Generating strategies for a national comeback in pancreas transplantation: A Delphi survey and US conference report.

In the United States, potential transplant candidates with insulin-dependent diabetes mellitus are inconsistently offered pancreas transplantation (PTx), contributing to a dramatic decline in pancreas allograft utilization over the past 2 decades. The American Society of Transplantation organized a workshop to identify barriers inhibiting PTx and to develop strategies for a national comeback. The 2-day workshop focused on 4 main topics: (1) referral/candidate selection, (2) organ recovery/utilization, (3) program performance/patient outcomes, and (4) enhanced education/research. Topics were explored through expert presentations, patient testimonials, breakout sessions, and strategic planning, including the identification of tasks for immediate focus. Additionally, a modified-Delphi survey was conducted among workshop members to develop and rate the importance of barriers, and the impact and feasibility of workgroup-identified improvement strategies. The panelists identified 16 barriers to progress and 44 strategies for consideration. The steps for a national comeback in PTx involve greater emphasis on efficient referral and candidate selection, better donor pancreas utilization practices, eliminating financial barriers to procurement and transplant, improving collaboration between transplant and diabetes societies and professionals, and increasing focus on PTx training, education, and research. Partnership between national societies, patient advocacy groups, and professionals will be essential to realizing this critical agenda.

A Microsimulation Study of the Cost-Effectiveness of Hepatitis C Virus Screening Frequencies in Hemodialysis Centers.

BACKGROUND: National guidelines recommend twice-yearly hepatitis C virus (HCV) screening for patients receiving in-center hemodialysis. However, studies examining the cost-effectiveness of HCV screening methods or frequencies are lacking. METHODS: We populated an HCV screening, treatment, and disease microsimulation model with a cohort representative of the US in-center hemodialysis population. Clinical outcomes, costs, and cost-effectiveness of the Kidney Disease Improving Global Outcomes (KDIGO) 2018 guidelines-endorsed HCV screening frequency (every 6 months) were compared with less frequent periodic screening (yearly, every 2 years), screening only at hemodialysis initiation, and no screening. We estimated expected quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) between each screening strategy and the next less expensive alternative strategy, from a health care sector perspective, in 2019 US dollars. For each strategy, we modeled an HCV outbreak occurring in 1% of centers. In sensitivity analyses, we varied mortality, linkage to HCV cure, screening method (ribonucleic acid versus antibody testing), test sensitivity, HCV infection rates, and outbreak frequencies. RESULTS: Screening only at hemodialysis initiation yielded HCV cure rates of 79%, with an ICER of $82,739 per QALY saved compared with no testing. Compared with screening at hemodialysis entry only, screening every 2 years increased cure rates to 88% and decreased liver-related deaths by 52%, with an ICER of $140,193. Screening every 6 months had an ICER of $934,757; in sensitivity analyses using a willingness-to-pay threshold of $150,000 per QALY gained, screening every 6 months was never cost-effective. CONCLUSIONS: The KDIGO-recommended HCV screening interval (every 6 months) does not seem to be a cost-effective use of health care resources, suggesting that re-evaluation of less-frequent screening strategies should be considered.

Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

A survey of solid organ transplant recipient attitudes and concerns regarding contraception and pregnancy.

INTRODUCTION: Many women who are solid organ transplant (SOT) recipients wish to have children after transplantation. Contraception is an important component of post-transplant planning and care, given the increased risk associated with post-transplant pregnancies. We sought to understand patient attitudes and concerns about post-transplant contraception and pregnancy. METHODS: Following a comprehensive literature review, our team developed a survey that was administered to female SOT recipients of childbearing age. We used descriptive and inferential statistics to characterize participant views RESULTS: A total of 243 transplant recipients completed the survey (80.7% response rate). The mean age of respondents was 37.5 years (±8.1 years), 66.7% were kidney recipients, and 40.7% were within the first year after transplant. The most common concerns among respondents included fetal and maternal health complications. Participants generally did not agree that transplant recipients should be advised to avoid pregnancy. There was strong support for shared decision-making about pregnancy after transplantation CONCLUSION: Understanding patient perspectives can help transplant providers make better care recommendations and support patient autonomy in reproductive decisions post-transplant. Given that there are some differences in views by transplant type, individualized conversations between patients and providers are needed.

Social network interventions to reduce race disparities in living kidney donation: Design and rationale of the friends and family of kidney transplant patients study (FFKTPS).

INTRODUCTION: Racial/ethnic disparities in living donor kidney transplantation (LDKT) are a persistent challenge. Although nearly all directed donations are from members of patients' social networks, little is known about which social network members take steps toward living kidney donation, which do not, and what mechanisms contribute to racial/ethnic LDKT disparities. METHODS: We describe the design and rationale of the Friends and Family of Kidney Transplant Patients Study, a factorial experimental fielding two interventions designed to promote LKD discussions. Participants are kidney transplant candidates at two centers who are interviewed and delivered an intervention by trained center research coordinators. The search intervention advises patients on which social network members are most likely to be LKD contraindication-free; the script intervention advises patients on how to initiate effective LKD discussions. Participants are randomized into four conditions: no intervention, search only, script only, or both search and script. Patients also complete a survey and optionally provide social network member contact information so they can be surveyed directly. This study will seek to enroll 200 transplant candidates. The primary outcome is LDKT receipt. Secondary outcomes include live donor screening and medical evaluations and outcomes. Tertiary outcomes include LDKT self-efficacy, concerns, knowledge, and willingness, measured before and after the interventions. CONCLUSION: This study will assess the effectiveness of two interventions to promote LKD and ameliorate Black-White disparities. It will also collect unprecedented information on transplant candidates' social network members, enabling future work to address network member structural barriers to LKD.

Ignorance is Not Bliss: The Case for Comprehensive Reproductive Counseling for Women with Chronic Kidney Disease.

The bioethics literature has paid little attention to matters of informed reproductive decision-making among women of childbearing age who have chronic kidney disease (CKD), including women who are on dialysis or women who have had a kidney transplant. Women with CKD receive inconsistent and, sometimes, inadequate reproductive counseling, particularly with respect to information about pursuing pregnancy. We identify four factors that might contribute to inadequate and inconsistent reproductive counseling. We argue that women with CKD should receive comprehensive reproductive counseling, including information about the possibility of pursuing pregnancy, and that more rigorous research on pregnancy in women with CKD, including women on dialysis or who have received a kidney transplant, is warranted to improve informed reproductive decision making in this population.

Consensus Definitions of BK Polyomavirus Nephropathy in Renal Transplant Recipients for Clinical Trials.

BACKGROUND: BK polyomavirus (BKPyV) infection and BK polyomavirus nephropathy (BKPyVAN) are important causes of allograft dysfunction and premature allograft loss in renal transplant recipients. RESULTS AND DISCUSSION: Controlled clinical trials to evaluate new agents for prevention and treatment are needed but are hampered by the lack of outcome measures that accurately assess the effect of the intervention, are clinically relevant, and are acceptable from a regulatory perspective. METHODS: To facilitate consistent end points in clinical trials and to support clinical research and drug development, definitions of BKPyV infection and disease have been developed by the BK Disease Definitions Working Group of the Transplantation Associated Virus Infection Forum with the Forum for Collaborative Research, which consists of scientists, clinicians, regulators, and industry representatives. CONCLUSIONS: These definitions refine established principles of "proven" BKPyV disease and introduce a "probable" disease category that could be used in clinical trials to prevent or treat BKPyVAN in renal transplant recipients.

A multi-institutional study of renal outcomes and renal-related pregnancy outcomes in uterus transplant recipients.

Uterus transplantation (UTx) is an effective treatment option for uterine factor infertility. However, the need for immunosuppression and congenital renal anomalies that coexist with uterine agenesis in about 30% of women with Mayer-Rokitansky-Kuster-Hauser syndrome create a risk for renal dysfunction. We therefore examined renal function trajectory and related pregnancy complications in an international cohort of 18 UTx recipients from September 2016-February 2020 who had at least one live birth. All UTx recipients had a diminution in their renal function that was apparent starting at 30 days posttransplant and in half the reduction in eGFR was at least 20%; the decrease in eGFR persisted into the early post-partum period. Half met criteria for Stage 1 acute kidney injury (AKI) as defined by the AKI Network criteria during their pregnancy. Overall, 28% of UTx recipients developed pre-eclampsia. eGFR was lower at embryo transfer and throughout pregnancy among those who developed pre-eclampsia, reaching statistical significance at week 16 of pregnancy. This effect was independent of tacrolimus levels. Mean eGFR remained significantly lower in the first 1-3 months after delivery. In the subgroup who reached 12 months of postpartum follow up and had a graft hysterectomy (n = 4), there was no longer a statistical difference in eGFR (pretransplant 106.7 ml/m ± 17.7 vs. 12 mos postpartum 92.6 ml/m ± 21.7, p = .13) but the number was small. Further study is required to delineate long term renal risks for UTx recipients, improve patient selection, and make decisions regarding a second pregnancy.

Management of cardiac diseases in liver transplant recipients: Comprehensive review and multidisciplinary practice-based recommendations.

Cardiac diseases are one of the most common causes of morbidity and mortality following liver transplantation (LT). Prior studies have shown that cardiac diseases affect close to one-third of liver transplant recipients (LTRs) long term and that their incidence has been on the rise. This rise is expected to continue as more patients with advanced age and/or non-alcoholic steatohepatitis undergo LT. In view of the increasing disease burden, a multidisciplinary initiative was developed to critically review the existing literature (between January 1, 1990 and March 17, 2021) surrounding epidemiology, risk assessment, and risk mitigation of coronary heart disease, arrhythmia, heart failure, and valvular heart disease and formulate practice-based recommendations accordingly. In this review, the expert panel emphasizes the importance of optimizing management of metabolic syndrome and its components in LTRs and highlights the cardioprotective potential for the newer diabetes medications (e.g., sodium glucose transporter-2 inhibitors) in this high-risk population. Tailoring the multidisciplinary management of cardiac diseases in LTRs to the cardiometabolic risk profile of the individual patient is critical. The review also outlines numerous knowledge gaps to pave the road for future research in this sphere with the ultimate goal of improving clinical outcomes.

Association of donor hepatitis C virus infection status and risk of BK polyomavirus viremia after kidney transplantation.

Kidney transplantation (KT) from deceased donors with hepatitis C virus (HCV) into HCV-negative recipients has become more common. However, the risk of complications such as BK polyomavirus (BKPyV) remains unknown. We assembled a retrospective cohort at four centers. We matched recipients of HCV-viremic kidneys to highly similar recipients of HCV-aviremic kidneys on established risk factors for BKPyV. To limit bias, matches were within the same center. The primary outcome was BKPyV viremia ≥1000 copies/ml or biopsy-proven BKPyV nephropathy; a secondary outcome was BKPyV viremia ≥10 000 copies/ml or nephropathy. Outcomes were analyzed using weighted and stratified Cox regression. The median days to peak BKPyV viremia level was 119 (IQR 87-182). HCV-viremic KT was not associated with increased risk of the primary BKPyV outcome (HR 1.26, p = .22), but was significantly associated with the secondary outcome of BKPyV ≥10 000 copies/ml (HR 1.69, p = .03). One-year eGFR was similar between the matched groups. Only one HCV-viremic kidney recipient had primary graft loss. In summary, HCV-viremic KT was not significantly associated with the primary outcome of BKPyV viremia, but the data suggested that donor HCV might elevate the risk of more severe BKPyV viremia ≥10 000 copies/ml. Nonetheless, one-year graft function for HCV-viremic recipients was reassuring.

Dialysis Nonadherence and Kidney Transplant Outcomes: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Concerns about nonadherent behaviors often prevent dialysis patients from entering waitlists for transplant even though there is an inconsistent association of these behaviors with posttransplant outcomes. We examined the association between plausible metrics of nonadherence related to dialysis treatment and posttransplant outcomes. STUDY DESIGN: Retrospective cohort. We linked national dialysis treatment data with transplant registry data. SETTING AND PARTICIPANTS: Adult patients receiving maintenance hemodialysis from January 1, 2004, through December 31, 2014, who received a kidney transplant at a US center. EXPOSURES: We examined 5 nonadherence metrics: serum potassium level (≥5.2 mEq/L), serum phosphorus level (>5.5 mg/dL), interdialytic weight gain (IDWG; ≥5 L), shortened treatments (≥30 min), and missed treatments (≥1); missed treatment data were available only for 2004-2009. These metrics were characterized per proportion of time under observation. Dialysis observation time was divided into 3-month intervals (quarters), and the number of nonadherent measurements in each domain was calculated for each quarter. OUTCOMES: Allograft loss, mortality, and acute rejection in the first posttransplant year. ANALYTICAL APPROACH: Using Cox proportional hazards and logistic regression, we estimated the hazard ratios for graft loss and mortality and odds ratios for rejection. RESULTS: 9,543 patients met inclusion criteria. In our primary model, hyperphosphatemia (adjusted hazard ratio [aHR], 1.27 [95% CI, 1.08-1.49]), large IDWG (aHR, 1.39 [95% CI, 1.23-1.59]), and shortened treatments (aHR, 1.54 [95% CI, 1.12-2.13]) were associated with greater rates of allograft loss, but hyperkalemia was not. Large IDWG (aHR, 1.49 [95% CI, 1.29-1.73]) and shortened treatments (aHR, 1.34 [95% CI, 1.13-1.58]) were associated with mortality, whereas hyperkalemia and hyperphosphatemia were not. Only shortened treatments were associated with an increased risk of acute rejection (adjusted odds ratio, 3.88 [95% CI, 1.98-7.58]). In models limited to the years 2004-2009 that included missed treatments, missed treatments were associated only with mortality. LIMITATIONS: Unmeasured confounding (eg, dietary data); adherence metrics used may have multiple, complex causes. CONCLUSIONS: Plausible measures of dialysis nonadherence have long-term associations with allograft and patient survival. Behavioral metrics were more closely associated with outcomes than laboratory markers were. The implications of nonadherent behaviors for dialysis patients must be carefully considered before patients are excluded from transplantation.

Acute kidney injury during pregnancy in kidney transplant recipients.

Pregnancy-related acute kidney injury (AKI) is a public health problem and remains an important cause of maternal and fetal morbidity and mortality. The incidence of pregnancy-related AKI has increased in developed countries due to increase in maternal age and higher detection rates. Pregnancy in women with kidney transplants is associated with higher adverse outcomes like preeclampsia, preterm births, and allograft dysfunction, but limited data exists on causes and outcomes of pregnancy-related AKI in the kidney transplant population. Diagnosis of AKI during pregnancy remains challenging in kidney transplant recipients due to lack of diagnostic criteria. Management of pregnancy-related AKI in the kidney transplant population requires a multidisciplinary team consisting of transplant nephrologists, high-risk obstetricians, and neonatologists. In this review, we discuss pregnancy-related AKI in women with kidney transplants, etiologies, pregnancy outcomes, and management strategies.

Tolerability of mycophenolate mofetil in elderly kidney transplant recipients: A retrospective cohort study.

BACKGROUND: Optimal immunosuppression in elderly kidney transplant recipients (KTRs) is not well defined, with mycophenolate mofetil (MMF) being poorly tolerated. Study aim was to compare MMF dose reduction incidence and reason(s) in elderly vs. nonelderly KTRs in the 1st year after transplant with a protocol dose of 1 g/day. METHODS: In this single-center retrospective study, first or repeat KTRs receiving rabbit antithymocyte globulin (rATG), MMF 1 g/day, tacrolimus, and prednisone, were stratified by age [≥60 (elderly) or <60 years (nonelderly)]. Primary outcome was MMF dose reduction incidence in the first year. Secondary outcomes included dose reduction rationale, 1-year patient and graft survival, graft function, rejection, infection, hospital presentation, and time to dose reduction. Of 335 KTRs, dose reduction incidence was significantly greater in the elderly group (66% and 54%, p = 0.04), though this did not remain significant when adjusted for sex, race, and valganciclovir use. Most common rationale was leukopenia in the elderly group and CMV in the nonelderly group. There were no significant differences in secondary outcomes. CONCLUSIONS: Mycophenolate mofetil 1 g/day was poorly tolerated in both elderly and nonelderly KTRs receiving lymphocyte-depleting induction with a high incidence of dose reductions; however, no short-term adverse graft outcomes were identified.

Sex and gender disparity in kidney transplantation: Historical and future perspectives.

Sex and gender disparity exist in various stages of kidney transplantation. Females were found to be less likely to be referred for kidney transplant, complete pre-transplant evaluation, be placed on the waitlist, and receive a kidney transplant compared to their male counterparts. Interestingly, females comprise the majority of living kidney donors. This review explores the biological and psychosocial factors that contribute to sex and gender disparity in kidney transplantation and proposes ways to address the disparity.

Impact of education on APOL1 testing attitudes among prospective living kidney donors.

It is unknown how providing prospective living donors with information about APOL1, including the benefits and drawbacks of testing, influences their desire for testing. In this study, we surveyed 102 participants with self-reported African ancestry and positive family history of kidney disease, recruited from our nephrology waiting room. We assessed views on APOL1 testing before and after presentation of a set of potential benefits and drawbacks of testing and quantified the self-reported level of influence individual benefits and drawbacks had on participants' desire for testing in the proposed context of living donation. The majority of participants (92%) were aware of organ donation and more than half (56%) had considered living donation. And though we found no significant change in response following presentation of the potential benefits and the drawbacks of APOL1 testing by study end significance, across all participants, "becoming aware of the potential risk of kidney disease among your immediate family" was the benefit with the highest mean influence (3.3±1.4), while the drawback with the highest mean influence (2.9±1.5) was "some transplant centers may not allow you to donate to a loved one". This study provides insights into the priorities of prospective living donors and suggests concern for how the information affects family members may strongly influence desires for testing. It also highlights the need for greater community engagement to gain a deeper understanding of the priorities that influence decision making on APOL1 testing.

Efficacy of hope: Analysis of organ quality and availability among deceased HIV-positive donors.

BACKGROUND: Improved survival among people with human immunodeficiency virus (HIV) (PWH) has led to increased organ failure, necessitating transplantation. In 2013, the HIV Organ Policy Equity (HOPE) Act was passed, allowing PWH to donate organs to other PWH. No study has assessed organ quality and quantity among a national pool of PWH. METHODS: CFAR Network of Integrated Clinical Systems (CNICS), a multicenter study capturing data on PWH, was used to identify 6504 deaths from 1999 to 2018. Exclusions included cause of death, chronic kidney disease, fibrosis-4 score ≥ 3.25, and opportunistic infection at the time of death. Donor quality was defined by HIV viremia and the kidney donor profile index (KDPI). The CDC Wonder database, which contains national death data, permitted the estimation of deaths among PWH nationally from 1999 to 2018. Assuming CNICS was representative of PWH nationally, percentages of potential donors were applied to the CDC Wonder cohort. RESULTS: Within CNICS, there were 3241 (65.9%) potential kidney donors and 3536 (71.9%) potential liver donors from 1999 to 2018. Based on viremia and KDPI, 821 were lower-risk kidney donors (16.7%) and 1206 (24.5%) were lower-risk liver donors. Within CDC Wonder, we identified 12 048 potential donors from 1999 to 2018. Extrapolating from CNICS to the national cohort suggested 396 kidney donors (792 kidneys) and 433 liver donors annually, with 100 kidney donors (200 kidneys) and 147 livers being lower-risk. CONCLUSION: A substantial number of PWH meet donation criteria, a valuable source of organs for PWH in need of transplants. Our estimates suggest there may be more available organs from PWH than current transplant numbers indicate.

Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement.

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.

Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement.

Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST-sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.

Analysis of malignant melanoma risk and outcomes in solid organ transplant recipients: Assessment of transplant candidacy and the potential role of checkpoint inhibitors.

Malignant melanoma (MM) causes tremendous morbidity and mortality in the solid organ transplant population and may arise in three different clinical scenarios: (1) pretransplant melanoma; (2) de novo melanoma post transplantation and (3) donor-derived melanoma. This manuscript primarily addresses the first two scenarios with respect to the evaluation and management of pretransplant MM, consideration of transplant candidacy and the occurrence and management of de novo MM post transplantation. The authors outline current evidence describing risks associated with pre-transplant melanoma to support recently established expert opinion for transplant candidacy.

Obesity is a risk factor for progression to kidney transplant waitlisting after liver transplantation.

BACKGROUND: Non-alcoholic steatohepatitis has emerged as a leading cause of cirrhosis, and obesity-associated comorbidities, including renal disease, have increased in prevalence. Obesity predisposes the kidney to hyperfiltration injury, potentially impairing acute kidney injury recovery. Identification of patients at risk for renal dysfunction is impeded by poor performance of renal function estimating equations among cirrhotics. To better understand obesity among cirrhotics and renal disease progression, we examined likelihood of kidney transplantation (KT) waitlisting after liver transplant alone (LTA) by obesity class. METHODS: 68 607 LTA recipients were identified in SRTR (2005-2018). Fine and Gray competing risks models were used to analyze likelihood of KT waitlisting. RESULTS: 27.4% of recipients were obese (BMI ≥ 30 kg/m2 ) and were 10% more likely to require KT waitlisting (aHR: 1.10, 95%CI: 1.01-1.20). Risk was highest among recipients with Classes II and III obesity (BMI: ≥35 kg/m2 ) (aHR: 1.37, 95%CI: 1.17-1.56). Moreover, recipients with Classes II and III obesity were 57% more likely to require KT waitlisting within one year post-LTA (aHR: 1.57, 95%CI: 1.18-2.10) compared to non-obese recipients. DISCUSSION: These findings suggest obesity was a risk factor for renal recovery failure and/or renal disease progression post-LTA and may confound identification of renal dysfunction and/or prediction of renal recovery among cirrhotics.