Faculty Bibliography

Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter wait list times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated to receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+R- had excellent graft function with a mean follow up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, re-operation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV negative pancreas allografts were transplanted, compared to only 5% of ideal HCV positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV positive pancreata for HCV naïve recipients and advocates for increased utilization of ideal HCV positive pancreas allografts.

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.

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.77 1.40_2.56 ,P = .3) and moderately (wIRR = _0.88 1.35_2.06 ,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.33 2.22_3.72 ,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.62 3.57_4.88 , P < .001) and death-censored graft loss (wHR = _1.15 4.01_13.95 ,P = .03). Post-KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.

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.

BACKGROUND:The Lung Allocation Score (LAS) significantly improved outcomes and waitlist mortality in lung transplantation. However, mortality remains high for the sickest waitlist candidates despite additional changes to allocation distance. Regulatory considerations of overhauling the current lung allocation system has met significant resistance, and would require years to implement. This study evaluates if a modest change to the current system by prioritization of only high-LAS lung transplant candidates would result in lowered waitlist mortality. METHODS:The Thoracic Simulated Allocation Model was used to evaluate all lung transplant candidates and donor lungs recovered between July 1, 2009 and June 30, 2011. Current lung allocation rules (initial offer within 250 nautical-mile radius for ABO-identical then compatible offers) were run. Allocation was then changed for only patients with an LAS≥50 (high-LAS) to be prioritized within a 500 nautical-mile radius with no stratification between ABO-identical and compatible offers. Ten iterations of each model were run. Primary endpoints were waitlist mortality and post-transplant 1-year survival. RESULTS:6,538 waitlist candidates and transplant recipients were evaluated per iteration, for a total of 130,760 simulated patients. Compared with current allocation, the adjusted model had a 23.3% decrease in waitlist mortality. Post-transplant 1-year survival was minimally affected. CONCLUSIONS:Without overhauling the entire system, simple prioritization changes to the allocation system for high-LAS candidates may lead to decreased waitlist mortality and increased organ utilization. Importantly, these changes do not appear to lead to clinically significant changes in post-transplant 1-year survival.

BACKGROUND:Coronavirus disease 2019 (Covid-19) remains a worldwide pandemic with a high mortality rate among patients requiring mechanical ventilation. The limited data that exists regarding the utility of extracorporeal membrane oxygenation (ECMO) in these critically ill patients shows poor overall outcomes. This paper describes our institutional practice regarding the application and management of ECMO support for patients with Covid-19 and reports promising early outcomes. METHODS:>60 mmHg with no life-limiting comorbidities. Patients were cannulated at bedside and were managed with protective lung ventilation, early tracheostomy, bronchoscopies and proning as clinically indicated. RESULTS:Of 321 patients intubated for Covid-19, 77 (24%) patients were evaluated for ECMO support with 27 (8.4%) patients placed on ECMO. All patients were placed on veno-venous ECMO. Current survival is 96.3%, with only one mortality to date in over 350 days of total ECMO support. Thirteen patients (48.1%) remain on ECMO support, while 13 patients (48.1%) have been successfully decannulated. Seven patients (25.9%) have been discharged from the hospital. Six patients (22.2%) remain in the hospital of which four are on room-air. No healthcare workers that participated in ECMO cannulation developed symptoms of or tested positive for Covid-19. CONCLUSIONS:The early outcomes presented here suggest that the judicious use of ECMO support in severe Covid-19 may be clinically beneficial.

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

RATIONALE AND OBJECTIVE/OBJECTIVE:Compared to recipients of ABO-compatible (ABOc) living donor kidney transplants (LDKT), recipients of ABO-incompatible (ABOi) LDKT have a higher risk of graft loss, particularly in the first few weeks after transplantation. However, the decision to proceed with ABOi LDKT should be based on a comparison of the alternative: waiting for future ABOc LDKT (e.g, through kidney paired exchange) or for a deceased donor kidney transplant (DDKT). We sought to evaluate the patient survival difference between ABOi LDKT and waiting for an ABOc LDKT or an ABOc DDKT. STUDY DESIGN/METHODS:Retrospective cohort study of adults in the Scientific Registry of Transplant Recipients (SRTR) SETTING AND PARTICIPANTS: 808 ABOi LDKT recipients and 2423 matched controls from among 245,158 adult, first-time kidney-only waitlist registrants who did not receive an ABOi LDKT and who remained on the waitlist or received either an ABOc LDKT or an ABOc DDKT, 2002-2017 EXPOSURE: Receipt of ABOi LDKT OUTCOME: Death ANALYTICAL APPROACH: We compared mortality among ABOi LDKT recipients versus a weighted matched comparison population using Cox proportional hazards regression as well as Cox models that accommodated for changing hazards ratios over time. RESULTS:Compared to matched controls, ABOi LDKT was associated with lower survival risk in the first 30 days post-transplant (99.0% vs 99.6%, respectively), but higher survival risk beyond 180 days post-transplant. Patients who received ABOi LDKT had higher survival at 5 and 10 years (90.0% and 75.4% respectively) than similar patients who remained on the waitlist or received ABOc LDKT or ABOc DDKT (81.9% and 68.4% respectively). LIMITATIONS/CONCLUSIONS:No measurement of ABO antibody titers in recipients; eligibility of participants for kidney paired donation is unknown. CONCLUSIONS:Transplant candidates who receive an ABOi LDKT and survive more than 180 days post-transplant experience a long-term survival benefit compared to remaining on the waitlist to potentially receive an ABO compatible kidney transplant.

To determine the impact of tocilizumab, a monoclonal antibody against the interleukin 6 receptor, on survival in patients with coronavirus disease 2019.