Faculty Bibliography

OBJECTIVE:The aim of this study was to characterize end-stage renal disease (ESRD) patients with obesity as their only contraindication to listing and to quantify wait-list and transplant access. METHODS:Using the US Renal Data System, a retrospective cohort study of incident dialysis cases (2012 to 2014) was performed. The primary outcomes were time to wait-listing and time to transplantation. RESULTS:Of 157,572 dialysis patients not already listed, 39,844 had BMI as their only demonstrable transplant contraindication. They tended to be younger, female, and Black. Compared with patients with BMI < 35, those with BMI 35 to 39.9, 40 to 44.9, and ≥45 were, respectively, 15% (adjusted hazard ratio [aHR] 0.85; 95% CI: 0.83-0.88; p < 0.001), 45% (aHR 0.55; 95% CI: 0.52-0.57; p < 0.001), and 71% (aHR 0.29; 95% CI: 0.27-0.31; p < 0.001) less likely to be wait-listed. Wait-listed patients with BMI 35 to 39.9 were 24% less likely to achieve transplant (aHR 0.76; 95% CI: 0.72-0.80; p < 0.0001), BMI 40 to 44.9 were 21% less likely (aHR 0.79; 95% CI: 0.72-0.86; p < 0.0001), and BMI ≥ 45 were 15% less likely (aHR 0.85; 95% CI: 0.75-0.95; p = 0.004) compared with patients with BMI < 35. CONCLUSIONS:Obesity was the sole contraindication to wait-listing for 40,000 dialysis patients. They were less likely to be wait-listed. For those who were, they had a lower likelihood of transplant. Aggressive weight-loss interventions may help this population achieve wait-listing and transplant.

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.

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.

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:) (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.

BACKGROUND:A safety net policy was implemented in August 2017 giving liver transplant alone (LTA) recipients with significant renal dysfunction posttransplant priority for subsequent kidney transplantation (KT). This study was undertaken to evaluate early outcomes under this policy. METHODS:Adults undergoing LTA after implementation of the safety net policy and were subsequently listed for KT between 60 and 365 days after liver transplantation contained in United Network for Organ Sharing data were examined. Outcomes of interest were receipt of a kidney transplant and postliver transplant survival. Safety net patients were compared with LTA recipients not subsequently listed for KT as well as to patients listed for simultaneous liver-kidney (SLK) transplant yet underwent LTA and were not subsequently listed for KT. RESULTS:There were 100 patients listed for safety net KT versus 9458 patients undergoing LTA without subsequent KT listing. The cumulative incidence of KT following listing was 32.5% at 180 days. The safety net patients had similar 1-year unadjusted patient survival (96.4% versus 93.4%; P = 0.234) but superior adjusted survival (hazard ratio0.133, 0.3570.960; P = 0.041) versus LTA recipients not subsequently listed for KT. Safety net patients had superior 1-year unadjusted (96.4% versus 75.0%; P < 0.001) and adjusted (hazard ratio0.039, 0.1260.406; P < 0.001) survival versus SLK listed patients undergoing LTA without subsequent KT listing. CONCLUSIONS:The safety net appears to provide rapid access to KT with good early survival for those able to take advantage of it. Survival of patients unable to qualify for KT listing after LTA needs to be better understood before further limitation of SLK, however.

BACKGROUND:With the implementation of the "Safety Net," we aimed to determine the impact of simultaneous liver-kidney transplantation (SLKT), as compared to kidney transplant after liver transplant (KALT), on kidney allograft failure (KF). METHODS:An analysis of the UNOS database for all adult patients who received either an SLKT or KALT from 2002 to 2017. The outcomes were 90-day KF and 1-year KF (as reported to UNOS, at 90- and 365-day postkidney transplant, respectively). We compared the following groups of patients: SLKT <25 (SLKT with final model for end-stage liver disease [MELD] <25), SLKT25/35 (MELD ≥25/<35), and SLKT35 (MELD ≥35) to KALT. RESULTS:Of the 6276 patients, there were 1481 KALT, 1579 SLKT <25, 1832 SLKT25/35, and 1384 SLKT ≥35. The proportion of patients with 90-day and 1-year KF increased significantly among the KALT, SLKT <25, SLKT25/35, and SLKT ≥35 groups (P < 0.001; test for trend): 90-day KF: 3.3% versus 5.5% versus 7.3% versus 9.3% and 1-year KF: 5.1% versus 9.4% versus 12.3% versus 14.7%. After adjustment and compared with KALT, beginning at an MELD ≥25 those undergoing SLKT had significantly higher risk of 90-day and 1-year KF: 90-day KF: SLKT25/35: hazard ratio, 1.6(1.0-2.3); SLKT ≥35: 2.1(1.3-3.3); 1-year KF: SLKT25/35: hazard ratio, 1.7(1.2-2.4); SLKT ≥35: 2.1(1.5-3.0). CONCLUSIONS:As compared to KALT recipients, SLKT recipients with an MELD ≥25 had significantly higher risk of early KF. Given the now well-established "Safety Net," KALT may serve as an opportunity to improve kidney outcomes in patients with an MELD ≥25.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = _1.03 1.68_2.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = _1.45 2.09_3.02 ; PFNC = _1.67 2.40_3.46 ; PCC = _1.48 2.24_3.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = _1.34 1.62_1.95 ) than CLDKT (aHR = _1.96 2.29_2.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

BACKGROUND:Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remain unknown. METHODS:We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to SRTR for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences, and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS:After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (p<0.01) and 4.4% of the differences in graft loss (p<0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSION/CONCLUSIONS:Unlike most aspects of transplantation where center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.