Non-invasive evaluation of hepatic macrosteatosis in deceased donors.

INTRODUCTION: Liver allocation changes have led to increased travel and expenditures, highlighting the need to efficiently identify marginal livers suitable for transplant. We evaluated the validity of existing non-invasive liver quality tests and a novel machine learning-based model at predicting deceased donor macrosteatosis >30%. METHODS: We compared previously-validated non-invasive tests and a novel machine learning-based model to biopsies in predicting macrosteatosis >30%. We also tested them in populations enriched for macrosteatosis. RESULTS: The Hepatic Steatosis Index area-under-the-curve (AUC) was 0.56. At the threshold identified by Youden's J statistic, sensitivity, specificity, positive, and negative predictive values were 49.6%, 58.9%, 14.0%, and 89.7%. Other tests demonstrated comparable results. Machine learning produced the highest AUC (0.71). Even in populations enriched for macrosteatosis, no test was sufficiently predictive. CONCLUSION: Commonly used clinical scoring systems and a novel machine learning-based model were not clinically useful, highlighting the importance of pre-procurement biopsies to facilitate allocation.

Reclassification of CKD in living kidney donors with the refitted race-free eGFR formula.

BACKGROUND: Chronic Kidney Disease (CKD) Epidemiology Collaboration eGFR 2021 formula removed Black race from the 2009 equation. Unintended consequences may lead to reclassifying Black living kidney donors as having more advanced CKD, exacerbating racial disparities in living donation. METHODS: We used national data to quantify CKD stage reclassification based on eGFR for Black living donors both pre- and post-donation. RESULTS: Among 6365 Black living donors, 17.7% were reclassified as having a higher CKD stage pre-donation with the 2021 formula. Among 4149 Black living donors with at least 2 creatinine measurements post-donation, 25.5% were reclassified as having a higher CKD stage post-donation with the 2021 formula. CONCLUSION: Eliminating race in the formula may inappropriately label Black potential donors with CKD. These data highlight the need for a validated eGFR formula for donors, use of measured and not eGFR, and education of non-transplant providers regarding interpretation of CKD staging in living donation.

Change in Body Mass Index and Attributable Risk of New-Onset Hypertension Among Obese Living Kidney Donors.

OBJECTIVE: To examine whether body mass index (BMI) changes modify the association between kidney donation and incident hypertension. BACKGROUND: Obesity increases hypertension risk in both general and living kidney donor (LKD) populations. Donation-attributable risk in the context of obesity, and whether weight change modifies that risk, is unknown. METHODS: Nested case-control study among 1558 adult LKDs (1976-2020) with obesity (median follow-up: 3.6 years; interquartile range: 2.0-9.4) and 3783 adults with obesity in the Coronary Artery Risk Development in Young Adults (CARDIA) and Atherosclerosis Risk in Communities (ARIC) studies (9.2 y; interquartile range: 5.3-15.8). Hypertension incidence was compared by donor status using conditional logistic regression, with BMI change investigated for effect modification. RESULTS: Overall, LKDs and nondonors had similar hypertension incidence [incidence rate ratio (IRR): 1.16, 95% confidence interval (95% CI): 0.94-1.43, P =0.16], even after adjusting for BMI change (IRR: 1.25, 95% CI: 0.99-1.58, P =0.05). Although LKDs and nondonors who lost >5% BMI had comparable hypertension incidence (IRR: 0.78, 95% CI: 0.46-1.34, P =0.36), there was a significant interaction between donor and >5% BMI gain (multiplicative interaction IRR: 1.62, 95% CI: 1.15-2.29, P =0.006; relative excess risk due to interaction: 0.90, 95% CI: 0.24-1.56, P =0.007), such that LKDs who gained weight had higher hypertension incidence than similar nondonors (IRR: 1.83, 95% CI: 1.32-2.53, P <0.001). CONCLUSIONS: Overall, LKDs and nondonors with obesity had similar hypertension incidence. Weight stability and loss were associated with similar hypertension incidence by donor status. However, LKDs who gained >5% saw increased hypertension incidence versus similar nondonors, providing support for counseling potential LKDs with obesity on weight management postdonation.

Diabetes-free survival among living kidney donors and non-donors with obesity: A longitudinal cohort study.

BACKGROUND: Approval of living kidney donors (LKD) with end-stage kidney disease (ESKD) risk factors, such as obesity, has increased. While lifetime ESKD development data are lacking, the study of intermediate outcomes such as diabetes is critical for LKD safety. Donation-attributable diabetes risk among persons with obesity remains unknown. The purpose of this study was to evaluate 10-year diabetes-free survival among LKDs and non-donors with obesity. METHODS: This longitudinal cohort study identified adult, LKDs (1976-2020) from 42 US transplant centers and non-donors from the Coronary Artery Risk Development in Young Adults (1985-1986) and the Atherosclerosis Risk in Communities (1987-1989) studies with body mass index ≥30 kg/m2. LKDs were matched to non-donors on baseline characteristics (age, sex, race, body mass index, systolic and diastolic blood pressure) plus diabetes-specific risk factors (family history of diabetes, impaired fasting glucose, smoking history). Accelerated failure time models were utilized to evaluate 10-year diabetes-free survival. FINDINGS: Among 3464 participants, 1119 (32%) were LKDs and 2345 (68%) were non-donors. After matching on baseline characteristics plus diabetes-specific risk factors, 4% (7/165) LKDs and 9% (15/165) non-donors developed diabetes (median follow-up time 8.5 (IQR: 5.6-10.0) and 9.1 (IQR: 5.9-10.0) years, respectively). While not significant, LKDs were estimated to live diabetes-free 2 times longer than non-donors (estimate 1.91; 95% CI: 0.79-4.64, p = 0.15). CONCLUSIONS: LKDs with obesity trended toward living longer diabetes-free than non-donors with obesity, suggesting within the decade following donation there was no increased diabetes risk among LKDs. Further work is needed to evaluate donation-attributable diabetes risk long-term.

COVID-19 Vaccination and Remdesivir are Associated With Protection From New or Increased Levels of Donor-Specific Antibodies Among Kidney Transplant Recipients Hospitalized With COVID-19.

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.

Perpetuating Disparity: Failure of the Kidney Transplant System to Provide the Most Kidney Transplants to Communities With the Greatest Need.

BACKGROUND: The burden of end-stage kidney disease (ESKD) and kidney transplant rates vary significantly across the United States. This study aims to examine the mismatch between ESKD burden and kidney transplant rates from a perspective of spatial epidemiology. METHODS: US Renal Data System data from 2015 to 2017 on incident ESKD and kidney transplants per 1000 incident ESKD cases was analyzed. Clustering of ESKD burden and kidney transplant rates at the county level was determined using local Moran's I and correlated to county health scores. Higher percentile county health scores indicated worse overall community health. RESULTS: Significant clusters of high-ESKD burden tended to coincide with clusters of low kidney transplant rates, and vice versa. The most common cluster type had high incident ESKD with low transplant rates (377 counties). Counties in these clusters had the lowest overall mean transplant rate (61.1), highest overall mean ESKD incidence (61.3), and highest mean county health scores percentile (80.9%, P <0.001 vs all other cluster types). By comparison, counties in clusters with low ESKD incidence and high transplant rates (n=359) had the highest mean transplant rate (110.6), the lowest mean ESKD incidence (28.9), and the lowest county health scores (20.2%). All comparisons to high-ESKD/low-transplant clusters were significant at P value <0.001. CONCLUSION: There was a significant mismatch between kidney transplant rates and ESKD burden, where areas with the greatest need had the lowest transplant rates. This pattern exacerbates pre-existing disparities, as disadvantaged high-ESKD regions already suffer from worse access to care and overall community health, as evidenced by the highest county health scores in the study.

Greater community vulnerability is associated with poor living donor navigator program fidelity.

BACKGROUND: Community-level factors contribute to living donor kidney transplantation disparities but may also influence the interventions aimed to mitigate these disparities. The Living Donor Navigator Program was designed to separate the advocacy role from the patient in need of transplantation-friends/family are encouraged to participate as the patients' advocates to identify living donors, though some of the patients participate alone as self-advocates. Self-advocates have a lower living donor kidney transplantation likelihood compared to the patients with an advocate. We sought to evaluate the relationship between the patients' community-level vulnerability and living donor navigator self-advocacy as a surrogate for program fidelity. METHODS: This single-center, retrospective study included 110 Living Donor Navigator participants (April 2017-June 2019). Program fidelity was assessed using the participants' advocacy status. Measures of community vulnerability were obtained from the Centers for Disease Control and Prevention Social Vulnerability Index. Modified Poisson regression was used to evaluate the association between community-level vulnerability and living donor navigator self-advocacy. RESULTS: Of the 110 participants, 19% (n = 21) were self-advocates. For every 10% increase in community-level vulnerability, patients had 17% higher risk of self-advocacy (adjusted relative risk 1.17, 95% confidence interval: 1.03-1.32, P = .01). Living in areas with greater unemployment (adjusted relative risk: 1.18, 95% confidence interval: 1.04-1.33, P = .01), single-parent households (adjusted relative risk: 1.23, 95% confidence interval: 1.06-1.42, P = .006), minority population (adjusted relative risk: 1.30, 95% confidence interval: 1.04-1.55, P = .02), or no-vehicle households (adjusted relative risk: 1.17, 95% confidence interval: 1.02-1.35, P = .02) were associated with increased risk of self-advocacy. CONCLUSION: Having a greater community-level vulnerability was associated with poor Living Donor Navigator Program fidelity. The potential barriers identified using the Social Vulnerability Index may direct resource allocation and program refinement to optimize program fidelity and efficacy for all participants.

Lost potential and missed opportunities for DCD liver transplantation in the United States.

BACKGROUND: Donation after cardiac death(DCD) has been proposed as an avenue to expand the liver donor pool. METHODS: We examined factors associated with nonrecovery of DCD livers using UNOS data from 2015 to 2019. RESULTS: There 265 non-recovered potential(NRP) DCD livers. Blood type AB (7.8% vs. 1.1%) and B (16.9% vs. 9.8%) were more frequent in the NRP versus actual donors (p < 0.001). The median driving time between donor hospital and transplant center was similar for NRP and actual donors (30.1 min vs. 30.0 min; p = 0.689), as was the percentage located within a transplant hospital (20.8% vs. 20.9%; p = 0.984).The donation service area(DSA) of a donor hospital explained 27.9% (p = 0.001) of the variability in whether a DCD liver was recovered. CONCLUSION: A number of potentially high quality DCD donor livers go unrecovered each year, which may be partially explained by donor blood type and variation in regional and DSA level practice patterns.

Abnormal time-zero histology is predictive of kidney transplant outcomes.

INTRODUCTION: Time-zero biopsies can detect donor-derived lesions at the time of kidney transplantation, but their utility in predicting long-term outcomes is unclear under the updated Kidney Allocation System. METHODS: We conducted a single-center retrospective cohort study of 272 consecutive post-reperfusion time-zero biopsies. We tested the hypothesis that abnormal time-zero histology is a strong indicator of donor quality that increases the precision of the kidney donor profile index (KDPI) score to predict long-term outcomes. RESULTS: We detected abnormal biopsies in 42% of the cohort, which were independently associated with a 1.2-fold increased hazard for a composite of acute rejection, allograft failure, and death after adjusting for clinical characteristics including KDPI. By Kaplan-Meier analysis, the relationship between abnormal time-zero histology and the composite endpoint was only significant in the subgroup of deceased donor kidney transplants with KDPI scores >35. Abnormal time-zero histology, particularly vascular intimal fibrosis and arteriolar hyalinosis scores, was independently associated with lower 12-month estimated GFR. CONCLUSION: In conclusion, abnormal time-zero histology is relatively common and identifies a group of kidney recipients at increased risk for worse long-term outcomes. Further studies are needed to determine the optimal patient population in which to deploy time-zero biopsies as an additional surveillance tool.

Hepatic macrosteatosis in the US pediatric deceased liver donor population.

INTRODUCTION: The pediatric obesity epidemic is associated with early development of hepatic macrosteatosis, a hallmark of non-alcoholic fatty LI disease, which is thought to be more rapidly progressive in children than adults. Macrosteatosis in adult allografts is associated with allograft loss, but this has not been examined in pediatric donors. METHODS: We studied all pediatric potential whole LI donors (2005-2018) who had a LI biopsy in the SRTR (n = 862) and whose LI was transplanted (n = 862). Macrosteatosis was abstracted from biopsy reports and compared to values in the SRTR standard analytic file. Recipients of macrosteatotic pediatric allografts were matched 1:1 to recipients of non-macrosteatotic pediatric allografts by propensity score matching on donor/recipient variables. All-cause allograft loss was estimated via Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: From 2005 to 2018, the proportion of pediatric donors (age ≥2 years) with obesity increased (14.8% to 21.7%; p < .001), as did the proportion of pediatric deceased whole LI-only donor allografts with macrosteatosis (n = 10 648; 1.8% to 3.9%; p < .001). The median degree of macrosteatosis among macrosteatotic donors was 10% (IQR 5-30). There were no significant differences in all-cause allograft loss between recipients of pediatric LI allografts with and without macrosteatosis at 90 days (p = .11) or 1 year (p = .14) post-transplant in Kaplan-Meier analysis or a Cox proportional hazards model (p > .05). CONCLUSION: Obese pediatric LI donors have increased over time and were more likely to have hepatic macrosteatosis; however, pediatric macrosteatosis did not appear to adversely affect recipient outcomes.

Liver Transplantation in Hepatitis B Reactivation in a Patient With Active HIV Viremia.

Acute hepatitis B virus infection is a common contraindication to liver transplantation surgery in the setting of active HIV viremia. This is a case report of a patient with decompensated cirrhosis and acute renal failure in the setting of hepatitis B virus reactivation and active HIV viremia who underwent liver transplantation with sustained graft survival.

Patient survival following third time liver transplant in the United States in the MELD era.

BACKGROUND: Third time liver transplantation is a technically demanding exercise with variable outcomes in single center series. There has been no national level description of survival following third time liver transplant in the US in the MELD era. METHODS: Third time liver transplants between March 1, 2002 and January 1, 2018 in the UNOS dataset were analyzed. RESULTS: Patient survival among the 240 third time liver transplant recipients in the study at 1, 3, 5, and 10 years (71.8%, 62.4%, 59.1%, 49.5%) was significantly worse compared to primary liver transplant (90.6%, 83.9%, 78.8%, 67.6%; p < 0.001) and retransplant (77.1%, 70.3%, 65.6%, 54.9%; p = 0.014). Recipients who were under 43 years old, not on dialysis, without diabetes, and over 1 month out from their second transplant had acceptable survival at 1, 3, 5, and 10 years (88.5%, 78.4%, 73.6%, 69.7%). CONCLUSIONS: While redo-redo transplant remains a challenging endeavor, appropriate patient selection can yield acceptable results.

Evaluation of Community-Level Vulnerability and Racial Disparities in Living Donor Kidney Transplant.

Importance: Living donor kidney transplant (LDKT) is the ideal treatment for end-stage kidney disease, but racial disparities in LDKT have increased over the last 2 decades. Recipient clinical and social factors do not account for LDKT racial inequities, although comprehensive measures of community-level vulnerability have not been assessed. Objective: To determine if racial disparities persist in LDKT independent of community-level vulnerability. Design, Setting, and Participants: This retrospective, multicenter, cross-sectional study included data from 19 287 adult kidney-only transplant recipients in the Scientific Registry of Transplant Recipients. The study included individuals who underwent transplant between January 1 and December 31, 2018. Exposures: Recipient race and the 2018 US Centers for Disease Control and Prevention Social Vulnerability Index (SVI). Census tract-level SVI data were linked to census tracts within each recipient zip code. The median SVI measure among the census tracts within a zip code was used to describe community-level vulnerability. Main Outcomes and Measures: Kidney transplant donor type (deceased vs living). Modified Poisson regression was used to evaluate the association between SVI and LDKT, and to estimate LDKT likelihood among races, independent of community-level vulnerability and recipient-level characteristics. Results: Among 19 287 kidney transplant recipients, 6080 (32%) received LDKT. A total of 11 582 (60%) were male, and the median (interquartile range) age was 54 (43-63) years. There were 760 Black LDKT recipients (13%), 4865 White LDKT recipients (80%), and 455 LDKT recipients of other races (7%; American Indian, Asian, multiracial, and Pacific Islander). Recipients who lived in communities with higher SVI (ie, more vulnerable) had lower likelihood of LDKT compared with recipients who lived in communities with lower SVI (ie, less vulnerable) (adjusted relative risk [aRR], 0.97; 95% CI, 0.96-0.98; P < .001). Independent of community-level vulnerability, compared with White recipients, Black recipients had 37% lower likelihood (aRR, 0.63; 95% CI, 0.59-0.67; P < .001) and recipients of other races had 24% lower likelihood (aRR, 0.76; 95% CI, 0.70-0.82; P < .001) of LDKT. The interaction between SVI and race was significant among Black recipients, such that the disparity in LDKT between Black and White recipients increased with greater community-level vulnerability (ratio of aRRs, 0.67; 95% CI, 0.51-0.87; P = .003). Conclusions and Relevance: Community-level vulnerability is associated with access to LDKT but only partially explains LDKT racial disparities. The adverse effects of living in more vulnerable communities were worse for Black recipients. The interaction of these constructs is worrisome and suggests evaluation of other health system factors that may contribute to LDKT racial disparities is needed.

Survival following simultaneous liver-lung versus liver alone transplantation: Results of the US national experience.

BACKGROUND: There are little data to compare the post-transplant survival between lung-liver transplant (LLT) and liver-alone recipients. This study was undertaken to compare survival between LLT and liver-alone transplant. METHODS: UNOS data for patients undergoing LLT from 2002 to 2017 was analyzed. LLT recipients (n = 81) were matched 1:4 to liver-alone recipients (n = 324) by propensity score and patient survival was compared in the matched cohorts. RESULTS: Unadjusted 1, 3, and 5-year patient survival in the matched cohort was significantly worse in the LLT (82.5%, 72.2%, and 62.2%) versus liver-alone (92.2%, 82.8%, and 80.9%; p = 0.005). This difference persisted after adjusting for covariates with residual imbalance (HR 2.05, 95% CI 1.37-3.08; p = 0.001). CONCLUSION: LLT has significantly worse survival than liver-alone transplant. With an increasing organ shortage, medical necessity criteria such as those developed for simultaneous liver-kidney transplantation should be developed for simultaneous lung-liver transplants to assure liver allografts are only allocated when truly needed.

Self-advocacy is associated with lower likelihood of living donor kidney transplantation.

BACKGROUND: The Living Donor Navigator (LDN) Program pairs kidney transplant candidates (TC) with a friend or family member for advocacy training to help identify donors and achieve living donor kidney transplantation (LDKT). However, some TCs participate alone as self-advocates. METHODS: In this retrospective cohort study of TCs in the LDN program (04/2017-06/2019), we evaluated the likelihood of LDKT using Cox proportional hazards regression and rate of donor screenings using ordered events conditional models by advocate type. RESULTS: Self-advocates (25/127) had lower likelihood of LDKT compared to patients with an advocate (adjusted hazard ratio (aHR): 0.22, 95% confidence interval (CI): 0.03-1.66, p = 0.14). After LDN enrollment, rate of donor screenings increased 2.5-fold for self-advocates (aHR: 2.48, 95%CI: 1.26-4.90, p = 0.009) and 3.4-fold for TCs with an advocate (aHR: 3.39, 95%CI: 2.20-5.24, p < 0.0001). CONCLUSIONS: Advocacy training was beneficial for self-advocates, but having an independent advocate may increase the likelihood of LDKT.

Acute Liver Failure in a Healthy Young Female With COVID-19.

Several well-described manifestations of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. Among them, a transient elevation of liver enzymes is the typical presentation of coronavirus disease 2019 (COVID-19) liver-related injury. The mechanism of liver involvement is likely a combination of viral injury and immune-mediated inflammation. In contrast, acute liver failure in the setting of COVID-19 has rarely been reported. Herein, we report a case of pediatric acute liver failure in a previously healthy female adolescent infected with SARS-CoV-2 with biopsy evidence of replicating virus in hepatocytes, which has not been previously reported.

Bariatric surgery to achieve transplant in end-stage organ disease patients: A systematic review and meta-analysis.

BACKGROUND: As obesity prevalence grows, more end-stage organ disease patients will be precluded from transplant. Numerous reports suggest bariatric surgery in end-stage organ disease may help patients achieve weight loss sufficient for transplant listing. METHODS: We performed a systematic review/meta-analysis of studies of bariatric surgery to achieve solid organ transplant listing. RESULTS: Among 82 heart failure patients, 40.2% lost sufficient weight for listing, 29.3% were transplanted, and 8.5% had sufficient improvement with weight loss they no longer required transplantation. Among 28 end-stage lung disease patients, 28.6% lost sufficient weight for listing, 7.1% were transplanted, and 14.3% had sufficient improvement following weight loss they no longer required transplant. Among 41 cirrhosis patients, 58.5% lost sufficient weight for listing, 41.5% were transplanted, and 21.9% had sufficient improvement following weight loss they no longer required transplant. Among 288 end-stage/chronic kidney disease patients, 50.3% lost sufficient weight for listing and 29.5% were transplanted. CONCLUSIONS: Small sample size and publication bias are limitations; however, bariatric surgery may benefit select end-stage organ disease patients with obesity that precludes transplant candidacy.

Donation approval among obese living kidney donor candidates: The impact of metabolic syndrome.

BACKGROUND: The scarcity of organs available for transplantation has increased attempts to augment transplantation by utilizing obese living kidney donors. The literature has suggested that these donors have increased risks postdonation. Not surprising, the threshold for living kidney donor approval among obese persons is typically higher and the process more costly. Therefore, a screening tool to predict the likelihood of approval among obese living kidney donor candidates was created. METHODS: A single-center retrospective study was performed among obese (body mass index ≥ 30 kg/m2) living kidney donor candidates evaluated in clinic (January 1, 2012, to December 31, 2017). Approved candidates were compared with those not approved using multivariable logistic regression, and a prediction tool was generated. RESULTS: Among 389 obese living kidney donor candidates, there were no significant differences in sex or race and ethnicity by approval status. However, nonapproved candidates had a higher prevalence of metabolic syndrome. In the prediction model, glucose impairment and hypertension were most predictive of nonapproval. CONCLUSION: Among obese living kidney donor candidates, several metabolic syndrome components were associated with decreased odds of approval. This tool may serve as a useful initial screening for obese living kidney donor candidates, permitting more cost-effective evaluation processes. The tool could also be used to promote expeditious interventions in the preclinical setting, including weight management programs, to improve the likelihood of donation and postdonation outcomes.