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Background: Outcomes after living-donor liver transplantation (LDLT) at high Model for End-stage Liver Disease (MELD) scores are not well characterized in the United States., Methods: This was a retrospective cohort study using Organ Procurement and Transplantation Network data in adults listed for their first liver transplant alone between 2002 and 2021. Cox proportional hazards models evaluated the association of MELD score (<20, 20-24, 25-29, and ≥30) and patient/graft survival after LDLT and the association of donor type (living versus deceased) on outcomes stratified by MELD., Results: There were 4495 LDLTs included with 5.9% at MELD 25-29 and 1.9% at MELD ≥30. LDLTs at MELD 25-29 and ≥30 LDLT have substantially increased since 2010 and 2015, respectively. Patient survival at MELD ≥30 was not different versus MELD <20: adjusted hazard ratio 1.67 (95% confidence interval, 0.96-2.88). However, graft survival was worse: adjusted hazard ratio (aHR) 1.69 (95% confidence interval, 1.07-2.68). Compared with deceased-donor liver transplant, LDLT led to superior patient survival at MELD <20 (aHR 0.92; P = 0.024) and 20-24 (aHR 0.70; P < 0.001), equivalent patient survival at MELD 25-29 (aHR 0.97; P = 0.843), but worse graft survival at MELD ≥30 (aHR 1.68, P = 0.009)., Conclusions: Although patient survival remains acceptable, the benefits of LDLT may be lost at MELD ≥30., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Prior studies are inconsistent regarding the impact of antibody induction therapy on outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC)., Methods: Adults transplanted with HCC exception priority were identified from February 27, 2002, to March 31, 2019, using the United Network for Organ Sharing database. Time-to-event analyses evaluated the association of antibody induction therapy (none, nondepleting induction [NDI], depleting induction [DI]) with overall post-LT patient survival and HCC recurrence. Separate multivariable models adjusted for tumor characteristics on either last exception or on explant. The interaction of induction and maintenance regimen at LT discharge was investigated., Results: Among 22 535 LTs for HCC, 17 688 (78.48%) received no antibody induction, 2984 (13.24%) NDI, and 1863 (8.27%) DI. Minimal differences in patient and tumor characteristics were noted between induction groups, and there was significant center variability in practices. NDI was associated with improved survival, particularly when combined with a calcineurin inhibitor (CNI) and antimetabolite (hazard ratio [HR] 0.73 versus no induction plus 3-drug therapy in the last exception model [ P  < 0.001]; HR 0.64 in the explant model [ P  = 0.011]). The combination of DI with CNI alone was also protective (HR 0.43; P  = 0.003). Neither NDI nor DI was associated with tumor recurrence (all P  > 0.1). However, increased HCC recurrence was observed with no induction plus CNI monotherapy (HR 1.47, P  = 0.019; versus no induction plus 3-drug therapy)., Conclusions: In conclusion, induction immunosuppression was not associated with worse post-LT outcomes in patients transplanted with HCC exception priority. An improvement in survival was possibly observed with NDI., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The Kidney Donor Risk Index (KDRI) is a score applicable to deceased kidney donors which reflects relative graft failure risk associated with deceased donor characteristics. The KDRI is widely used in kidney transplant outcomes research. Moreover, an abbreviated version of KDRI is the basis, for allocation purposes, of the "top 20%" designation for deceased donor kidneys. Data upon which the KDRI model was based used kidney transplants performed between 1995 and 2005. Our purpose in this report was to evaluate the need to update the coefficients in the KDRI formula, with the objective of either (a) proposing new coefficients or (b) endorsing continued used of the existing formula., Methods: Using data obtained from the Scientific Registry of Transplant Recipients, we analyzed n = 156069 deceased donor adult kidney transplants occurring from 2000 to 2016. Cox regression was used to model the risk of graft failure. We then tested for differences between the original and updated regression coefficients and compared the performance of the original and updated KDRI formulas with respect to discrimination and predictive accuracy., Results: In testing for equality between the original and updated KDRIs, few coefficients were significantly different. Moreover, the original and updated KDRI yielded very similar risk discrimination and predictive accuracy., Conclusions: Overall, our results indicate that the original KDRI is robust and is not meaningfully improved by an update derived through modeling analogous to that originally employed.

Background: We examined the association of incident end-stage renal disease (ESRD) after liver transplantation (LT) and resource utilization using a data linkage between the Scientific Registry of Transplant Recipients and claims data from the Centers for Medicare and Medicaid Services., Methods: The study cohort consisted of patients aged ≥18 years who underwent deceased donor LT between January 1, 2003, and December 31, 2010, with Medicare as primary or secondary insurance and were discharged alive from the index LT hospitalization (n = 7019). The association of ESRD and post-LT hospitalization was assessed by sequential stratification, which entailed prognostic score matching of ESRD-free patients to each LT recipient at ESRD onset. The prognostic score was developed from a model of time to hospitalization and included baseline factors and hospitalization history as predictors., Results: The overall hospitalization rates for LT recipients with and without ESRD were 2.7 and 1.1 per patient-year at risk, respectively. The total number of days hospitalized patient per year was 23 in ESRD and 7 in non-ESRD LT recipients. The adjusted post-LT hospitalization rate was 97% higher after reaching ESRD compared to non-ESRD (hazard ratio, 1.97; P < 0.0001)., Conclusions: Hospitalization rates increased significantly for LT recipients after ESRD onset. Early risk factor modification efforts targeting patients who are at high ESRD risk may reduce post-LT ESRD incidence and hence decrease morbidity and cost among LT recipients.

Background: Simultaneous kidney and pancreas (SPK) transplantation is an attractive option for end-stage renal disease patients with type 1 diabetes. Although SPK transplantation is superior to remaining on dialysis, the survival advantage for SPK recipients compared to kidney transplantation alone (KTA) is controversial., Methods: Using data obtained from the Scientific Registry of Transplant Recipients, we compared patient and graft survivals for 7308 SPK and 4653 KTA adult patients with type I diabetes transplanted in 1998 to 2009. Because SPK and KTA recipients are differently selected, comparison groups were chosen to maximize overlap in the case mixes. Most previous studies contrasted (unadjusted) Kaplan-Meier survival curves or, if covariate-adjusted, reported hazard ratios (HRs). Using newer statistical methods, we avoid relying on hazard ratios (which are seldom of inherent interest) and directly compare covariate-adjusted survival curves. Specifically, we compare average covariate-adjusted SPK- and KTA-specific survival curves (and 10-year area under the curve; ie, restricted mean survival time) to emulate a randomized clinical trial., Results: Mean restricted mean kidney graft survival time was significantly greater by 0.18 years (P = 0.045) for SPK compared to KTA. Similarly, patient survival was 0.17 years greater (P = 0.033) for SPK than KTA. Increased graft survival was primarily observed in younger SPK recipients. Supplementary analysis revealed that the SPK hazards were nonproportional, meaning that it would be difficult to quantify the cumulative effect of SPK through a standard Cox regression analysis., Conclusions: Using this novel methodology, we demonstrate that SPK is associated with statistically but not clinically significant increases in graft and patient survival.

Background: We aimed to examine the association between recipient race/ethnicity and sex, donor liver quality, and liver transplant graft survival., Methods: Adult non-status 1 liver recipients transplanted between March 1, 2002, and December 31, 2008, were identified using Scientific Registry of Transplant Recipients data. The factors of interest were recipient race/ethnicity and sex. Donor risk index (DRI) was used as a donor quality measure. Logistic regression was used to assess the association between race/ethnicity and sex in relation to the transplantation of low-quality (high DRI) or high-quality (low DRI) livers. Cox regression was used to assess the association between race/ethnicity and sex and liver graft failure risk, accounting for DRI., Results: Hispanics were 21% more likely to receive low-quality grafts compared to whites (odds ratio [OR]=1.21, P=0.002). Women had greater odds of receiving a low-quality graft compared to men (OR=1.24, P<0.0001). Despite adjustment for donor quality, African American recipients still had higher graft failure rates compared to whites (hazard ratio [HR]=1.28, P<0.001). Hispanics (HR=0.89, P=0.023) had significantly lower graft failure rates compared to whites despite higher odds of receiving a higher DRI graft. Using an interaction model of DRI and race/ethnicity, we found that the impact of DRI on graft failure rates was significantly reduced for African Americans compared to whites (P=0.02)., Conclusions: This study shows that while liver graft quality differed significantly by recipient race/ethnicity and sex, donor selection practices do not seem to be the dominant factor responsible for worse liver transplant outcomes for minority recipients.

Background: We propose a continuous kidney donor risk index (KDRI) for deceased donor kidneys, combining donor and transplant variables to quantify graft failure risk., Methods: By using national data from 1995 to 2005, we analyzed 69,440 first-time, kidney-only, deceased donor adult transplants. Cox regression was used to model the risk of death or graft loss, based on donor and transplant factors, adjusting for recipient factors. The proposed KDRI includes 14 donor and transplant factors, each found to be independently associated with graft failure or death: donor age, race, history of hypertension, history of diabetes, serum creatinine, cerebrovascular cause of death, height, weight, donation after cardiac death, hepatitis C virus status, human leukocyte antigen-B and DR mismatch, cold ischemia time, and double or en bloc transplant. The KDRI reflects the rate of graft failure relative to that of a healthy 40-year-old donor., Results: Transplants of kidneys in the highest KDRI quintile (>1.45) had an adjusted 5-year graft survival of 63%, compared with 82% and 79% in the two lowest KDRI quintiles (<0.79 and 0.79-<0.96, respectively). There is a considerable overlap in the KDRI distribution by expanded and nonexpanded criteria donor classification., Conclusions: The graded impact of KDRI on graft outcome makes it a useful decision-making tool at the time of the deceased donor kidney offer.

Background: Hepatitis C virus (HCV) infection is common among end-stage renal disease patients receiving hemodialysis and a kidney transplant. HCV-positive kidney transplant recipients have worse clinical outcomes than those who are HCV negative. The optimal immunosuppressive regimen in this group of patients remains uncertain., Methods: Using data obtained from the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients, we studied the impact of induction and maintenance immunosuppression on risk of patient death, with death-censored graft failure and death with a functioning graft as secondary endpoints. Cox regression analysis was used to estimate hazard ratios (HR) adjusted for donor, recipient, and transplant variables. A total of 3708 HCV-positive and 75,629 HCV-negative kidney transplant recipients were analyzed., Results: Patient survival was negatively affected by HCV-positive serology. Among HCV-positive kidney transplant recipients, a reduced HR for patient death was observed with the use of induction therapy (HR=0.75, 95% CI 0.61-0.90, P=0.003) and with the use of mycophenolate mofetil (HR=0.77, 95% CI 0.64-0.92, P=0.005)., Conclusions: In kidney transplant recipients with HCV-positive serology, the use of antibody induction did not negatively affect patient survival and the use of mycophenolate mofetil as part of maintenance immunosuppression was associated with better patient survival.

Background: Graft failure related to acute and chronic rejection remains an important problem in transplantation. An association has been reported between microchimerism and the development of tolerance. Since it has been established that cells of fetal origin can be found in maternal tissues long after parturition, and cells of maternal origin may persist for years in offspring, we hypothesized that this fetal-maternal microchimerism may confer tolerance and thus less graft loss for kidneys transplanted between mothers and their offspring., Methods: We used data from the Scientific Registry of Transplant Recipients to compare death-censored graft survival among recipients of living-related renal transplants sharing at least one human leukocyte antigen (HLA) haplotype with their donor. A total of 23,064 such transplants were reported from 1995 to 2004. A Cox proportional hazards model was constructed to compare death-censored graft survival among the following donor-recipient pairings: child-to-mother, child-to-father, mother-to-child, father-to-child, 1-haplotype matched siblings, and HLA-identical siblings., Results: HLA-identical sibling recipients had the best survival, but results for the child-to-father group were not significantly worse (hazard ratio=1.07, P=0.47). Mother-to-child transplants had the poorest graft survival (hazard ratio=2.61, P<0.0001). We found no evidence of tolerance to kidneys transplanted between mothers and offspring., Conclusions: Our analysis of 1-haplotype matched living-related renal transplants argues against tolerance to organs based on fetal-maternal microchimerism. Mechanistic studies examining the relationship between chimerism and immune sensitization would be useful to explore our results, and may contribute to a better understanding of tolerance.

Background: Mortality among patients with chronic liver failure is significantly reduced upon liver transplantation. However, decreases in mortality may not be accompanied by decreases in morbidity metrics, such as hospitalization rates. We compared pre- and posttransplant hospitalization rates for liver transplant recipients., Methods: Statewide hospitalization data were analyzed among 215 adult chronic liver failure patients in Pennsylvania who received a deceased donor transplant from September 2001 to December 2002. Generalized estimating equation (GEE) models were fitted to compare covariate-adjusted pre- and posttransplant hospital admission rates and mean length of stay per admission. The study minimized biases by calculating pre- and posttransplant morbidity in a cohort restricted to patients who received a transplant and were compared to themselves., Results: Liver transplant recipients experienced a significant 70% reduction in hospitalization rates (P<0.0001) posttransplant versus pretransplant. The decline, which occurred for all Model for End-Stage Liver Disease (MELD) subgroups, was significant for patients transplanted at all MELD scores except 6-9. However, even patients with MELD 6-9 experienced a significant decrease in mean length of stay, post versus pretransplant. Higher MELD scores at transplant were generally associated with a greater reduction in hospitalization rates. Also, patients transplanted with lower MELD scores appeared to receive lower quality livers., Conclusions: Our results indicate that the benefit of transplantation extends beyond patient survival and that an important reduction in hospitalization rates is experienced by transplanted patients. Further study is required to determine whether these results are generalizable to the entire United States and to evaluate the donor liver quality used for recipients of different MELD scores.

Background: The magnitude of the survival benefit associated with kidney retransplantation has not been well studied., Methods: Using data from the Canadian Organ Replacement Register (CORR), we studied patients (n=3,067) initiating renal replacement therapy during 1981-1998 who had received a transplant and experienced graft failure (GF). Such patients were followed until death, loss to follow-up or the end of the observation period (December 31, 1998). Using Cox regression, we estimated the post-GF covariate-adjusted hazard ratio (HR) for retransplant versus dialysis, and determined whether the contrast differed across patient subgroups. Through nonproportional hazards models, we also examine patterns in the retransplant/dialysis HR with time following retransplant., Results: Overall, retransplantation is associated with a covariate-adjusted 50% reduction in mortality, relative to remaining on dialysis (HR=0.50; P<0.0001). This benefit is most pronounced in the 18- to 59-year age group. Retransplanted patients were at significantly higher risk of death relative to patients on dialysis only during the first month posttransplant (HR=1.66; P=0.047), and experienced significantly reduced mortality thereafter., Conclusions: Following primary graft failure, retransplantation is associated with significantly reduced mortality rates among Canadian end-stage renal disease patients. Further study should be undertaken to assess the applicability of our findings to other patient populations.