All-cause Graft Failure Research Articles

Highly Sensitized Kidney Transplant Outcomes After the 2014 Kidney Allocation System Change.

Introduction: Kidney Allocation System (KAS) was implemented by United Network for Organ Sharing in 2014 to reduce allocation disparities. Research Questions: Outcomes of highly sensitized patients (calculated panel reactive antibody (cPRA) ≥ 97%) before and after KAS were compared to low-risk recipients (cPRA <10%) in the post-KAS era were examined. The impact on racial disparities was determined. Design: This was a retrospective study of national registry data. Two cohorts of adult candidates waitlisted for deceased donor transplantation during 3-year periods before and after KAS were identified. Results: Highly sensitized patients (N = 1238 and 4687) received a deceased donor kidney transplant between January 1, 2011 and December 31, 2013 and between January 1, 2015 and December, 31, 2017. Racial disparity for highly sensitized patients improved, yet remained significant (P < 0.001), with Black patients comprising 40% and 41% of the highly sensitized candidates and 28% and 34% of the recipients pre- and post-KAS. While posttransplant death-censored graft failure for highly sensitized recipients was similar overall, post-KAS was associated with improved graft survival in the first year after transplant (HR 0.56, 95% CI 0.40-0.78). When compared to contemporaneous lowrisk recipients, both death-censored and all-cause graft failure were similar for highly sensitized recipients and was associated with increased risk for death-censored graft failure beyond the first year (HR 1.39, 95% CI 1.11-1.73). Conclusion: The allocation system led to an increase in transplantation in highly sensitized candidates without compromising outcomes. Although KAS has led to more balanced transplant rates between highly sensitized Black and White patients, racial inequalities persist.

Racial and ethnic disparities in post-liver transplant outcomes for patients with acute-on-chronic liver failure: An analysis of the UNOS database.

The incidence of hospitalisations related to acute-on-chronic liver failure (ACLF) is increasing. Liver transplantation (LT) remains the definitive treatment for the condition. To evaluate the influence of race and ethnicity on LT outcomes in ACLF. We conducted a retrospective analysis utilising LT data from the United Network for Organ Sharing (UNOS) database. White patients served as the control group and patients of other races were compared at each ACLF grade. The primary outcomes assessed were graft failure and all-cause mortality. Blacks exhibited a higher all-cause mortality (Grade 1: aHR 1.36, 95% CI 1.18-1.57, p < 0.001; Grade 2: aHR 1.27, 95% CI 1.08-1.48, p = 0.003; Grade 3: aHR 1.19, 95% CI 1.04-1.37, p = 0.01) and graft failure (Grade 1: aHR 2.05, 95% CI 1.58-2.67, p < 0.001; Grade 2: aHR 1.91, 95% CI 1.43-2.54, p < 0.001; Grade 3: aHR 1.50, 95% CI 1.15-1.96, p = 0.002). Hispanics experienced a lower all-cause mortality at grades 1 and 3 (Grade 1: aHR 0.83, 95% CI 0.72-0.96, p = 0.01; Grade 3: aHR 0.80, 95% CI 0.70-0.91, p < 0.001) and Asians with severe ACLF demonstrated decreased all-cause mortality (Grade 3: aHR 0.55, 95% CI 0.42-0.73, p < 0.001). Black patients experienced the poorest outcomes and Hispanic and Asian patients demonstrated more favourable outcomes compared to Whites.

Predicting outcomes after transplantation of deceased donor kidneys of marginal quality within the Eurotransplant service area.

Kidneys of marginal quality are increasingly being used to overcome the shortage of donor organs. However, accurate prediction of outcome is needed to optimise the use of these kidneys. We aimed to test the performance of a recently proposed score consisting of delayed graft function (DGF), renal function recovery (RFR), and glomerular filtration rate (GFR) &lt;30 ml/min per 1.73 m2 90 days after transplantation for risk assessment of patient and graft survival. A total of 221 adult brain death donors with marginal kidneys, transplanted into 223 recipients within Eurotransplant were included in the analysis. Multivariable Cox proportional hazards models were constructed to assess death-censored and all-cause censored graft failure and recipient mortality at one and three years. Recipients with DGF had a higher risk of death-censored graft loss (HR, 95%CIs: 3.058 (1.195 - 7.825)). Recipients with a GFR &lt;30ml/min/1.73m² at 90 days after transplantation had a higher risk of death censored and all-cause graft failure (HR, 95%CIs: 2.122 (1.129-3.990 and 2.122 (1.129 - 3.990)). None of the three components of the proposed score was associated with a higher risk of mortality. DGF and eGFR &lt;30 ml/min/1.73m² but not RFR at 90 days predicted graft failure after transplantation of marginal kidneys. However, no combination of these factors was able to predict short-term patient and graft survival.

Etiology-Specific Effects of Impaired Functional Status on Liver Transplant Outcomes.

Pre-liver transplant (LT) functional status is an important determinant of prognosis post LT. There is insufficient data on how functional status affects outcomes of transplant recipients based on the specific etiology of liver disease. We stratified LT recipients by etiology of liver disease to evaluate the effects of functional status on post-LT prognosis in each subgroup. 2005-2019 United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) was used to select patients with liver transplant. A total of 14,290 patients were included in the analysis. These patients were stratified by functional status according to Karnofsky Performance Scale (KPS) score: no assistance, some assistance, or total assistance. They were then further divided into six diagnosis categories: metabolic dysfunction-associated steatotic liver disease (MASLD), hereditary disorders, hepatitis C, hepatitis B, autoimmune disease (AID), and alcoholic liver disease (ALD). Primary endpoints included all-cause mortality and graft failure, while secondary endpoints included organ-specific causes of death. Those under the age of 18 and those with non-whole liver or prior liver transplantation were excluded. Patients with MASLD requiring some assistance (aHR: 1.57, 95% CI 1.03-2.39, p = 0.04) and those requiring total assistance (aHR: 2.32, 95% CI 1.48-3.64, p < 0.001) had higher incidences of graft failure compared to those requiring no assistance. Those with MASLD requiring total assistance had a higher all-cause mortality rate than those needing no assistance (aHR: 1.62, 95% CI 1.38-1.89, p < 0.001). Patients with hereditary causes of liver disease showed a lower incidence of all-cause mortality in recipients needing some assistance compared with those needing no assistance (aHR: 0.52, 95% CI 0.34-0.80, p = 0.003). LT recipients with hepatitis C, AID, and ALD all showed higher incidences of all-cause mortality in the total assistance cohort when compared to the no assistance cohort. For the secondary endpoints of specific cause of death, transplant recipients with MASLD needing total assistance had higher rates of death due to general cardiac causes, graft rejection, general infectious causes, sepsis, general renal causes, and general respiratory causes. Patients with MASLD cirrhosis demonstrated the worst overall outcomes, suggesting that this population may be particularly vulnerable. Poor functional status in patients with end-stage liver disease from hepatitis B or hereditary disease was not associated with a significantly increased rate of adverse outcomes, suggesting that the KPS score may not be broadly applicable to all patients awaiting LT.

Long-term follow-up of kidney transplant recipients admitted to a tertiary care transplant center with SARS-CoV-2.

Kidney transplant recipients (KTR) are at risk of severe coronavirus disease 2019 (COVID-19) disease and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We predicted that hospitalization for COVID-19 and subsequent admission to the intensive care unit (ICU) would yield worse outcomes in KTRs. To investigate outcomes among KTRs hospitalized at our high-volume transplant center either on the general hospital floor or the ICU. We retrospectively describe all adult KTRs who were hospitalized at our center with their first SARS-CoV-2 infection between 04/2020 and 04/2022 and had at least 12 months follow-up (unless they experienced graft failure or death). The cohort was stratified by ICU admission. Outcomes of interest included risk factors for ICU admission and mortality, length of stay (LOS), respiratory symptoms at admission, all-cause graft failure at the last follow-up, and death related to COVID-19. 96 KTRs were hospitalized for SARS-COV-2 infection. 21 (22%) required ICU admission. The ICU group had longer hospital LOS (21.8 vs 8.6 days, P < 0.001) and were more likely to experience graft failure (81% vs 31%, P < 0.001). Of those admitted to the ICU, 76% had death at last-follow up, and 71% had death related to COVID-19. Risk factors for ICU admission included male sex (aHR: 3.11, 95%CI: 1.04-9.34; P = 0.04). Risk factors for all-cause mortality and COVID-19-related mortality included ICU admission and advanced age at SARS-CoV-2 diagnosis. Mortality was highest within a month of COVID-19 diagnosis, with the ICU group having increased risk of all-cause (aHR: 11.2, 95%CI: 5.11-24.5; P < 0.001) and COVID-19-related mortality (aHR: 27.2, 95%CI: 8.69-84.9; P < 0.001). ICU admission conferred an increased risk of mortality, graft failure, and longer LOS. One-fifth of those hospitalized died of COVID-19, reflecting the impact of COVID-19-related morbidity and mortality among KTRs.

Kidney Transplant Outcomes From Deceased Donors Who Received Dialysis

Recipient outcomes after kidney transplant from deceased donors who received dialysis prior to kidney donation are not well described. To compare outcomes of transplant recipients who received kidneys from deceased donors who underwent dialysis prior to kidney donation vs recipients of kidneys from deceased donors who did not undergo dialysis. A retrospective cohort study was conducted including data from 58 US organ procurement organizations on deceased kidney donors and kidney transplant recipients. From 2010 to 2018, 805 donors who underwent dialysis prior to kidney donation were identified. The donors who underwent dialysis prior to kidney donation were matched 1:1 with donors who did not undergo dialysis using a rank-based distance matrix algorithm; 1944 kidney transplant recipients were evaluated. Kidney transplants from deceased donors who underwent dialysis prior to kidney donation compared with kidney transplants from deceased donors who did not undergo dialysis. The 4 study outcomes were delayed graft function (defined as receipt of dialysis by the kidney recipient ≤1 week after transplant), all-cause graft failure, death-censored graft failure, and death. From 2010 to 2018, 1.4% of deceased kidney donors (805 of 58 155) underwent dialysis prior to kidney donation. Of these 805 individuals, 523 (65%) donated at least 1 kidney. A total of 969 kidneys (60%) were transplanted and 641 kidneys (40%) were discarded. Among the donors with kidneys transplanted, 514 (mean age, 33 years [SD, 10.8 years]; 98 had hypertension [19.1%] and 36 had diabetes [7%]) underwent dialysis prior to donation and were matched with 514 (mean age, 33 years [SD, 10.9 years]; 98 had hypertension [19.1%] and 36 had diabetes [7%]) who did not undergo dialysis. Kidney transplants from donors who received dialysis prior to donation (n = 954 kidney recipients) were associated with a higher risk of delayed graft function compared with kidney transplants from donors who did not receive dialysis (n = 990 kidney recipients) (59.2% vs 24.6%, respectively; adjusted odds ratio, 4.17 [95% CI, 3.28-5.29]). The incidence rates did not significantly differ at a median follow-up of 34.1 months for all-cause graft failure (43.1 kidney transplants per 1000 person-years from donors who received dialysis prior to donation vs 46.9 kidney transplants per 1000 person-years from donors who did not receive dialysis; adjusted hazard ratio [HR], 0.90 [95% CI, 0.70-1.15]), for death-censored graft failure (22.5 vs 20.6 per 1000 person-years, respectively; adjusted HR, 1.18 [95% CI, 0.83-1.69]), or for death (24.6 vs 30.8 per 1000 person-years; adjusted HR, 0.76 [95% CI, 0.55-1.04]). Compared with receiving a kidney from a deceased donor who did not undergo dialysis, receiving a kidney from a deceased donor who underwent dialysis prior to kidney donation was associated with a significantly higher incidence of delayed graft function, but no significant difference in graft failure or death at follow-up.

Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients.

Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score. This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021. BKV status was classified at 6-months post-transplant as "BKV" or "no BKV" in landmark analysis. Primary outcome was T-cell mediated rejection (TCMR). Secondary outcomes included all-cause graft failure (ACGF), death-censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody-mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups. At 6-months post-transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p=.05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p=.01) and high vs. low-risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p=.02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF. Recipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high-risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.

The impact of macro- and micro-steatosis on the outcomes of patients who undergo liver transplant: Analysis of the UNOS-STAR database.

The presence of steatosis in a donor liver and its relation to post-transplantation outcomes are not well defined. This study evaluates the effect of the presence and severity of micro- and macro-steatosis of a donor graft on post-transplantation outcomes. The UNOS-STAR registry (2005-2019) was used to select patients who received a liver transplant graft with hepatic steatosis. The study cohort was stratified by the presence of macro- or micro-vesicular steatosis, and further stratified by histologic grade of steatosis. The primary endpoints of all-cause mortality and graft failure were compared using sequential Cox regression analysis. Analysis of specific causes of mortality was further performed. There were 9184 with no macro-steatosis (control), 150 with grade 3 macro-steatosis, 822 with grade 2 macro-steatosis and 12 585 with grade 1 macro-steatosis. There were 10 320 without micro-steatosis (control), 478 with grade 3 micro-steatosis, 1539 with grade 2 micro-steatosis and 10 404 with grade 1 micro-steatosis. There was no significant difference in all-cause mortality or graft failure among recipients who received a donor organ with any evidence of macro- or micro-steatosis, compared to those receiving non-steatotic grafts. There was increased mortality due to cardiac arrest among recipients of a grade 2 macro-steatosis donor organ. This study shows no significant difference in all-cause mortality or graft failure among recipients who received a donor liver with any degree of micro- or macro-steatosis. Further analysis identified increased mortality due to specific aetiologies among recipients receiving donor organs with varying grades of macro- and micro-steatosis.

Better kidney allograft survival despite higher-risk donor and recipient characteristics between 1995 and 2014.

Advances in organ procurement, surgical techniques, immunosuppression regimens, and prophylactic antibiotic therapies have dramatically improved kidney transplant graft failure. It is unclear how these interventions have affected longer-term graft failure. It is hypothesized that graft failure has improved over the last 20 years. Data on all first kidney transplants from 1995 to 2014 were extracted from the Australia and New Zealand Dialysis and Transplant Registry with follow-up as of 31 December 2021. Primary exposure was transplant era, classified into 5-year intervals. Primary outcome was all-cause 5-year graft failure. Secondary outcomes included all-cause 10-year graft failure and cause-specific graft failure. Kaplan-Meier curves and multivariable Cox proportional hazards regression models were used to assess trends in all-cause graft failure. Fine-Gray subdistribution hazard models verified that changes in death rates were not biasing the Cox proportional hazards regression models. Cumulative incidence functions were used to assess temporal trends in cause-specific graft failure. Across 10871 kidney transplants, there was a shift towards transplanting more recipients aged >45 years old, with more comorbidities, longer dialysis vintage, body mass index >30kg/m2, and greater human leukocyte antigen mismatches. Donor age has increased but no clear shift in donor source was observed. Compared to 1995-99 (reference), the adjusted hazard ratio for 5-year graft failure was 0.78 (95% CI 0.67-0.91), 0.70 (95% CI 0.59-0.83), and 0.60 (95% CI 0.50-0.73) for 2000-04, 2005-09, and 2010-14, respectively. Ten-year graft failure similarly reduced from 0.83 (95% CI 0.74-0.93) for 2000-04 to 0.78 (95% CI 0.68-0.89) for 2010-14, compared to 1995-99. Medium- and long-term all-cause graft failure has improved steadily since 1995-99. Significant reductions in graft failure due to rejection and vascular causes were observed at 5 years, and due to rejection, vascular causes, death, and glomerular disease at 10 years.

The role of donor sex on the post-liver transplant outcomes in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) can result in hepatic decompensation and require liver transplantation (LT). This study investigates the effect of the sex of the donor and recipient as a prognostic risk factor for adverse outcomes after LT in patients with PSC. UNOS registry was used to select LT patients with PSC from 1987 to 2019. The study cohort was stratified based on the sex of the recipient and further subdivided based on the sex of the donor. The primary endpoints of this study were all-cause mortality and graft failure, which were evaluated using a sequential Cox regression analysis. This study included 2829 patients; 906 female recipients were transplanted from 441 male donors and 465 female donors. 1923 male recipients were transplanted from 1194 male donors and 729 female donors. Within the mismatch analyses, the male-to-male recipients also had a significantly reduced hazard ratio of graft failure compared to female-to-male transplants [aHR 0.51, 95% confidence interval (CI) 0.33-0.79, P = 0.003]. No difference in graft failure was observed in the mismatched female recipient subgroup. The mismatched male recipient group also showed a decreased hazard ratio of mortality from graft rejection and respiratory causes. No differences in specific mortality causes were identified in the mismatched female recipient group. This study demonstrated an increase in the risk of graft failure and mortality secondary to graft failure in male recipients of female donor livers. No differences in mortality or graft failure were identified in female recipients of male livers.

Patient years lost due to cytomegalovirus serostatus mismatching in the scientific registry of transplant recipients.

The cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of overall patient and graft survival. Our primary objective was to describe the short- and long-term risks associated with high-risk CMV donor positive/recipient negative (D+/R-) mismatching among DDKT recipients with the explicit goal of deriving a mathematical mismatching penalty. We conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients (SRTR) database using donor-matched DDKT recipient pairs (N=105,608) transplanted between 2011-2022. All-cause mortality and graft failure hazard ratios were calculated from one year to ten years post-DDKT. All-cause graft failure included death events. Survival curves were calculated using the Kaplan-Meier estimation at 10 years post-DDKT and extrapolated to 20 years to provide the average graft days lost (aGDL) and average patient days lost (aPDL) due to CMV D+/R- serostatus mismatching. We also performed an age-based stratification analysis to compare the relative risk of CMV D+ mismatching by age. Among 31,518 CMV D+/R- recipients, at 1 year post-DDKT, the relative risk of death increased by 29% (p<0.001), and graft failure increased by 17% (p<0.001) as compared to matched CMV D+/R+ group (N=31,518). Age stratification demonstrated a significant increase in the risk associated with CMV mismatching in patients 40 years of age and greater. The aGDL per patient due to mismatching was 125 days and the aPDL per patient was 100 days. The risks of CMV D+/R- mismatching are seen both at 1 year post-DDKT period and accumulated throughout the lifespan of the patient, with the average CMV D+/R- recipient losing more than three months of post-DDKT survival time. CMV D+/R- mismatching poses a more significant risk and a greater health burden than previously reported, thus obviating the need for better preventive strategies including CMV serodirected organ allocation to prolong lifespans and graft survival in high-risk patients.

A2/A2B to B deceased donor kidney transplantation in the Kidney Allocation System era

Kidney transplantation from blood type A2/A2B donors to type B recipients (A2→B) has increased dramatically under the current Kidney Allocation System (KAS). Among living donor transplant recipients, A2-incompatible transplants are associated with an increased risk of all-cause and death-censored graft failure. In light of this, we used data from the Scientific Registry of Transplant Recipients from December 2014 until June 2022 to evaluate the association between A2→B listing and time to deceased donor kidney transplantation (DDKT) and post-DDKT outcomes for A2→B recipients. Among 53 409 type B waitlist registrants, only 12.6% were listed as eligible to accept A2→B offers ("A2-eligible"). The rates of DDKT at 1-, 3-, and 5-years were 32.1%, 61.4%, and 72.1% among A2-eligible candidates and 14.1%, 29.9%, and 44.1% among A2-ineligible candidates, with the former experiencing a 133% higher rate of DDKT (Cox weighted hazard ratio (wHR) = 2.192.332.47; P < .001). The 7-year adjusted mortality was comparable between A2→B and B-ABOc (type B/O donors to B recipients) recipients (wHR 0.780.941.13, P = .5). Moreover, there was no difference between A2→B vs B-ABOc DDKT recipients with regards to death-censored graft failure (wHR 0.771.001.29, P > .9) or all-cause graft loss (wHR 0.820.961.12, P = .6). Following its broader adoption since the implementation of the kidney allocation system, A2→B DDKT appears to be a safe and effective transplant modality for eligible candidates. As such, A2→B listing for eligible type B candidates should be expanded.

Pulmonary artery catheter monitoring versus arterial waveform-based monitoring during liver transplantation: a retrospective cohort study

Although pulmonary artery catheter (PAC) has been used during liver transplantation surgery, the usefulness of PAC has rarely been investigated. We evaluated whether the use of PAC is associated with better clinical outcomes compared to arterial waveform-based monitoring after liver transplantation. A total of 1565 cases undergoing liver transplantation were reviewed. We determined whether patients received PAC or not and divided our cohort into the PAC with hemodynamic monitoring using PAC and the non-PAC with arterial waveform-based monitoring using FloTrac-Vigileo. Propensity score matching was performed. Acute kidney injury (AKI), early allograft dysfunction (EAD) and 1-year all-cause mortality or graft failure were compared in the matched cohorts. Logistic regression analysis was performed in the inverse probability of treatment-weighted (IPTW) cohort for postoperative EAD and AKI, respectively. Five-year overall survival was compared between the two groups. In the matched cohort, there was no significant difference in the incidence of AKI, EAD, length of hospital or ICU stay, and 1-year all-cause mortality between the groups. In the IPTW cohort, the use of PAC was not a significant predictor for AKI or EAD (AKI: odds ratio (95% confidence interval) of 1.20 (0.47–1.56), p = 0.229; EAD: 0.99 (0.38–1.14), p = 0.323). There was no significant difference in the survival between groups after propensity score matching (Log-rank test p = 0.578). In conclusion, posttransplant clinical outcomes were not significantly different between the groups with and without PAC. Anesthetic management without the use of PAC may be possible in low-risk patients during liver transplantation. The risk should be carefully assessed by considering MELD scores, ischemic time, surgical history, previous treatment of underlying liver disease, and degree of portal and pulmonary hypertension.Registration: https://clinicaltrials.gov/ct2/show/NCT05457114 (registration date: July 15, 2022).

Kidney Donation After Circulatory Death Using Thoracoabdominal Normothermic Regional Perfusion: The Largest Report of the United States Experience.

Thoracoabdominal normothermic regional perfusion (TA-NRP) has been increasingly used for donation after circulatory death (DCD) procurements in the United States. We present the largest report of outcomes of kidney transplants performed using DCD donor grafts perfused with TA-NRP. Adult DCD kidney transplants between 2020 and 2022 in the United Network for Organ Sharing database were included. Donors with ≥50 min between asystole and aortic cross-clamp time in which the heart was also transplanted were considered TA-NRP donors. All other donors were considered direct recovery donors. Multivariable regressions were used to assess delayed graft function, as well as posttransplant survival and all-cause graft failure at 30, 90, and 180 d. A propensity-matched analysis of cohorts matched on donor Kidney Donor Profile Index was performed. Of the 16 140 total DCD kidney transplants performed during the study period, 306 (1.9%) used TA-NRP. TA-NRP donors were younger ( P < 0.001) and had lower Kidney Donor Profile Index ( P < 0.001) compared with direct recovery donors. Recipients receiving grafts recovered using TA-NRP were younger ( P < 0.001) and more likely to be blood group O ( P < 0.001). Transplants using TA-NRP had lower likelihood of delayed graft function (adjusted odds ratio 0.22 [95% confidence interval, 0.15-0.31], P < 0.001) but similar 180-d survival ( P = 0.8) and all-cause graft failure ( P = 0.3) as transplants using direct recovery grafts. These inferences were unchanged on propensity-matched analysis. Our results demonstrate that kidney transplants using TA-NRP DCD allografts have positive short-term mortality and graft survival outcomes, with significantly decreased rates of delayed graft function compared with direct recovery DCD grafts.

The impact of recipient and donor gender-match and mismatch on the post-liver transplant outcomes of patients with primary biliary cholangitis.

In this study, we evaluate the effects of donor gender on post-liver transplant (LT) prognosis. We specifically consider patients with primary biliary cholangitis (PBC). The 2005 to 2019 UNOS transplant registry was used to select patients with PBC. The study cohort was stratified by donor gender. All-cause mortality and graft failure hazards were compared using iterative Cox regression analysis. Subanalyses were performed to evaluate gender mismatch on post-LT prognosis. There were 1885 patients with PBC. Of these cases, 965 entries had male donors and 920 had female donors. Median follow-up was 4.82 (25-75% IQR 1.83-8.93) years. Having a male donor was associated with higher all-cause mortality (aHR 1.28 95%CI 1.03-1.58) and graft failure (aHR 1.70 95%CI 1.02-2.82). Corresponding incidence rates were also relatively increased. In the sub-analysis of female recipients (n=1581), those with gender-mismatch (male donors, n=769) were associated with higher all-cause mortality (aHR 1.41 95%CI 1.11-1.78) but not graft failure. In the male recipient subanalysis (n=304), no associations were found between gender-mismatch (female donors, n=108) and all-cause mortality or graft failure. This study shows that recipients who have male donors experienced higher rates of all-cause mortality following LT. This finding was consistent in the female recipient-male donor mismatch cohort.

The Independent Effects of Kidney Length and Vascular Plaque on Ten-Year Outcomes of Extended Criteria Donor Kidney Transplants.

The independent effects of deceased donor kidney length and vascular plaque on long-term graft survival are not established. Utilizing DonorNet attachments from 4,480 expanded criteria donors (ECD) recovered between 2008 and 2012 in the United States with at least one kidney biopsied and transplanted, we analyzed the relationship between kidney length and vascular plaques and 10-year hazard of all-cause graft failure (ACGF) using causal inference methods in a Cox regression framework. The composite plaque score (range 0-4) and the presence of any plaque (yes, no) was also analyzed. Kidney length was modeled both categorically (<10, 10-12, >12cm) as well as numerically, using a restricted cubic spline to capture nonlinearity. Effects of a novel composite plaque score 4 vs. 0 (HR 1.08; 95% CI: 0.96, 1.23) and the presence of any vascular plaque (HR 1.08; 95% CI: 0.98, 1.20) were attenuated after adjustment. Likewise, we identified a potential nonlinear relationship between kidney length and the 10-year hazard of ACGF, however the strength of the relationship was attenuated after adjusting for other donor factors. The independent effects of vascular plaque and kidney length on long-term ECD graft survival were found to be minimal and should not play a significant role in utilization.

Impact of Inflammatory Bowel Disease Subtypes on the Post-liver Transplant Outcomes of Patients with Primary Sclerosing Cholangitis.

Liver transplant patients with primary sclerosing cholangitis often present with concurrent inflammatory bowel disease. The effect of comorbid conditions on post-transplant prognosis was evaluated. The 2005-2019 United Network of Organ Sharing Standard Transplant Analysis and Research database was used to identify patients with primary sclerosing cholangitis. Patients were categorized as having Crohn's Disease, ulcerative colitis, unclassified inflammatory bowel disease, or no inflammatory bowel disease. Baseline characteristics were assessed between cohorts, and outcomes were examined using Cox regression. Outcomes included all-cause mortality, graft failure, infection-induced mortality, and organ system-delineated mortality. Supplementary analyses with unique exclusion and stratification criteria were also performed. Among 2829 patients undergoing transplant, 1360 were considered to have ulcerative colitis, 372 were considered to have Crohn's Disease, and 69 were considered to have an unclassified form of inflammatory bowel disease. Primary sclerosing cholangitis patients with some form of inflammatory bowel disease had no increased risk for any outcomes. However, patients with ulcerative colitis had lower risks of general infectious (aHR 0.65 95%CI 0.44-0.95) and sepsis-induced (aHR 0.56 95%CI 0.35-0.91) mortality, whereas patients with Crohn's Disease had higher risks of sepsis-induced mortality (aHR 2.13 95%CI 1.22-3.70). Supplementary analyses showed effect modification by abdominal surgery history and era. The type of inflammatory bowel disease in liver transplant patients with primary sclerosing cholangitis was found to portend risk difference for infection-induced mortality, with ulcerative colitis found to be protective and Crohn's Disease predictive of increased mortality secondary to infectious etiologies. These associations warrant further investigation.

Donor Diabetes and Steatosis Affects Recipient Survival Following Liver Transplantation Based on Etiology of Liver Cirrhosis.

Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis. Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P < 0.001). Importantly, donor diabetes was associated with increased all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence interval [CI], 1.07-1.19; P < 0.001) and graft failure (HR: 1.16; 95% CI, 1.11-1.22; P < 0.001). Receiving donor organ with diabetes reduced graft survival in patients who received LT for nonalcoholic steatohepatitis cirrhosis (HR: 1.26; 95% CI, 1.13-1.41; P < 0.001) but not other etiologies of cirrhosis. Donor diabetes was associated with worse outcomes post-LT, particularly in patients receiving LT for nonalcoholic steatohepatitis cirrhosis. Future studies are needed to better understand the mechanism underlying this association to develop better risk stratification and clinical practice to improve the outcomes of the transplanted patients.

Sex differences in clinical characteristics and outcomes in patients undergoing heart transplantation.

Whether sex affects selection for and outcomes after heart transplantation (HTx) remains unclear. We aimed to show sex differences in pre-transplant characteristics and outcomes after HTx. From 1995 to 2019, 49200 HTx recipients were prospectively enrolled in the Organ Procurement and Transplantation Network. Logistic regression models were used to evaluate clinical characteristics by sex. Multivariable Cox regression models were fitted to assess sex differences in all-cause mortality, cardiovascular mortality, graft failure, cardiac allograft vasculopathy (CAV), and malignancy. In 49200 patients (median age 55years, interquartile range 46-62; 24.6% women), 49732 events occurred during a median follow-up of 8.1years. Men were older than women, had more often ischaemic cardiomyopathy (odds ratio [OR] 3.26, 95% confidence interval [CI] 3.11-3.42; P<0.001), and a higher burden of cardiovascular risk factors, whereas women had less malignancies (OR 0.47, CI 0.44-0.51; P<0.001). Men were more often treated in intensive care unit (OR 1.24, CI 1.12-1.37; P<0.001) with a higher need for ventilatory (OR 1.24, CI 1.17-1.32; P<0.001) or VAD (OR 1.53, CI 1.45-1.63; P<0.001) support. After multivariable adjustment, men had a higher risk for CAV (hazard ratio [HR] 1.21, CI 1.13-1.29; P<0.001) and malignancy (HR 1.80, CI 1.62-2.00; P<0.001). There were no differences in all-cause mortality, cardiovascular mortality, and graft failure between sexes. In this US transplant registry, men and women differed in pre-transplant characteristics. Male sex was independently associated with incident CAV and malignancy even after multivariable adjustment. Our results underline the need for better personalized post-HTx management and care.

Multiview Clustering to Identify Novel Kidney Donor Phenotypes for Assessing Graft Survival in Older Transplant Recipients.

Older transplant recipients are at a relatively increased risk of graft failure following transplantation and some of this risk may relate to donor characteristics. Unsupervised clustering using machine learning may be a novel approach to identify donor phenotypes that may then be used to evaluate outcomes for older recipients. Using a cohort of older recipients, the purpose of this study was to A) use unsupervised clustering to identify donor phenotypes and B) determine the risk of death/graft failure for recipients of each donor phenotype. We analyzed a nationally representative cohort of kidney transplant recipients age >65 years captured using the Scientific Registry of Transplant Recipients between 2000-2017. Unsupervised clustering was used to generate phenotypes using donor characteristics inclusive of variables in the kidney donor risk index (KDRI). Cluster assignment was internally validated. Outcomes included all-cause graft failure (including mortality) and delayed graft function (DGF). Differences in the distribution of KDRI scores were also compared across the clusters. All-cause graft failure was compared for recipients of donor kidneys from each cluster using a multivariable Cox-Survival analysis. Overall, 23,558 donors were separated into five clusters. The area under the curve for internal validation of cluster assignment was 0.89. Recipients of donor kidneys from two clusters were found to be at high risk of all-cause graft failure relative to the lowest risk cluster (adjusted hazards ratio 1.86, 95% CI 1.69-2.05 and 1.73, 95% CI 1.61-1.87). Only, one of these high-risk clusters had high proportions of donors with established risk factors (i.e., hypertension, diabetes). KDRI scores were similar for the highest and lowest risk clusters (1.40 [1.18-1.67] and 1.37 [1.15-1.65], respectively). Unsupervised clustering can identify novel donor phenotypes comprised of established donor characteristics that, in turn, may be associated with different risks of graft loss for older transplant recipients.