis M, et al. Use of biomarkers
to improve immunosuppressive drug development and out-
comes in renal organ transplantation: A meeting report. Am J
Transplant. 2020;20(6):1495-1502.
83. Warady BA, Chadha V. Chronic kidney disease in children:
the global perspective. Pediatr Nephrol. 2007;22(12):1999-
2009.
84. Seikaly MG, Ho PL, Emmett L, Fine RN, Tejani A. Chronic renal
insufficiency in children: the 2001 Annual Report of the
NAPRTCS. Pediatr Nephrol. 2003;18(8):796-804.
85. North American Pediatric Renal Trials and Collaborative Studies.
NAPRTCS 2014 Annual Transplant Report. North American
Pediatric Renal Trials and Collaborative Studies; 2014.
86. Dharnidharka VR, Fiorina P, Harmon WE. Kidney transplantation
in children. N Engl J Med. 2014;371(6):549-558.
87. Harshman LA, Johnson RJ, Matheson MB, et al. Academic
achievement in children with chronic kidney disease: a report
from the CKiD cohort. Pediatr Nephrol. 2019;34(4):689-
696.
88. Lande MB, Mendley SR, Matheson MB, et al. Association of
blood pressure variability and neurocognition in children with
chronic kidney disease. Pediatr Nephrol. 2016;31(11):2137-
2144.
89. Solomon MA, van der Plas E, Langbehn KE, et al. Early pedi-
atric chronic kidney disease is associated with brain volumetric
gray matter abnormalities. Pediatr Res. 2021;89(3):526-532.
90. Foster BJ, Dahhou M, Zhang X, Platt RW, Samuel SM,
Hanley JA. Association between age and graft failure rates in
young kidney transplant recipients. Transplantation.
2011;92(11):1237-1243.
AJKD Vol 78 | Iss 3 | September 2021