One-year Graft Loss Research Articles

Short-Term and Long-Term Effects of Ischemic Conditioning on Liver Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Although liver transplantation (LT) is one of the definitive treatments for patients with end-stage liver failure, it inevitably results in ischemic reperfusion injury. It is known that prognosis is improved when temporary ischemic conditioning (IC) is applied to patients with ischemic reperfusion injury. The objective of this meta-analysis was to determine the short-term and long-term effects of IC on the clinical outcomes of LT recipients. Randomized controlled studies on IC in patients with LTs were included. Patients were compared between an IC group and a sham group. Studies were retrieved from PubMed, Embase, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. Mortality, graft function, and major complications were synthesized using RevMan 5.4.1. Among 316 papers, 17 articles (1196 patients) were included. There was an insignificant increase in short-term mortality (risk ratio [RR]: 3.00, 95% CI: 0.32-28.14, P=.34). However, long-term mortality was lower in the IC group than in the sham group, but not significantly (RR: 0.75; 95% CI: 0.47-1.20, P=.23). Short-term graft function (acute graft rejection and primary graft non-function) was not improved by IC. One-year graft loss tended to show better results in the IC group (RR: 0.53, 95% CI: 0.26-1.07, P=.08). Ischemic conditioning did not have a beneficial effect on LT. Although long-term outcomes appear to be better in the IC group than in the sham group, further randomized controlled trials are needed.

Liver Transplant Recipient Characteristics Associated With Worse Post-Transplant Outcomes in Using Elderly Donors

Advanced age of liver donor is a risk factor for graft loss after transplant. We sought to identify recipient characteristics associated with negative post-liver transplant (LT) outcomes in the context of elderly donors. Using 2014–2019 OPTN/UNOS data, LT recipients were classified by donor age: ≥70, 40–69, and <40 years. Recipient risk factors for one-year graft loss were identified and created a risk stratification system and validated it using 2020 OPTN/UNOS data set. At transplant, significant recipient risk factors for one-year graft loss were: previous liver transplant (adjusted hazard ratio [aHR] 4.37, 95%CI 1.98–9.65); mechanical ventilation (aHR 4.28, 95%CI 1.95–9.43); portal thrombus (aHR 1.87, 95%CI 1.26–2.77); serum sodium <125 mEq/L (aHR 2.88, 95%CI 1.34–6.20); and Karnofsky score 10–30% (aHR 2.03, 95%CI 1.13–3.65), 40–60% (aHR 1.65, 95%CI 1.08–2.51). Using those risk factors and multiplying HRs, recipients were divided into low-risk (n = 931) and high-risk (n = 294). Adjusted risk of one-year graft loss in the low-risk recipient group was similar to that of patients with younger donors; results were consistent using validation dataset. Our results show that a system of careful recipient selection can reduce the risks of graft loss associated with older donor age.

Association between Kasai portoenterostomy at low caseload centres and transplant complications in children with biliary atresia

BackgroundKasai portoenterostomy (KPE) is the preferred treatment for biliary atresia (BA) patients. It has been shown that the center caseload of KPE impacts on native liver survival. We aimed to define the impact of KPE caseload on complications at the time of liver transplantation (LT). MethodsRetrospective data collection of LT for BA performed in our tertiary center between 2010 and 2018. The patients were grouped according to the caseload of the center that performed KPE: Group A (≥5 KPE/year) and Group B (<5 KPE/year). We analyzed total transplant time (TTT), hepatectomy time, amount of plasma and red blood cell (RBC) transfusions, occurrence of bowel perforations at LT. ResultsAmong 115 patients, Group A (n 44) and Group B (n 71) were comparable for age, sex, PELD score, TTT. The groups differed for: median hepatectomy time (57 min, IQR = 50–67; vs 65, IQR 55–89, p = 0.045); RBC transfusions (95 ml, IQR 0–250; vs 200 ml, IQR 70–500, p = 0.017); bowel perforations (0/44 vs 15/71, p = 0.001). One-year graft loss in Group A vs Group B was 1/44 vs 7/71 (p = 0.239), whereas deaths were 0/44 vs 5/71 respectively (p = 0.183); 5/15 patients who had a perforation eventually lost the graft. ConclusionsThis study found an association between KPE performed in low caseload center and the incidence of complications at LT. These patients tend to have a worse outcome. The centralization of KPE to referral center represents an advantage at the time of LT. Mini abstractWe studied the impact of Kasai portoenterostomy (KPE) caseload on complications at the time of liver transplantation (LT), in 115 patients. We found an association between KPE performed in low caseload center and increased bowel perforations and blood transfusions. We suggest to centralize to experienced center all children requiring KPE.

Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies

Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions to improve predictive utility and constructed a deep-learning-based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte infiltrates. Periodic acid- Schiff stained slides of transplant biopsies (60 training and 33 testing) were used to quantify pathological lesions specific for interstitium, tubules and mononuclear leukocyte infiltration. The pipeline was applied to the whole slide images from 789 transplant biopsies (478 baseline [pre-implantation] and 311 post-transplant 12-month protocol biopsies) in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss. Our model accurately recognized kidney tissue compartments and mononuclear leukocytes. The digital features significantly correlated with revised Banff 2007 scores but were more sensitive to subtle pathological changes below the thresholds in the Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of one-year graft loss, while a Composite Damage Score in 12-month post-transplant protocol biopsies predicted later graft loss. ITASs and Composite Damage Scores outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITASs or Composite Damage Scores also demonstrated significantly higher incidence of estimated glomerular filtration rate decline and subsequent graft damage. Thus, our deep-learning approach accurately detected and quantified pathological lesions from baseline or post-transplant biopsies and demonstrated superior ability for prediction of post-transplant graft loss with potential application as a prevention, risk stratification or monitoring tool.

Transplantation of kidneys after normothermic perfusion: A single center experience.

In order to expand the pool of usable donors from circulatory death (DCD) there is increasing interest in normothermic regional perfusion (NRP) to assess and improve liver viability.1,2 NRP may also improve outcomes in kidney transplantation.We present our single center experience of outcomes in imported kidneys following NRP. Data was obtained from a prospectively maintained database between December 2012 and September 2018. Primary endpoints were incidence of delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). Six-hundred and thirty-two decease donor kidneys were transplanted, 229 from DCD donors, 29 of which had NRP. The DGF rate was lower for NRP versus DCD (six of 29, 20.7% vs. 70 of 200, 35.0%) with reduced duration of DGF. Multivariate analysis demonstrated transplant type to be a statistically significant independent predictor of eGFR at 7 and 14 days. Early transplant function in NRP kidneys was comparable to DBD. There were no graft losses within 30 days in the NRP group. One-year graft loss rate was 3.4% for NRP and 6.0% for standard DCD. This data suggests NRP is safe, and reduces rates of DGF and improves early renal transplant function.

BARRIERS IN ACCESS TO LIVER TRANSPLANTATION FOR ETHNIC MINORITY CHILDREN IN THE UNITED STATES DO NOT TRANSLATE INTO INFERIOR OUTCOMES

Purpose: Disparities in children undergoing liver transplantation (LT) exist and have been attributed to a combination of racial and socioeconomic circumstances. We sought to evaluate the influence of those barriers in access to LT on graft and patient survival. Methodology: We evaluated data from the U.S. Scientific Registry of Transplant Recipients (SRTR) of all pediatric (<18 years old) LT recipients from 1999 to 2014 and compared outcomes by race or ethnicity: Hispanic, non-Hispanic White (NHW), and non-Hispanic Blacks (NHB). We assessed 1- and 5-year patient survival (PS) and death-censored graft survival (DCGS). Characteristics controlled for included: living or deceased donor, brain- or cardiac-death donor (DCD), graft type (whole, partial, split), recipient age, BMI, primary disease, PELD score, re-transplant status, graft rejection, functional status, and cold ischemia time (CIT). Cox regression analysis was used with an alpha level of 0.05. Results: During the 15-year period, 8,331 (4,876 NHW, 1,522 NHB, and 1,933 Hispanic) pediatric LT procedures were performed in the U.S. Hispanic children were listed and transplanted at a significantly younger age (4.4, 4.8, respectively) than NHW (5.2, 5.6; p<0.001) and NHB children (5.1, 5.5; p<0.001). Compared to NHW (15.3%) and NHB (20.3%), there was a greater proportion of Hispanic children requiring total functional assistance (23.7%; p<0.001) at LT. Additionally, NHB and Hispanic children had exception points approved with lower frequency than NHW (p=0.036). Compared to NHW (14.2%), NHB (7.5%) and Hispanic (11.5%) children were less likely to have a living donor (p<0.001). NHB were more likely to receive a whole deceased donor graft (69.4%) than NHW or Hispanic children (63.4% and 59.6%, respectively; p<0.001). However, Hispanic children were more likely to receive a split deceased donor graft (19.8% for Hispanics, 12.9% for NHW, 14.7% for NHB; p<0.001). Listing PELD was higher for Hispanics (21.1±11.3) and NHB (20.4±10.7), compared to NHW (20.0±10.8; p=0.023). One-year PS for NHW, NHB, and Hispanics was 82.9%, 83.2%, and 83.1%, respectively; one-year DCGS was 82.8%, 83.1%, and 83.0%, respectively. Five-year PS for NHW, NHB, and Hispanics was 60.6%, 58.5%, and 57.9%, respectively; five-year DCGS was 60.6%, 58.5%, and 57.9%, respectively. None of these was significantly different in any two-way comparison.Multivariate analysis of one-year graft loss showed that older recipient age (HR 0.962, 95% CI 0.943-0.982) was protective while re-transplant status (1.554, 1.180-2.048) and the need for functional assistance (3.079, 2.307-4.109) were predictive of graft loss. Conclusion: Barriers exist for minority children to navigate the LT listing process. However, once transplanted, Hispanic and NHB children outcomes are comparable to NHW. Further research is necessary to understand and ease barriers in accessing LT for minority children.

Peri‐transplant lactate levels and delayed lactate clearance as predictive factors for poor outcomes after liver transplantation: A propensity score–matched study

This study aimed to investigate risk factors for early allograft dysfunction (EAD) and outcomes after liver transplantation (LT), focusing on peri-transplant lactate clearance. We reviewed patients who underwent deceased donor LTs between 2011 and 2014. Lactate levels were checked at reperfusion and at the time of intensive care unit admission. Early lactate clearance was defined as reduction rate of lactate between the times of reperfusion and immediately after LT. Patients were categorized into the normal and delayed clearance groups. We used propensity score matching (PSM) between these two groups to estimate an impact of lactate clearance on incidence of EAD and graft survival. A total of 256 recipients were eligible for this study. Cut-off value of lactate clearance to predict occurrence of EAD was determined at 0.2mmol/L/h. After PSM, 120 patients in the normal clearance and 36 patients in the delayed clearance group were matched. Delayed lactate clearance was considered as an independent risk factor for EAD (Odds ratio 3.49, P=0.002). The adjusted hazard of one-year graft loss was significantly increased in the delayed clearance group (hazard ratio 6.69, P=0.001). In conclusion, peri-transplant delayed lactate clearance may be a strong predictor for EAD and poor liver graft outcomes.

Dual kidney transplantation as a strategy to use expanded criteria donors: a systematic review

The objective of this review was to assess whether dual kidney transplantation (DKT) is better than single KT (SKT) for optimizing the use of expanded criteria donor kidneys. We did a systematic literature search and meta-analyses when possible, pooling data for calculating relative risks (RR) of major outcomes. Twenty-five studies met the inclusion criteria. One-year serum creatinine was better after DKT vs. SKT (mean difference -0.27 [-0.37, -0.17], P<0.001), with less incidence of acute rejection (RR 0.66 [0.52, 0.85], P<0.001) and without differences at five years. Less DGF was seen in DKT (RR 0.88 [0.76, 1.02], P=0.09). Mortality at 1 and 3years was similar after dual or SKT, but mortality at five years was lower after DKT (RR 0.71 [0.53, 0.94], P=0.02). One-year graft loss was similar between dual (n=4158) and SKT (n=51800) (RR 0.97 [0.87, 1.09], P=0.62). Three- and five-year graft loss was not considered because of high heterogeneity between studies. In conclusion, short-term graft function and long-term patient survival are better in recipients receiving DKT vs. SKT. However, these differences are based on few retrospective reports with a relatively low number of cases. Good quality randomized controlled trials are needed to assess whether the investment of two kidneys in one recipient is justified in face of the current organ shortage.

Effect of early allograft dysfunction on outcomes following liver transplantation.

Early allograft dysfunction (EAD) following liver transplantation (LT) remains a challenge for patients and clinicians. We retrospectively analyzed the effect of pre-defined EAD on outcomes in a 10-year cohort of deceased-donor LT recipients with clearly defined exclusion criteria. EAD was defined by at least one of the following: AST or ALT >2000IU/L within first-week post-LT, total bilirubin ≥10mg/dL, and/or INR ≥1.6 on post-operative day 7. Ten patients developed primary graft failure and were analyzed separately. EAD occurred in 86 (36%) recipients in a final cohort of 239 patients. In univariate and multivariate analyses, EAD was significantly associated with mechanical ventilation ≥2days or death on days 0, 1, PACU/SICU stay >2days or death on days 0-2 and renal failure (RF) at time of hospital discharge (all P<.05). EAD was also significantly associated with higher one-year graft loss in both uni- and multivariate Cox hazard analyses (P=.0203 and .0248, respectively). There was no difference in patient mortality between groups in either of the Cox proportional hazard models. In conclusion, we observed significant effects of EAD on short-term post-LT outcomes and lower graft survival.

Big Data, Predictive Analytics, and Quality Improvement in Kidney Transplantation: A Proof of Concept.

We sought proof of concept of a Big Data Solution incorporating longitudinal structured and unstructured patient-level data from electronic health records (EHR) to predict graft loss (GL) and mortality. For a quality improvement initiative, GL and mortality prediction models were constructed using baseline and follow-up data (0-90 days posttransplant; structured and unstructured for 1-year models; data up to 1 year for 3-year models) on adult solitary kidney transplant recipients transplanted during 2007-2015 as follows: Model 1: United Network for Organ Sharing (UNOS) data; Model 2: UNOS & Transplant Database (Tx Database) data; Model 3: UNOS, Tx Database & EHR comorbidity data; and Model 4: UNOS, Tx Database, EHR data, Posttransplant trajectory data, and unstructured data. A 10% 3-year GL rate was observed among 891 patients (2007-2015). Layering of data sources improved model performance; Model 1: area under the curve (AUC), 0.66; (95% confidence interval [CI]: 0.60, 0.72); Model 2: AUC, 0.68; (95% CI: 0.61-0.74); Model 3: AUC, 0.72; (95% CI: 0.66-077); Model 4: AUC, 0.84, (95 % CI: 0.79-0.89). One-year GL (AUC, 0.87; Model 4) and 3-year mortality (AUC, 0.84; Model 4) models performed similarly. A Big Data approach significantly adds efficacy to GL and mortality prediction models and is EHR deployable to optimize outcomes.

REGISTRY REPORT ON PANCREAS RETRANSPLANTATION: LOWER INCIDENCE OF REJECTION IN THE TACROLIMUS ERA

688 Introduction: Between 10/01/87 and 11/30/97, 5742 cadaver pancreas (Pa) transplants (Txs) with complete information on immunosuppression therapy were reported to the International Pa Tx Registry (IPTR) and the United Network for Organ Sharing (UNOS). Of these, 3.8% were Pa reTxs. Outcome of Pa reTxs has not been studied in detail since the introduction of tacrolimus (as a substitute for cyclosporine) and mycophenolate mofetil (as a substitute for azathioprine). Patients. Of 209 Pa reTxs, 115 (56%) were rePa after kidney Txs[rePAK], 47 (22%) were rePaTxs alone [rePTA], and 47 (22%) re-simultaneous Pa-kidney Tx [reSPK]. RePAK accounted for 25% of all PAK, reSPK for only 1% of all SPK. Mainstay immunosuppressants were cyclosporine (1987-93) and, more recently, tacrolimus (94-97). Results. Pa graft survival for both primary and reTxs has significantly improved over time. One year graft survival rates for rePAK increased from 59% (1987-89) to 67% (1994-97); for rePTA, from 50% to 71%; for reSPK, from 50% to 84% (Table). The rate of technical failures of reTxs compared with primary Txs was not different for rePAK, but was higher for rePTA and reSPK. According to a univariate analysis, graft loss from rejection decreased significantly over time. One-year graft loss from rejection for rePAK decreased from 34% to 8%; for rePTA, from 39% to 20%; for reSPK, from 12% to 5%. According to a multivariate analysis, the most important risk factor for patient survival after reTxs was recipient age (risk of death increased by a factor of 3 for each 20-year increment). The most important risk factors for graft survival after reTxs were recipient and donor age (10-year increments) and poor HLA matching (particularly for rePAK and rePTA).Conclusions: 1. Graft survival for rePAK, rePTA, and reSPK improved significantly with the use of tacrolimus; in reSPK, with the use of MMF. 2. Graft loss from rejection was significantly higher in enteric versus bladder drained rePAK and rePTA (but not reSPK). 3. Good HLA matching(≥3 antigens) for rePAK and rePTA and the use of tacrolimus for rePAK, rePTA, and reSPK significantly decreased the risk of graft loss from rejection.

REGISTRY REPORT ON PANCREAS RETRANSPLANTATION: LOWER INCIDENCE OF REJECTION IN THE TACROLIMUS ERA.

688 Introduction: Between 10/01/87 and 11/30/97, 5742 cadaver pancreas (Pa) transplants (Txs) with complete information on immunosuppression therapy were reported to the International Pa Tx Registry (IPTR) and the United Network for Organ Sharing (UNOS). Of these, 3.8% were Pa reTxs. Outcome of Pa reTxs has not been studied in detail since the introduction of tacrolimus (as a substitute for cyclosporine) and mycophenolate mofetil (as a substitute for azathioprine). Patients. Of 209 Pa reTxs, 115 (56%) were rePa after kidney Txs[rePAK], 47 (22%) were rePaTxs alone [rePTA], and 47 (22%) re-simultaneous Pa-kidney Tx [reSPK]. RePAK accounted for 25% of all PAK, reSPK for only 1% of all SPK. Mainstay immunosuppressants were cyclosporine (1987-93) and, more recently, tacrolimus (94-97). Results. Pa graft survival for both primary and reTxs has significantly improved over time. One year graft survival rates for rePAK increased from 59% (1987-89) to 67% (1994-97); for rePTA, from 50% to 71%; for reSPK, from 50% to 84% (Table).The rate of technical failures of reTxs compared with primary Txs was not different for rePAK, but was higher for rePTA and reSPK. According to a univariate analysis, graft loss from rejection decreased significantly over time. One-year graft loss from rejection for rePAK decreased from 34% to 8%; for rePTA, from 39% to 20%; for reSPK, from 12% to 5%. According to a multivariate analysis, the most important risk factor for patient survival after reTxs was recipient age (risk of death increased by a factor of 3 for each 20-year increment). The most important risk factors for graft survival after reTxs were recipient and donor age (10-year increments) and poor HLA matching (particularly for rePAK and rePTA). Conclusions: 1. Graft survival for rePAK, rePTA, and reSPK improved significantly with the use of tacrolimus; in reSPK, with the use of MMF. 2. Graft loss from rejection was significantly higher in enteric versus bladder drained rePAK and rePTA (but not reSPK). 3. Good HLA matching (≥3 antigens) for rePAK and rePTA and the use of tacrolimus for rePAK, rePTA, and reSPK significantly decreased the risk of graft loss from rejection.