Kidney Transplantation in the Immunologically High-Risk Patient

Survival for dialysis patients is dismal. They have an adjusted mortality rate 6.5-7.9 times higher than the general population. Kidney transplant (KT) recipients enjoy significant survival and quality of life advantages compared to remaining dialysis-dependent (1-5). Unfortunately, kidney demand far exceeds supply, with over 90,000 on the wait list (5). Highly sensitized patients constitute an increasingly large part of the wait list (6). Advancements in desensitization have allowed for KT across previously insurmountable immunological barriers; however, incompatible live donor kidney transplantation (ILDKT) is in its nascency and the literature is limited by single-center data, small sample sizes, and publication bias. ILDKT risks are generally considered to be higher than for compatible KT, but these risks have never been quantified precisely. Chapter 2 does precisely this using primary data collected from 22 U.S. transplant centers, constituting the largest cohort of ILDKT patients in existence. ILDKT risks are not limited to recipients. The federal government provides strict oversight of transplant outcomes. Chapter 2 quantifies the regulatory risk centers assume when they transplant immunologically high-risk patients. IKT patients are also at elevated risk of antibody-mediated rejection (AMR), which mediates much of the graft loss in ILDKT. Chapter 3 details the formation of the world's largest cohort of AMR patients, defined using strict clinical, pathological, and immunologic criteria, and quantification of the risk of graft loss associated with AMR by transplant type. There exists an uncommon, but virulent phenotype of AMR in ILDKT patients that is rapid in onset, severe in the graft dysfunction it causes, difficult to treat, and immediately graft-threatening without prompt action. Chapter 4 describes these patients in detail and compares the early rescue rate and impact of the severe AMR episode on the development of transplant glomerulopathy between salvage modalities, offering novel insight into the management of this challenging and devastating ILDKT complication. Overall, this dissertation explores the risk of ILDKT to patients and centers, and delves into particular aspects of AMR within the context of ILDKT

Early Kidney Allograft Failure After Simultaneous Liver-kidney Transplantation: Evidence for Utilization of the Safety Net?

BackgroundWith 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).MethodsAn 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.ResultsOf 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).ConclusionsAs 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

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

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. 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. 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). 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. •There are no current criteria to guide allocation of lung-liver transplants.•Lung-liver recipients often have compensated liver disease with a low MELD score.•Survival after lung-liver transplant is inferior to that after liver transplant alone.•Necessity criteria are needed to ensure liver-lung transplants are truly warranted

County-level Differences in Liver-related Mortality, Waitlisting, and Liver Transplantation in the United States

Background. Much of our understanding regarding geographic issues in transplantation is based on statistical techniques that do not formally account for geography and is based on obsolete boundaries such as donation service area. Methods. We applied spatial epidemiological techniques to analyze liver-related mortality and access to liver transplant services at the county level using data from the Centers for Disease Control and Prevention and Scientific Registry of Transplant Recipients from 2010 to 2018. Results. There was a significant negative spatial correlation between transplant rates and liver-related mortality at the county level (Moran's I, -0.319; P = 0.001). Significant clusters were identified with high transplant rates and low liver-related mortality. Counties in geographic clusters with high ratios of liver transplants to liver-related deaths had more liver transplant centers within 150 nautical miles (6.7 versus 3.6 centers; P < 0.001) compared with all other counties, as did counties in geographic clusters with high ratios of waitlist additions to liver-related deaths (8.5 versus 2.5 centers; P < 0.001). The spatial correlation between waitlist mortality and overall liver-related mortality was positive (Moran's I, 0.060; P = 0.001) but weaker. Several areas with high waitlist mortality had some of the lowest overall liver-related mortality in the country. Conclusions. These data suggest that high waitlist mortality and allocation model for end-stage liver disease do not necessarily correlate with decreased access to transplant, whereas local transplant center density is associated with better access to waitlisting and transplant

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

Donation after cardiac death(DCD) has been proposed as an avenue to expand the liver donor pool. We examined factors associated with nonrecovery of DCD livers using UNOS data from 2015 to 2019. 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. 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. •A significant number of potentially high quality DCD livers go unrecovered.•Non-recovery of DCD livers is not associated with travel distance for recovery.•Local practices may explain a significant percentage of why DCD livers go unrecovered