Worse Graft Research Articles

Recurrence of autoimmune liver diseases after liver transplantation: Review and expert opinion statement.

Autoimmune liver diseases (AILDs) constitute the fourth most common indication for liver transplantation (LT) across the world. In general, the outcomes after LT are acceptable; however, disease recurrence after LT is common for all AILD, which can negatively affect graft and overall survival. Several questions persist, including the risk factors associated with recurrent disease, optimal antirejection medications, strategies to reduce the risk of recurrence, and how to best incorporate these strategies into clinical practice. For that reason, we assembled an international group of experts to review evidence to address these outstanding questions regarding LT for AILD. Survival rates after LT are ~90% and 70% at 1 and 5 years, and recurrent disease occurs in 10%-50% of patients with AILD. In patients with disease recurrence, graft survival decreased by 18% and 28% and overall survival by 8% and 12% at 5 and 10 years after LT, respectively. Recurrent autoimmune hepatitis is associated with high aminotransferases and immunoglobulin G (IgG) before LT, lymphoplasmacytic infiltrates in the explants, and may be associated with the absence of steroids after LT. However, the efficiency and safety of triple immunosuppressive maintenance therapy is still debatable. Younger age at diagnosis with primary biliary cholangitis or LT is associated with primary biliary cholangitis recurrence. Preventive use of ursodeoxycholic acid reduces the risk of recurrence and has a benefit in graft and patient survival. Episodes of systemic inflammation, including T-cell-mediated rejection, active ulcerative colitis, and episodes of cholangitis, are associated with recurrent PSC. Recurrent disease for AILD is associated with worse graft and patient survival. Patients with autoimmune hepatitis could be considered for long-term low-dose predniso(lo)ne, whereas patients with primary biliary cholangitis should be placed on preventive ursodeoxycholic acid after LT. There are no specific treatments for PSC recurrence; however, adequate control of inflammatory bowel disease and optimal immunosuppression to avoid T-cell-mediated rejection should be encouraged.

Disparities in Liver Transplantation for Nonalcoholic Steatohepatitis in Women.

Nonalcoholic steatohepatitis (NASH) is the fastest-growing indication for liver transplantation (LT). Sex disparities among patients with cirrhosis on the LT waitlist are well known. We wanted to understand these disparities further in women with end-stage liver disease patients listed for NASH cirrhosis in a contemporary cohort. We used data from the Scientific Registry of Transplant Recipients to assess sex racial, and ethnic differences in NASH patients listed for LT. Adults transplanted from August 1997 to June 2021 were included. Inferential statistics were used to evaluate differences with univariate and multivariate comparisons, including competitive risk analysis. During the study time period, we evaluated 12 844 LT for NASH cirrhosis. Women were transplanted at a lower rate (46.5% versus 53.5%; P < 0.001) and higher model for end-stage liver disease (MELD) (23.8 versus 22.6; P < 0.001) than men. Non-White women were transplanted at a higher MELD (26.1 versus 23.1; P < 0.001) than White women and non-White male patients (26.1 versus 24.8; P < 0.001). Graft and patient survivals were significantly different ( P < 0.001) between non-White women and White women and men (White and non-White). Evaluation of LT candidates in the United States demonstrates women with NASH cirrhosis have a higher MELD than men at LT. Additional disparities exist among non-White women with NASH as they have higher MELD and creatinine at LT compared with White women. After LT, non-White women have worse graft and patient survival compared with men or White women. These data indicate that non-White women with NASH are the most vulnerable on the LT waitlist.

The impact of colonic allograft inclusion on intestinal transplantation outcomes: Results from UNOS/OPTN database analysis.

Outcomes of intestinal transplantation with colon allograft (ICTx) remain controversial. We aimed to assess the outcomes of ICTx in comparison to intestinal transplantation without colon (ITx) using the UNOS/OPTN registry database. We retrospectively reviewed 2612 patients who received primary intestinal transplants from 1998 to 2020. The rates of acute rejection (AR) within 6 months after transplant were compared between ICTx and ITx. Risk factors of 6-month AR were examined using logistic regression model by era. Furthermore, conditional graft survival was analyzed to determine long-term outcomes of ICTx. Of 2612 recipients, 506 (19.4%) received ICTx. Graft and patient survival in ICTx recipients were comparable to those in ITx recipients. White ICTx recipients had a higher incidence of AR within 6 months compared to ITx during the entire study period (p=.002), colonic inclusion did not increase the risk of 6-month AR in the past decade. ICTx recipients who experienced 6-month AR had worse graft and patient survival compared to those who did not (p<.001 and p=.004, respectively). Among patients who did not develop 6-month AR, Cox proportional hazard model analysis revealed that colonic inclusion was independently associated with improved conditional graft survival. In the recent transplant era, colonic inclusion is no longer associated with a heightened risk of 6-month AR and may provide better long-term survival compared to ITx when AR is absent. Risk adjustment for rejection and proper immunosuppressive therapy are crucial to maximize the benefits of colonic inclusion.

Taking a Big Breath: Identifying and Preventing Pulmonary Complications After Liver Transplantation.

In this issue of Transplantation, Oh et al1 describe the results of a retrospective study of postoperative pulmonary complications (PPCs) in 608 patients who underwent living donor liver transplantation over a period of 9 y. More than half of the patients developed pulmonary complications defined as respiratory failure, pneumonia, pulmonary edema, moderate-severe atelectasis, or pleural effusions within 7 d after the transplant. The authors found that a large number of intraoperative variables were associated with PPC including (not surprisingly) Model for End-stage Liver Disease score, ventilator driving pressures, positive end-expiratory pressure (PEEP) and compliance, fluid and blood administration, and duration of anesthesia. However, when using a multivariate analysis and focusing on intraoperative factors, greater driving pressure, and albumin levels at the end of surgery, prolonged hypotension and larger tidal volumes (but not PEEP) remained independently associated with PPC. Patient with PPCs had worse outcomes such as longer intensive care unit stay and worse graft and patient survival. This is the first, larger study of PPC after liver transplantation that investigates the effect of intraoperative variables and therefore factors that may be modifiable. Although any retrospective study can only identify associations and not prove causal relationships, this study provides us with evidence that may influence how we manage patients. Specifically, the association of driving pressures at the end of surgery confirms what we have learned from the nontransplant anesthesiology literature: intraoperative ventilator management matters. Almost 10 y ago, Futier et al2 demonstrated the benefit of intraoperative lung-protective ventilation including the use of PEEP to prevent PPC after abdominal surgery with the landmark randomized, controlled Intraoperative Protective Ventilation trial. The benefit of using PEEP shown in the Intraoperative Protective Ventilation trial could not be replicated in the present study. This may reflect more recent evidence that suggests that high driving pressure (and tidal volumes) and not just low PEEP are actually harmful,3 and PEEP should be individualized to the patient’s static compliance. The ongoing Prime-Air study (ClinicalTrials.gov Identifier: NCT04108130) is a large, multicenter, randomized, controlled trial of an anesthetic-center bundle of interventions that includes individualized PEEP. This study will likely provide us with a better understanding if and how individualized PEEP may be beneficial. Other factors identified by this study associated with PPCs such as low albumin levels at the end of surgery and intraoperative hypotension require more complex physiologic explanations and are not as easily modifiable. PPCs are usually defined as any serious respiratory complications after surgery independent of their etiology.4 Cardiogenic pulmonary edema, pneumonias, and pleural effusions are all considered PPCs, although they represent very different pathologies. PPC is a syndrome with often vague and subjective definitions. For example, the severity of atelectasis or pleural effusion is difficult to quantify and what some may consider normal postoperative changes may be considered PPC by others. The elegant solution to this problem by the present study was to assess for PPCs with radiograph and chart review by 2 pulmonologists. Although this method allows for the application of some common sense in the diagnosis of PPC, it is harder to quantify severity. For example, is severe atelectasis equally harmful than pneumonia? Unlike other organ injuries such as acute kidney injury or liver failure, there are no proven sensitive and specific biomarkers that allow us to identify PPCs and assess its severity. This should not discourage us as it is a great opportunity for future research that may dramatically transform clinical studies of PPCs and possible interventions. The present study is further encouraging as it demonstrates that interventions in the operating room affect complications and the anesthesiologist as an integral member of transplant team can contribute to better outcomes for our patients.

A Comparative Study on Graft and Overall Survival Rates Between Diabetic and Nondiabetic Kidney Transplant Patients Through Survival Analysis.

Patients with diabetes mellitus (DM) have worse graft and overall survival, but recent evidence suggests that the difference is no longer significant. To compare the outcomes between patients with end-stage kidney disease due to DM (ESKD-DM) and ESKD due to nondiabetic etiology (ESKD-non-DM) who underwent kidney transplantation (KT) up to 10 years of follow-up. Survival analysis of a retrospective cohort. All patients who underwent KT at the Hospital Universitario San Ignacio, Colombia, between 2004 and 2022. Overall and graft survival in ESKD-DM and ESKD-non-DM who received KT. Patients who died with functional graft were censored for the calculation of kidney graft survival. Log-rank test, Cox proportional hazards model, and competing risk analysis were used to compare overall and graft survival in patients with ESKD-DM and ESKD-non-DM who underwent KT. A total of 375 patients were included: 60 (16%) with ESKD-DM and 315 (84%) with ESKD-non-DM. Median follow-up was 83.3 months. Overall survival was lower in patients with ESKD-DM at 5 (75.0% vs 90.8%, P < .001) and 10 years (55.0% vs 86.7%, P < .001). Cardiovascular death was higher in patients with diabetes (27.3% vs 8.2%, P = .021). Death-censored graft survival was similar in both groups (96.7% vs 93.3% at 5 years, P = .324). On multivariate analysis, the factors associated with global survival were DM (hazard ratio [HR] = 2.11, 95% confidence interval [CI] = 1.23-3.60, P = .006), recipient age (HR = 1.05, 95% CI = 1.02-1.08, P < .001), delayed graft function (HR = 2.07, 95% CI = 1.24-3.46, P = .005), and donor age (HR = 1.03, 95% CI = 1.01-1.05, P = .002). In the competing risk analysis, DM was associated with mortality only in the cardiovascular death group (sub-hazard ratio [SHR] = 6.06, 95% CI = 1.01-36.4, P = .049). Change in diabetes treatment received over time and adherence to glycemic targets were not considered. The sample size is relatively small, which limits the precision of our estimates. The Kidney Donor Profile Index and the occurrence of treated acute rejection were not included in the regression models. Overall survival is lower in patients with diabetes, possibly due to older age and cardiovascular comorbidities. Therefore, patients with diabetes should be followed more closely to control cardiovascular risk factors. However, there is no difference in graft survival.

P15.05: Safety of Once-Weekly Dulaglutide on Post-transplant Diabetes Mellitus: A Preliminary Single-Centre Experience

Introduction: Almost all immunosuppressive drugs (IS), including glucocorticoids, calcineurin and mTOR inhibitors, play a central role in the development of Post-Transplant Diabetes Mellitus (PTDM). IS potentially cause the development of a dysglycemic state, both for the direct cytotoxic action on pancreatic beta cells and for the induction of insulin resistance. PTDM is also associated with increased risk for cardiovascular disease and with worse graft and patients’ survival. Currently there are no clear recommendations on the choice of the most safe and effective anti-diabetic drug for PTDM. IS are linked with several pharmacokinetic interactions and burdened with vary degree of nephrotoxicity. Glucagon like peptide- 1 receptor agonists (GLP1RA) are largely used for the treatment of type 2 diabetes. They act stimulating endogenous insulin secretion in a glucose-dependent manner. GLP1RAs reduce blood sugar by stimulating insulin release, suppressing high glucagon levels, delaying gastric emptying, and reducing food intake. Furthermore, GLP1 has been shown to promote proliferation of beta cells in animal models. GLP1RA has proven to be safe and effective in reducing HbA1c without directly causing hypoglycemia and has shown a clear association with cardiovascular risk reduction and renal protection. Despite GLP1RA seems to act with a mechanism that perfectly contrasts the pathogenetic aspects of PTDM, in the literature clinical experience is entirely limited to case series and retrospective studies. Method: In order to assess primarily safety of GLP1RA therapy in patients with PTDM we have prospectively enrolled a sample of N = 20 patients referred to liver (N = 10), renal (N = 5), as well as heart (N = 4) and lung (N = 1) transplant at ISMETT. All patients were placed on once-weekly dulaglutide therapy. Weight, HbA1c Level, as well as complete lipid profile and liver function tests were performed at 3 months and again at 6 months. One-way Repeated measurements ANOVA was used to test significant change in collected variables over time. Results: The study was closed at 6 months follow-up visit. Mild gastrointestinal symptoms were experienced by patients at the treatment start and resolved in 2 weeks. There were no persistent side effects due to dulaglutide in our study population and all recruited patients were on dulaglutide at 6 months evaluation. Body weight, Total cholesterol, Fibrosis-4 Index, alanine aminotransferase and aspartate aminotransferase levels were all reduced at the end of the follow-up, while blood glucose as well as HbA1c were stable over time (Table 1, Figure 1). Conclusion: Dulaglutide has proven to be safe in a population of transplanted patients with PTDM. In addition, a significative reduction of metabolic parameters was found. GLP1RA could be a preferred treatment for patients with PTDM considering also the extraglycemic effects of cardiovascular and renal protection.

Decline in Functional Status While on the Waiting List Predicts Worse Survival After Lung Transplantation

To determine if decreases in the Karnofsky Performance Score (KPS) while on the waitlist predict decreased survival after lung transplantation (LTx). A retrospective evaluation of the United Network for Organ Sharing database. The KPS was evaluated at the time of listing for transplant and at the time of transplantation. Group I consisted of patients having a decrease in KPS during the time on the waiting list (from the time of listing to the time of transplant), and Group II consisted of patients whose KPS stayed the same or increased during the same period. The authors used propensity-score weighting for comparisons of these groups. Retrospective observational database review. Adult patients undergoing lung transplantation. None. Patients were stratified according to a change in their KPS. Patient and graft survival of patients with decreasing or not decreasing KPS were compared. Of the 27,558 subjects included in the analysis, 17,986 (65%) had worsening KPS, which was associated with worse graft (p=0.0003) and patient (p=0.0019) survival after LTx. Using multivariate regression, a decrease in KPS of ≥40 was associated with decreased survival, and an increase of ≥40 was associated with improved survival (HR=1.245, 95% CI [1.181-1.312], p < 0.0001 and HR=0.866, 95% CI [0.785, 0.955], respectively). Among patients with a KPS <40 at the time of transplant, those with a decrease in KPS of ≥40 had decreased graft and patient survival compared with those with a smaller decrease (p=0.0002 and p=0.0021, respectively). Deterioration of KPS on the waiting list for LTx is associated with significantly greater postoperative mortality in patients after LTx. These results should be taken into consideration when allocating organs. Strategies to increase or to prevent a decrease in KPS before LTx should be evaluated.

Outcomes after Liver Transplantation with Steatotic Grafts: Redefining Acceptable Cutoffs for Steatotic Grafts.

Graft macrosteatosis can predispose to a higher risk of graft loss so we sought to redefine acceptable cutoffs for graft steatosis. Data of 26,103 donors who underwent liver transplantation (LT) between January 2004 and December 2018 from the UNOS-STAR database were utilized. A high-risk steatotic (HRS) graft and a low-risk steatotic (LRS) graft were defined as ≥20% and <20% macrosteatosis, respectively. High-risk steatotic grafts were further classified as grafts with 20-29% (G1S grafts), 30-39% (G2S grafts), and ≥40% steatosis (G3S grafts). Outcomes between groups were compared. LRS grafts had excellent graft (93.3 and 87.7%) and overall survival (95.4 and 90.5%) at 90 days and 1 year. Compared to LRS grafts, G1S, G2S, and G3S grafts had worse graft and overall survival at 90 days and 1-year (p <0.001). There was no difference in graft or overall survival of G1S or G3S grafts compared to G2S grafts until after adjustment in which G3S grafts were found to be associated with an increased risk of graft loss-aHR 1.27 (1.03-1.57), p = 0.02. Liver grafts can be categorized into three categories: (1) <20% or "very low risk", (2) 20-39% or "low-to-moderate risk", and usually acceptable, and (3) ≥40% steatosis or "moderate-to-high risk". Da BL, Satiya J, Heda RP, et al. Outcomes after Liver Transplantation with Steatotic Grafts: Redefining Acceptable Cutoffs for Steatotic Grafts. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S5-S14.

MO998: Kidney Donor Risk Index Correlates with the Worse Recipients And Grafts Survival in a Polish Cohort

Abstract BACKGROUND AND AIMS Kidney transplant outcomes are the result of a combination of different factors, including donor factors, that influence graft allocation. Kidney Donor Risk Index (KDRI) quantifies the donor risk and is used to predict the outcome of a kidney transplantation from a deceased donor in the US. However, its value in the European populations has not yet been well established. The aim of this retrospective study was to evaluate the correlation between KDRI and recipient cardiovascular events as well as kidney graft and overall survival in a Polish cohort. METHOD We conducted a retrospective single-center cohort study of 813 adult patients who received deceased donor kidney transplant (KTx) at the Hospital of Medical University of Silesia, Katowice, Poland between January 2010 and December 2017 and were followed until December 2021. Living donor recipients as well as multiple organs transplantations were excluded. KDRI was calculated according to formula proposed by Rao and patients were divided into quartiles of KDRI values. Kidney graft function was analyzed using the estimated glomerular filtration rate (eGFR) using MDRD formula at 3, 6 and 12 months after KTx and every 12 months thereafter. Cardiovascular (CVE) events such as cardiac death, stroke, myocardial infarction, and acute coronary syndrome were monitored throughout the study period. The correlation between KDRI and eGFR was calculated using the Pearson test. Kaplan–Meier survival method and Mantel-Cox analysis were performed in order to analyze the impact of the KDRI categories on graft loss, death censored graft survival and patient outcomes (CVE and death from any cause). RESULTS There was no statistical difference in the pretransplant dialysis vintage, duration of pretransplant hypertension, residual diuresis or history of cardio-vascular events between the patients receiving kidneys from different KDRI quartile groups. Patients in Q1 group were significantly younger (47.3 ± 12.8 versus 54.5 ± 12.7 years, P &amp;lt; 0.001) and have a shorter cold ischemia time (16.8 ± 6.5 versus 19.5 ± 6.4 h, P&amp;lt; 0.01) compared with the Q4 KDRI patients. The mean eGFR was significantly higher in the highest KDRI quartile compared with the lowest one throughout the study (66 ± 21 versus 43 ± 16 mL/min, P &amp;lt; 0.001 at month 3; 68 ± 21 versus 44 ± 1 5 mL/min, P &amp;lt; 0.001 at month 12; 66 ± 20 versus 43 ± 14 mL/min, P &amp;lt; 0.001 at month 48, respectively). A significant negative correlation was found between KDRI and eGFR throughout (r = −0.43, P &amp;lt; 0.001 at month 3 to r = −0.45, P &amp;lt; 0.001 at month 48, ). There was a statistically significant difference in death censored kidney graft survival (P = 0.01) among the four KDRI quartile groups displayed with the Kaplan–Meier curves in Figure 1. There was a significant difference in CVE-free survival (P &amp;lt; 0.001) between the quartiles (displayed on the Kaplan–Meier curve in Figure 2). CONCLUSION 1. In patients after kidney transplantation KDRI correlates with the worse graft and patients outcomes. 2. KDRI may be an adequate and valuable prognostic tool for Polish population of kidney graft recipients.

MO979: Influence of BK Virus Plasma Viral Load in Kidney Transplant Outcomes

Abstract BACKGROUND AND AIMS BK virus infection (BKi) is an important cause of kidney transplant (KT) loss. Besides to reducing immunosuppression, the rest of the therapies have not shown a clear benefit. Our purpose is to analyze the risk factors for BKi and the influence of BK plasma viral load on KT outcomes. METHOD Prospective cohort study of KT with BKi, defined by the presence of BK viremia in ≥3 consecutive determinations, from 01 January 2010 to 31 December 2020. BK viremia was determined every 10 days during the first 3 months, at 6th month, 12th month and in case of impaired renal function. In patients with positive viremia, immunosuppressive therapy was changed (reduction/discontinuation of mycophenolate and/or switching to everolimus). Patients with high-level viremia (≥10 000 copies/mL) and low-level viremia (&amp;lt;10 000 copies/mL) were compared. To identify risk factors for BKi, for each KT with BKi, we selected two matched controls and performed a logistic regression analysis. Graft survival was analyzed according to BK viremia (high-level, low-level and negative) using Kaplan–Meier and Cox regression analysis was performed to determine risk factors for graft survival. RESULTS 849 KT were performed, of which 67 (7.9%) presented BKi. Six KT were excluded due to incomplete data. Finally, 61 KT BKi (n = 27, high-level viremia; n = 34 low-level viremia) and 122 controls were analyzed. The median post-KT time to BKi was 2 months. In the multivariable analysis, male recipient, older age and re-KT were risk factors for BKi. Proven BK-associated nephropathy was diagnosed in five KT recipients and nine patients had persistent BK viremia, all of them from the high plasma viral loads group. Only one patient lost the graft due to BK-associated nephropathy. Patients with low-level viremia had worse renal function one month after KT than controls but without differences at the first year. Patients with high-level viremia had worse renal function one year after KT and worse graft survival than recipients with low-level viremia and controls (P = 0.037). In the multivariable analysis, when we analyzed exclusively patients with BKi, high-level viremia was a risk factor for kidney graft survival (HR: 16.31; P = 0.034). CONCLUSION BKi is not an uncommon complication after KT. Only high BK viral load was associated with BK-associated nephropathy, persistent viremia, and poorer graft survival. BK viremia &amp;lt;10 000 copies/mL did not affect KT outcomes. Therefore, monitoring BK plasma viral loads and changes in immunosuppression to reduce viremia are effective strategies to minimize the impact of BK virus on graft survival.

FC 108: Gene Expression Profiles of Peritubular Capillaritis in Chronic Antibody-Mediated Rejection

Abstract BACKGROUND AND AIMS Chronic antibody-mediated rejection (ABMR) is one of the most significant contributors to late allograft loss. Hallmark characteristics of ABMR include microvascular injury (MVI) lesions such as peritubular capillaritis (ptc) and glomerulitis (g). Diffuse ptc (extent &amp;gt; 50%) was associated with worse graft survival independent from the ptc score. Nevertheless, current ptc thresholds are arbitrarily defined and may not reflect pathophysiological phenotypes accurately enough. The Banff peritubular capillaritis working group has been re-established to study the diagnostic and prognostic relevance of the ptc extent in different scenarios. We hypothesize that the re-assessment of chronic ABMR specimens using Nanostring NCounter based gene expression analysis allows the definition of novel thresholds of ptc extent, reflecting molecular ABMR phenotypes more accurately. METHOD We retrospectively analysed 25 patients with historical diagnosis of ABMR/chronic ABMR and presence of donor specific antibodies (including 44 biopsies). Patients were treated at two different Austrian centres (Medical University of Vienna and Ordensklinikum—Elisabethinnen Linz). Peritubular capillaritis was re-evaluated by an experienced external nephropathologist (M.M.) and included the ptc score as well as the ptc extent (focal ptc: 10–50% capillaries involved, diffuse ptc: &amp;gt;50%). Nanostring nCounter Gene expression analysis was performed with a customized gene set corresponding to the recommendations of molecular ABMR phenotypes in Banff 2017 guidelines (including over 200 genes). To test the correlation of gene expression levels and histological scores, gene expression levels of all 44 patients were divided into quartiles. Gene expressions above the first quartile (ABMRQ&amp;gt;1) were considered as positive values for ROC analysis. RESULTS Ptc was categorized as followed: no ptc in 13, focal ptc in 23 and diffuse ptc in seven biopsies [median ptc extent 25/0–40% (median/IQR)]. ABMR was diagnosed in 27 (67.5%) biopsies, mixed rejection in five (12.5%) and borderline TCMR in three (7.5%). In biopsies with diffuse ptc significant higher gene expressions were found in the ABMR gene set [63/55–83 versus 32/27–52; (median/IQR); P = 0.012], the ABMR exhaust gene set (390/245–609 versus 245/128–358; P = 0.022), the Eculizumab gene set (180/143–339 versus 65/57–133; P = 0.0027) and the TCMR gene set (48/40–75 versus 25/19–35; P = 0.001). Sensitivity analysis revealed improved AUCs for predicting biopsies with ABMR gene expressions over the first quartile with a ptc cutoff of 35% compared to ptc cut-off of 50% [ptc&amp;gt;35: AUC 0.76/0.61–0.90 (95% confidence interval); P = 0.013; ptc&amp;gt;50: AUC: 0.71/0.54–0.88; P = 0.039]. The new ptc&amp;gt;35% cutoff also provided higher AUCs for the prediction of gene expressions over the 25th percentile in all other analysed rejection-associated gene sets. CONCLUSION With the application of gene expression-based Nanostring platform, we were able to identify a new threshold of ptc extent. The newly proposed cut off &amp;gt;35% may reflect molecular phenotypes of ABMR more accurate than the current one and could improve early diagnosis of ABMR.

512 Systemic Norepinephrine Impact on Tangential Split Thickness Skin Graft Outcomes in Burn Shock Patients

IntroductionBlood pressure supporting agents like vasopressors are often used to treat patients with burn shock. Norepinephrine is part of the algorithms used by regional burn centers for fluid resuscitation in burn shock. In our population of burn shock patients, we have noticed an association of poor graft take when norepinephrine is used. We undertook this study to assess the relationship between systemic norepinephrine use and split-thickness skin graft (STSG) healing.MethodsWe retrospectively identified burn patients who presented to our burn center from January 2014 –June 2020, who were treated with systemic vasopressors within the first 48 hours of admission, and received at least one tangential excision and STSG procedure as part of their treatment. We compared these patients to a matched control group of burn patients who did not receive vasopressors for resuscitative purposes. The primary outcome investigated was graft take percentage at time of graft takedown.ResultsDuring the time frame, we found 19 patients and 19 matched controls within the same time period who did not receive norepinephrine. The mean percent graft take for patients treated with systemic norepinephrine was 77.9% (SE = 3.00), which was significantly lower than that of the control group, 92.8% (SE = 3.56) (P= < 0.001). Furthermore, patients who received norepinephrine had a statistically significant increase in both hospital (P= 0.038) and intensive care unit (ICU) length of stay (P= 0.009). The two populations were equivalent in all other characteristics such as TBSA, number of comorbidities, age, and resuscitation volumes.ConclusionsIn this retrospective assessment, the use of norepinephrine seems to have a significant association with worse graft take and longer length of stay. Since graft loss begets more graft reoperations and a longer stay, our findings would lead one to incorporate norepinephrine as a last resort in the treatment algorithm for burn shock.

Remnant lipoprotein cholesterol is associated with incident new onset diabetes after transplantation (NODAT) in renal transplant recipients: results of the TransplantLines Biobank and cohort Studies

BackgroundNew onset diabetes after transplantation (NODAT) is a frequent and serious complication of renal transplantation resulting in worse graft and patient outcomes. The pathophysiology of NODAT is incompletely understood, and no prospective biomarkers have been established to predict NODAT risk in renal transplant recipients (RTR). The present work aimed to determine whether remnant lipoprotein (RLP) cholesterol could serve as such a biomarker that would also provide a novel target for therapeutic intervention.MethodsThis longitudinal cohort study included 480 RTR free of diabetes at baseline. 53 patients (11%) were diagnosed with NODAT during a median [interquartile range, IQR] follow-up of 5.2 [4.1–5.8] years. RLP cholesterol was calculated by subtracting HDL and LDL cholesterol from total cholesterol values (all directly measured).ResultsBaseline remnant cholesterol values were significantly higher in RTR who subsequently developed NODAT (0.9 [0.5–1.2] mmol/L vs. 0.6 [0.4–0.9] mmol/L, p = 0.001). Kaplan-Meier analysis showed that higher RLP cholesterol values were associated with an increased risk of incident NODAT (log rank test, p < 0.001). Cox regression demonstrated a significant longitudinal association between baseline RLP cholesterol levels and NODAT (HR, 2.27 [1.64–3.14] per 1 SD increase, p < 0.001) that remained after adjusting for plasma glucose and HbA1c (p = 0.002), HDL and LDL cholesterol (p = 0.008) and use of immunosuppressive medication (p < 0.001), among others. Adding baseline remnant cholesterol to the Framingham Diabetes Risk Score significantly improved NODAT prediction (change in C-statistic, p = 0.01).ConclusionsThis study demonstrates that baseline RLP cholesterol levels strongly associate with incident NODAT independent of several other recognized risk factors.

Association Between Cytomegalovirus Serostatus, Antiviral Therapy, and Allograft Survival in Pediatric Heart Transplantation.

Background: Cytomegalovirus (CMV) is an important complication of heart transplantation and has been associated with graft loss in adults. The data in pediatric transplantation, however, is limited and conflicting. We conducted a large-scale cohort study to better characterize the relationship between CMV serostatus, CMV antiviral use, and graft survival in pediatric heart transplantation. Methods: 4,968 pediatric recipients of solitary heart transplants from the Scientific Registry of Transplant Recipients were stratified into three groups based on donor or recipient seropositivity and antiviral use: CMV seronegative (CMV-) transplants, CMV seropositive (CMV+) transplants without antiviral therapy, and CMV+ transplants with antiviral therapy. The primary endpoint was retransplantation or death. Results: CMV+ transplants without antiviral therapy experienced worse graft survival than CMV+ transplants with antiviral therapy (10-year: 57 vs 65%). CMV+ transplants with antiviral therapy experienced similar survival as CMV- transplants. Compared to CMV seronegativity, CMV seropositivity without antiviral therapy had a hazard ratio of 1.21 (1.07–1.37 95% CI, p-value = .003). Amongst CMV+ transplants, antiviral therapy had a hazard ratio of .82 (0.74–.92 95% CI, p-value < .001). During the first year after transplantation, these hazard ratios were 1.32 (1.06–1.64 95% CI, p-value .014) and .59 (.48–.73 95% CI, p-value < .001), respectively. Conclusions: CMV seropositivity is associated with an increased risk of graft loss in pediatric heart transplant recipients, which occurs early after transplantation and may be mitigated by antiviral therapy.

Trends of kidney transplantation from the 2020 annual report on kidney disease in Taiwan

Renal transplantation (RTX) is the treatment of choice for end-stage kidney disease (ESKD). Taiwan has the highest incidence and prevalence of ESKD in this world. This is the first study to illustrate the national registry database of RTX. All patients who received RTX in Taiwan between 2010 and 2018 were enrolled in this study. Demographic data and comorbidities were obtained from the National Health Insurance Research Database and Transplantation Society of Taiwan. Graft and patient survival rates were also analyzed. Men were more likely to receive RTX. During the observation periods, > 30% of the recipients were relatively young (20-44 years). The percentage of preemptive RTX (p=0.014) and living RTX (p=0.022) increased annually with statistical significance (linear regression model). Recently, recipients had more cardiovascular disease (p=0.014), diabetes mellitus (p=0.097), and hypertension (p=0.021). The mean duration of graft survival increased yearly (p=0.001). The proportion of patients surviving till age of ≧65 years increased significantly with time (2.2% in 2010, 33.1% in 2018) (p<0.0001). Younger recipients (<44 years) had significantly better survival than the elderly (≧65 years). Patients with diabetes were more likely to have worse graft and patient survival rates. Recipients enrolled in pre-ESRD care program had better graft and patient survival rates than those not enrolled in these care program. The proportion of preemptive and livingdonor RTX increased but was still low. Despite increased number of commodities in recipients, graft and patient survival have increased recently. Enrolling patients with CKD in pre-ESRD care program was associated with better graft and patient survival.

Early Allograft Dysfunction Is Associated with Higher Complication Rate after Liver Transplantation

Introduction: Liver transplantation is considered as the standard of care for patients with end-stage liver diseases. However, an early graft dysfunction (EAD) is still one of the many challenges that clinicians have to overcome. EAD has a varying incidence between 10.8% to 36.3% and the association between EAD and worse graft or patient survival rate has been repeatedly reported; however, little has been conducted about the postoperative complications after occurrence of EAD which lead subsequently to higher mortality among EAD patients. Method: We performed a retrospective analysis on patients who underwent liver transplantation from January 2007 to July 2012. For definition of EAD we adopted the Olthoff criteria. All complications were classified in accordance to the time-dependent occurrence as “early”, “intermediate” or “late”. Results: From a total of 555 patients, 214 (38.6%) developed EAD. Both 12 month graft and patient survival rate were significantly worse in EAD patients. Analysis of complications rate showed that EAD patients had higher rate of sepsis (p=0.001), acute renal failure (p<0.001) and bleeding postoperatively (p=0.012). EAD development was associated with higher likelihood for reoperation and retransplantation (p=0.04 and p<0.001). Within first week after transplantation, EAD patients had higher rate of sepsis and postoperative bleeding (p<0.001, p=0.015); however incidences of intermediate and late complications did not differ. Conclusions: Patients who develop EAD have significantly higher rate of early sepsis, postoperative bleeding and acute kidney injury, which constitute worse outcomes. Patients with EAD are more likely to have a reoperation and/or retransplantation.

God is a Female Plant: Femininity and Divinity in the Stories of Anne Richter, Kathe Koja, and Karen Russell

ABSTRACT This essay is concerned with the relationship between femininity and divinity in feminist speculative fiction. It equates becoming divine with becoming plant, and studies the transformations that attend women in this process in modernity, postmodernity and transmodernity. Taking as its point of departure Mark Taylor’s evolution of the concept of God through immanence, transcendence and immanent transcendence, and Rosa María Rodríguez Magda’s definition of transmodernity, it examines “The Sleep of Plants” (1967) by Anne Richter, “The Neglected Garden” (1991) by Kathe Koja, and “The Bad Graft” (2014) by Karen Russell. It argues that by becoming plants these women locate themselves in opposition to the norms of divinity created by men, and proposes to delineate the contours of a new feminist paradigm in the present transmodern age through the study of botany.

Age and sex determine conversion from immediate-release to extended-release tacrolimus in a multi-center cohort of Canadian pediatric renal transplant recipients.

ER-Tac, taken once per day, is associated with improved adherence. This study examined the potential patient and clinical factors that influence clinicians to convert pediatric patients from immediate-release to ER-Tac. This prospective multi-center observational study followed Canadian pediatric kidney transplant recipients up to 5years post-transplant. Cox Proportional Hazards Regression was used to examine the influence of factors on conversion to ER-Tac. Sixty-six participants were included in this analysis. For every additional year of age at the time of transplant, the likelihood of conversion was more than doubled (HR 2.54, CI 1.83, 3.54, P<0.001). The impact of age reduced by three percent for every month after transplant (HR 0.97, CI 0.95, 0.98, P<0.001). Girls were more likely to be converted than boys (HR 3.78, CI 1.35, 10.6, P 0.01). Adherence measures (MAM-MM and tacrolimus trough variability), individual barriers to adherence, renal function, HLA mismatch, and rejection were not significant predictors of conversion in the final regression model. ER-Tac was preferentially prescribed to older age and female patients. Female sex and adolescence are both associated with worse graft outcomes, but we found no link between individualized markers of adherence/graft risk and conversion. Clinicians appeared to be using demographic features to distinguish patients at perceived higher risk and converted accordingly, without a case-by-case evaluation of who is more susceptible to poor outcomes.

P1657GRAFT- AND PATIENT-SURVIVAL IN TRANSPLANT KIDNEY PATIENTS UNDERGOING TRANSPLANT BIOPSIES

Abstract Background and Aims Kidney transplantation is a frequent treatment in uremic patients. However, long term patency is limited. The aim of this study was to investigate the histological findings in transplant biopsies in relation to clinical outcome in patients. Method 1542 patients (36.4 % women) were included if they had a first kidney transplant registered in a quality assessment registry (period October 24, 1968 and August 28, 2017) and also had registered a first transplant kidney biopsy during the period January 1, 2007 until Mars 2, 2018. Graft- and patient-survival analysis was performed by Kaplan-Meier- and Cox-regression-analysis (adjusted for age and gender). Data are presented as Hazard Ratio (HR) and 95% Confidence Intervals (CI). A two-sided p-value of &amp;lt;0.05 was considered as statistically significant. Results Patients with primary and recurrent glomerulonephritis (GN) found in the biopsy had a worse graft- (70% at 5-year) and patient-survival (85% at 5-year) compared to all other diagnoses (p&amp;lt;0.05). Comparing with GN as reference group with respect to graft-loss the risk was lower if biopsies revealed infections (HR 0.3, CI 0.1-0.9), chronic damages (HR 0.38, CI 0.2-0.6), CNI-toxicity (HR 0.3, CI 0.2-0.6) or rejection (HR 0.5, CI 0.3-0.9). Looking at patient-survival, compared to those with GN a lower risk for early death was found for those with tubulointerstitial diseases (HR 0.35, CI 0.1-0.9), chronic damages (HR 0.35, CI 0.2-0.7), CNI-toxicity (HR 0.4, CI 0.2-0.9) and rejection (HR 0.4, CI 0.2-0.9) while those with hematological diseases (HR 14, CI 3.7-53.6) had higher risk for early death. Comparing subgroups within rejections, there was a significant (p&amp;lt;0.01) better graft-survival in patients with cellular rejection or borderline changes (90% at 5-year) versus those with humoral (65% at 5-year), chronic humoral and cellular rejection (60% at 5-year), and transplant-glomerulopathy (TGP) (70% at 5-year). The patient-survival was worse for patients with a TGP (70% at 5-year) compared to cellular rejections (p=0.04). Patients with humoral (HR 4.4, CI 2.3-8.4), chronic humoral and cellular rejection (HR 5.8, CI 2.9-9.9) and TGP (HR 3.7, CI 1.6-8.8) had higher risk for graft-loss and patients with TGP (HR 3.5, CI 1.2-10.5) had higher risk for early death compared to cellular rejection as reference. In addition, it was found that the median time between the graft-loss and death (25 patients) was 76 days (mean 304 days) and 44% of these patients died within 30 days after graft-loss. The median age of these patients was 62 years. Between the patients who died within 30 days and the others, no differences were found in cause of death, findings in the transplant kidney biopsies or type of transplant kidney (living versus deceased). Conclusion Patients with GN and patients with TGP had a worse outcome in both graft- and patient-survival. Awareness should focus on the patients who die soon after graft-loss.

P1667ANALYSIS OF RISK FACTORS FOR CMV DISEASE IN KIDNEY TRANSPLANT PATIENTS - SINGLE CENTER STUDY

Abstract Background and Aims Cytomegalovirus (CMV) disease and infection negatively influence outcome of kidney transplantation. The aim of this retrospective study was to analyze risk factors for CMV disease and its influence on kidney graft function and survival. Method 1050 patients underwent kidney transplantation from January 2014 to December 2018 and received calcineurin inhibitor, mycophenolate mofetil and steroid-based immunosuppression. Recipients with PRA&amp;gt;20% received rATG while others had received basiliximab as induction. 825 out of 1050 patients (78.6%) received CMV prophylaxis (D+/R-, n=173; R+, n=652). Patients were followed up to 71 months /median 38 months/. Results CMV tissue invasive disease occurred in 49 out of 1050 patients (4.7%), while CMV infection in 87 patients (8.3%). CMV disease, but not CMV infection, had significant negative influence on graft survival at 5 years post transplantation (p=0.0029). Patients with CMV disease had significantly worse graft function at 4 years post transplantation (p&amp;lt;0.0001). CMV disease occurred in 31 out of 173 patients (17.9%) in D+/R- group vs. 18 out of 652 patients (2.8%) in R+ group. Incidence of CMV infection was 30/173 patients (17.3%) in D+/R- group vs. 57/652 patients (8.7%) with induction therapy. Shortening of CMV prophylaxis was found in 82 patients (9.9%). Leukopenia (≤ 2.0 x 109/L) was observed in 97 (11.7%) patients from those who received CMV prophylaxis, Its shortening significantly increased risk for both CMV infection (20,7% vs. 7.2%, p&amp;lt;0,0001) and CMV disease (8,5% vs. 4,2%, p=0,04). Among most significant risk factors for CMV disease in univariable analysis were CMV mismatch (OR 11, 95% CI: 5,9-20,4; p&amp;lt;0,0001), delayed graft function (OR 2,8, 95% CI: 1,6-5,1; p&amp;lt;0,0001, cadaveric donor (OR 6, 95% CI: 1,5-25,1; p=0,00013) and shortening of CMV prophylaxis (OR 2.1, 95% CI: 0,91-4,86; p=0,08). Multivariable analysis revealed as independent significant predictors of CMV disease DGF (OR 2,29, 95% CI: 1,2-4,3; p=0,01) and CMV mismatch (OR 10,8, 95% CI: 5,7-20,6; p&amp;lt;0.0001) in a model adjusted for type of donor, prophylaxis shortening and leukopenia. Conclusion CMV mismatch is the main independent predictor of CMV disease after kidney transplantation in multivariable analysis.