Selection Of Patients For Transplantation Research Articles

Key challenges of post-liver transplant weight management

Liver transplantation serves as a life-saving intervention for patients with end-stage liver disease, yet long-term survival remains a challenge. Post-liver transplant obesity seems to have a significant contribution to this challenge and it emerges as a significant risk factor for graft steatosis, metabolic syndrome and de-novo malignancy development. This review synthesizes current literature on prevalence, risk factors and management strategies for post-liver transplant obesity, emphasizing its impact on graft and patient survival. Literature review consultation was conducted in Medline/PubMed, SciELO and EMBASE, with the combination of the following keywords: Weight management, liver transplantation, immunosuppressive therapy, lifestyle interventions, bariatric surgery. Immunosuppressive therapy has a significant influence on long-term survival of liver transplant patients, yet it seems to have lesser effect on post-transplant obesity development than previously thought. However, it significantly contributes to the development of other components of metabolic syndrome. Key predisposing factors for post-transplant obesity development encompass elevated recipient and donor body mass index, a history of alcoholic liver disease, hepatocellular carcinoma, male gender, the absence of cellular rejection and the marital status of the recipient. Tailored immunosuppressive regimens, pharmacotherapy, lifestyle interventions and bariatric surgery represent key components in mitigating post-transplant obesity and improving long-term survival and quality of life in this group of patients. Timely identification and intervention thus hold paramount importance. Further research is warranted to refine optimal management strategies and enhance outcomes in this patient population.

Evolution of Pancreas Transplantation At A Single Institution-50+ Years and 2500 Transplants.

To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past 5 decades. The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care. A single-center retrospective review of 2500 pancreas transplants was performed over >50 years in bivariate and multivariable models. Transplants were divided into 6 eras; outcomes are presented for the entire cohort and by era. All measures of patient and graft survival improved progressively through the 6 transplant eras. The overall death-censored pancreas graft half-lives were >35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year death-censored pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall, graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time. Pancreas outcomes have significantly improved over time through sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss.

245.3: Sirolimus treatment increases graft survival in pediatric intestinal transplant patients and is associated with a more naïve/less activated immune phenotype, and a higher frequency of regulatry T-cells.

245.3: Sirolimus treatment increases graft survival in pediatric intestinal transplant patients and is associated with a more naïve/less activated immune phenotype, and a higher frequency of regulatry T-cells.

Risk factors and prognostic modeling in bridging extracorporeal membrane oxygenation patients before lung transplantation.

The increased use of preoperative extracorporeal membrane oxygenation (ECMO) as a life support system before lung transplantation demands a better understanding of the associated prognostic factors. This study aims to discern the critical factors influencing the survival outcomes of ECMO patients and design a prognostic model tailored to this patient group. We retrospectively gathered and analyzed baseline and clinical data of patients who underwent preoperative bridging ECMO before lung transplantation from the United Network for Organ Sharing (UNOS) database. Univariate and multivariate Cox regression analyses were conducted and a prognostic model was generated to identify the independent factors influencing survival outcomes in these patients. The predictive model was cross-validated using the k-fold method where k=5. Our study included 1,202 patients. Both single and multiple analyses showed that age over 51 years, high body mass index (BMI), a history of dialysis before transplantation, donor hypertension, prolonged cold ischemia time, and high serum total bilirubin are adverse prognostic factors for the survival of ECMO-bridged lung transplant patients. Using the multivariate analysis, we created a prognosis model and a nomogram to predict 1-year post-transplant survival, with a receiver operating characteristic (ROC) curve area of 0.760 in internal validation. The 1-year survival rate calibration curve supported the nomogram's accuracy. This study involved the development of a survival prognosis model for patients undergoing lung transplantation with preoperative ECMO bridging, which was validated through extensive data analysis. The prognosis model exhibited high accuracy and predictive capability, effectively predicting the survival outcomes of patients both pre- and post-surgery.

Impact of Renin-Angiotensin System Blockade on Mortality and Allograft Loss among Renal Transplant Recipients: A Systematic Review and Meta-Analysis.

The blockade of the renin-angiotensin system (RAS) has a beneficial effect on reducing the levels of proteinuria and blood pressure in patients with chronic kidney disease (CKD) and reduces the risk of developing end-stage kidney disease in CKD patients. Nonetheless, a debate persists regarding the impact of RAS inhibitors on outcomes such as mortality and graft survival in renal transplant patients. To assess the effect of RAS inhibitors on graft recipients in the past decade, we conducted a systematic review and meta-analysis. We searched Embase, PubMed, and the Cochrane Central Register of Clinical Trials from January 1, 2012, to August 1, 2022. We included 14 articles, comprising 5 randomized controlled trials (RCTs) and 9 cohort studies, including 45,377 patients. These studies compared patient or graft survival between an RAS inhibitor treatment arm and a control arm. The meta-analysis revealed that RAS blockade was significantly associated with lower mortality in cohort studies (risk ratio [RR] = 0.66, 95% confidence interval [CI]: 0.55-0.79), reduced allograft loss in cohort studies (RR = 0.62, 95% CI: 0.54-0.71), and significant changes in systolic blood pressure in RCTs. Subgroup analysis of the groups of interest (interventions involving RAS blockade, follow-up period of ≥5 years) showed consistently reduced mortality (RR = 0.67, 95% CI: 0.56-0.81) and reduced allograft loss (RR = 0.61, 95% CI: 0.54-0.70). Our results demonstrated that the application of RAS blockade among renal transplant recipients was associated with lower mortality and allograft loss in cohort studies but not in RCTs. More powered clinical trials are needed to evaluate the effects of RAS blockade in renal transplant recipients.

Impact of CT-relevant skeletal muscle parameters on post-liver transplantation survival in patients with hepatocellular carcinoma.

The specific CT-related skeletal muscle parameters predictive of postoperative survival in liver transplant (LT) patients with hepatocellular carcinoma (HCC) remain unclear. There is increasing evidence supporting the role of fatty acids and their lipid intermediates in regulating skeletal muscle mass and function, the relationship between lipoprotein subfractions and body composition remains unclear. Adult patients with HCC who underwent LT between January 2015 and September 2022 were retrospectively analyzed. CT parameters, including skeletal muscle index (SMI), psoas muscle index (PMI), skeletal muscle density (SMD), visceral and subcutaneous adipose tissue (VAT and SAT), and the VAT/SAT ratio at the L3 level, and lipid profiles, were assessed prior to LT. Of the 284 LT patients with HCC, 224 underwent CT (L3 level) within 3months of LT, and 82 (37%) were diagnosed with myosteatosis. Patients with myosteatosis exhibited significantly lower 1- and 3-year survival rates (p = 0.002, p = 0.01), a trend persisting even beyond the Milan criteria (p = 0.004, p = 0.04). After adjusting for covariates, SMD demonstrated a significant negative correlation with post-transplant survival (HR: 0.90, [95% Confidence Interval(CI): 0.83-0.98], C-statistic: 0.78, p = 0.009). Pearson's correlation analysis revealed a positive correlation between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1(ApoA1) levels and SMD. Multivariate stepwise regression analysis demonstrated that every 10 Hounsfield unit decrease in SMD was associated with a 0.16mmol/L decrease in HDL-C and a 0.18g/L decrease in ApoA1. Routine abdominal CT scans for assessing skeletal muscle density before LT were significantly associated with post-transplant mortality. Furthermore, abnormal HDL-C and ApoA1 levels before LT were associated with myosteatosis.

Recent solid-phase microextraction-based analytical approaches for the profiling of biliary bile acids in pre-transplant assessments of liver grafts subjected to normothermic ex vivo liver perfusion

BackgroundLiver transplantation is the definitive treatment for end-stage liver failure, but the scarcity of donor organs remains a significant challenge. Leveraging organs from extended criteria donors (ECD) offers a potential avenue to address worldwide shortages, though these organs are more susceptible to post-reperfusion injury. This study explores the use of normothermic ex vivo liver perfusion (NEVLP) as a method for organ preservation – an approach that sustains liver metabolism and facilitates pre-transplant assessments of organ viability via bile analysis. The focal point of this study revolves on the development of analytical methods for determining the bile acid profile throughout the peritransplantation period as a potential indicator of liver function and viability. ResultsThe study optimized and validated a high-throughput analytical method to quantify selected bile acids in bile samples using a thin-film microextraction-liquid chromatography-mass spectrometry (TFME-LC-MS) platform. Furthermore, it introduced a solid-phase microextraction-microfluidic open interface-mass spectrometry (SPME-MOI-MS) method for rapid direct analysis of bile acid isobar groups. In the animal study, discernible variations in the concentrations of specific bile acids were observed between donors after circulatory death (DCD) and heart-beating donors (HBD), particularly following normothermic perfusion and reperfusion. Noteworthy fluctuations in individual bile acid concentrations were observed throughout the entire organ transplantation process, with taurocholic acid (TCA), glycocholic acid (GCA), and glycochenodeoxycholic acid (GCDCA) emerging as promising indicators of organ quality. The efficacy of the SPME-MOI-MS platform in corroborating these trends highlights its potential for real-time bile acid analysis during liver transplantation procedures. SignificanceOur findings underscore the efficacy of NEVLP in tandem with advanced bile acid analysis methods as a reliable strategy for pre-transplant assessments of organ viability, potentially increasing the use of ECD organs and reducing organ shortages. The ability to monitor bile acid profiles in real-time provides crucial insights into liver function and ischemic injury, making significant strides in improving transplant outcomes and patient survival rates.

Impact of spleen volume on post-allogenic hematopoietic transplant outcomes in myelofibrosis: Utility of 3D volumetrics in splenomegaly.

6558 Background: Splenomegaly is a hallmark of myelofibrosis, thought to be correlated with graft failure and worsened overall survival in transplant patients. Past studies have utilized manual spleen measurement, potentially affecting accuracy. Using 3D volume can more precisely measure spleen size. Hence, the true impact of splenomegaly on transplant outcomes remains unclear. In this retrospective study, we examined myelofibrosis patients who underwent HCT and, using 3D volumetrics, analyzed the impact of splenomegaly and volume reduction over time on post HCT outcomes. Methods: This retrospective study included 130 City of Hope myelofibrosis patients with pre HCT imaging (2004–2023). Patients were divided into pre HCT spleen volume of >3000 cc and <3000 cc, with >3000 cc considered massive splenomegaly. Spleen volume was measured using Vitrea 3D volumetric software. For each patient, depending on imaging available, volume was measured 0-3 months pre HCT, 3-6 months, 6-9 months, and 9-12 months post HCT with corresponding volume reduction calculations. Pre HCT spleen volume was also temporally correlated with several post HCT outcomes. Results: Median age at HCT was 60 (17-75), and 95% of patients received the Fludarabine/Melphalan conditioning regimen. Median spleen volume pre HCT was 1150 cc (41-6695 cc). Sixteen patients measured >3000cc, and 114 patients measured <3000cc. Median spleen volume 3-6 months post HCT was 661 cc (80-1731 cc) with a median 48% volume reduction. The data suggests that majority of volume reduction occurred during this time (table). Five-year overall survival (OS) was 72.8%. Relapse was 11.0% at 1 year and 14.7% at 5 years. NRM at 5 years was 17.3%. ANC engraftment peaked at 28 days at 92.3%. Pre HCT spleen volume (<1000 cc, 1000-2000 cc, >2000 cc) did not have a significant impact on OS (P = 0.992), disease free survival (P = 0.783), relapse (P = 0.187), NRM (P = 0.627), or ANC Engraftment (P = 0.526). There was a statistically insignificant downward trend for platelet engraftment (P = 0.162). For patients with or without massive splenomegaly (>3000cc), there was no significant effect with any of the analyzed post HCT outcomes. Conclusions: This retrospective study includes an analysis of spleen volume by 3D volumetrics, a more accurate measurement of spleen size, and whether it significantly impacts post HCT outcomes. Our data analysis demonstrates that splenomegaly, massive or not, does not significantly impact transplant outcomes for patients receiving a reduced intensity conditioning regimen.[Table: see text]

Erratum: Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients

Erratum: Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients

Kidney transplantation in patients with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a disorder of the mammalian target of the rapamycin (mTOR) pathway associated with the development of multisystem tumors, including renal angiomyolipoma (AML). These renal tumors are benign by nature but locally invasive and carry a risk for the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). The frequency of subsequent renal transplantation in this population is largely uncharacterized, although single-center data suggests that 5%-15% of adult TSC patients are kidney transplant recipients. This retrospective cohort study utilized United Network for Organ Sharing (UNOS) data. We included candidates waitlisted between 1987 and 2020 for a first kidney transplant with TSC-associated kidney failure. We utilized descriptive statistics to characterize the frequency of first-time kidney transplant waitlisting and transplantation among persons with TSC and the Fine-Gray subdistribution hazard model to evaluate characteristics associated with progression from waitlist. We identified 200 TSC-associated kidney failure patients within the waitlist cohort. Of these, 12 were pediatric patients. Two-thirds (N = 134) of waitlisted persons were female. One hundred forty patients received a transplant with a median waitlist time of 2 years. Younger age at waitlisting was associated with a greater probability of progressing to transplant (HR 0.98 [95% CI: 0.96-0.99]). 91.8% of kidney transplant recipients survived 1-year post-transplant with a functioning allograft. The majority of patients with TSC who are waitlisted for a kidney transplant progress onto transplantation with excellent 1-year post transplant patient and allograft survival.

Management and Outcomes of Kidney Transplant Candidates With Severe Pulmonary Hypertension: A Single-center Strategy and Experience.

Severe pulmonary hypertension (PH) is associated with high mortality posttransplant and thus is considered a contraindication to kidney transplantation. In this study, we describe the pretransplant management and posttransplant outcomes in patients with severe PH using a multidisciplinary approach. Between 11 of 2013 and 8 of 2022, we identified all patients with severe PH on initial pretransplant workup who underwent ultrafiltration (UF) or medical therapy for PH before transplant. Posttransplant we evaluated the perioperative course, renal function, graft, and patient survival. We compared survival to those who remained waitlisted or were delisted. Three-two patients (mean age = 55.03 ± 10.22 y) diagnosed with severe PH on pretransplant screening echocardiogram. Thirty patients (94%) were subjected to a median of 4 (range, 3-8) UF sessions with an average weight loss of 4.33 ± 2.6 kg. Repeat assessment of PH revealed a decline in mean pulmonary artery systolic pressure from 67 ± 12 mm Hg to 43 ± 13 mm Hg (P < 0.0001). Seventeen patients (53%) received a kidney transplant. The mean estimated Glomerular Filtration Rate at 3, 6, 9, and 12 mo was 72 ± 27, 72 ± 28, 75 ± 29, and 75 ± 29 mL/min/1.73 m2. Among, those who underwent transplantation both graft and patient survival was 100% at 1-y posttransplant. Overall, since the UF intervention, at a median follow-up of 88 ± 12 mo those transplanted had a patient survival of 88% while those who remained on dialysis had a survival of 53% (P = 0.0003). In this single-center study, we report postcapillary PH can be a significant contributor to elevations in pulmonary artery systolic pressure. Using a multidisciplinary approach, PH can improve with volume removal and phosphodiesterase 5 inhibitors therapy leading to a successful posttransplant outcome.

Outcomes of Kidney Transplantation Among COVID-19 Recovered Patients in a Single Transplant Center

The COVID-19 pandemic significantly lowered kidney transplantation (KT) rates worldwide, and studies regarding outcomes of patients who developed COVID-19 infection before KT are limited, especially in low to middle-income countries. To determine the 1-year graft and patient survival of kidney transplant recipients who recovered from COVID-19 infection before KT. We retrospectively reviewed all adult end-stage renal disease patients who underwent KT at the National Kidney and Transplant Institute from June 2020 through October 2021. Transplant parameters, graft and patient survival, pretransplant COVID-19 infection, and post-KT infectious complications were recorded. Data was analyzed using two-tailed descriptive statistical tests. Of the 219 recipients, 23 (11%) had COVID-19 infection within 1 to 16 months before KT. The mean age of KT recipients was 36 years (range, 25-57), and 61.9% had chronic glomerulonephritis as primary renal disease. The mean duration from COVID-19 recovery to KT was 79 days (range, 21-207). There was no significant difference in the 1-year biopsy-proven acute rejection in the 2 groups, at 4.5% vs 12.5% for the COVID-19 and non-COVID-19 group, respectively. Both the 1-year graft and patient survival were similar in the COVID-19 and non-COVID-19 groups at 98.4% vs 100% and 100% vs 98.44%, respectively. There was no significant difference in biopsy-proven acute rejection, 1-year graft, and patient survival among patients who had a prior COVID-19 infection vs those who did not. Kidney transplantation appears safe when performed at least 1 month from COVID-19 infection.

Spliced CEACAM1: A Potential Novel Biomarker and Target for Ameliorating Liver Ischemia-reperfusion Injury.

Hepatic ischemia-reperfusion injury remains a significant challenge in liver transplantation potentially leading to delayed graft function, primary nonfunction, and sometimes rejection. Understanding the underlying mechanisms and implementing mitigation strategies are essential for improving transplant outcomes and patient survival. A recent study published by Dery et al shows that alternative splicing of carcinoembryonic antigen-related cell adhesion molecule 1 regulated by hypoxia inducible factor 1 alpha under stress enhances hepatic ischemia tolerance in mice and humans. The authors identified a direct binding of hypoxia inducible factor 1 alpha to the promoter region of polypyrimidine tract-binding protein 1 splicing enzyme, resulting in carcinoembryonic antigen-related cell adhesion molecule 1-short induction and improved posttransplant outcomes. This study has notably elucidated a potential biomarker pertaining to the quality of liver transplant donor grafts.

Performance of risk prediction models for post-liver transplant patient and graft survival over time.

Given liver transplantation organ scarcity, selection of recipients and donors to maximize post-transplant benefit is paramount. Several scores predict post-transplant outcomes by isolating elements of donor and recipient risk, including the donor risk index, Balance of Risk, pre-allocation score to predict survival outcomes following liver transplantation/survival outcomes following liver transplantation (SOFT), improved donor-to-recipient allocation score for deceased donors only/improved donor-to-recipient allocation score for both deceased and living donors (ID2EAL-D/-DR), and survival benefit (SB) models. No studies have examined the performance of these models over time, which is critical in an ever-evolving transplant landscape. This was a retrospective cohort study of liver transplantation events in the UNOS database from 2002 to 2021. We used Cox regression to evaluate model discrimination (Harrell's C) and calibration (testing of calibration curves) for post-transplant patient and graft survival at specified post-transplant timepoints. Sub-analyses were performed in the modern transplant era (post-2014) and for key donor-recipient characteristics. A total of 112,357 transplants were included. The SB and SOFT scores had the highest discrimination for short-term patient and graft survival, including in the modern transplant era, where only the SB model had good discrimination (C ≥ 0.60) for all patient and graft outcome timepoints. However, these models had evidence of poor calibration at 3- and 5-year patient survival timepoints. The ID2EAL-DR score had lower discrimination but adequate calibration at all patient survival timepoints. In stratified analyses, SB and SOFT scores performed better in younger (< 40 y) and higher Model for End-Stage Liver Disease (≥ 25) patients. All prediction scores had declining discrimination over time, and scores relying on donor factors alone had poor performance. Although the SB and SOFT scores had the best overall performance, all models demonstrated declining performance over time. This underscores the importance of periodically updating and/or developing new prediction models to reflect the evolving transplant field. Scores relying on donor factors alone do not meaningfully inform post-transplant risk.

CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance, and immune homeostasis

AbstractCPX-351, a liposomal combination of cytarabine plus daunorubicin, has been approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes, because it improves survival and outcome of patients who received hematopoietic stem cell transplant compared with the continuous infusion of cytarabine plus daunorubicin (referred to as “7 + 3” combination). Because gut dysbiosis occurring in patients with AML during induction chemotherapy heavily affects the subsequent phases of therapy, we have assessed whether the superior activity of CPX-351 vs “7 + 3” combination in the real-life setting implicates an action on and by the intestinal microbiota. To this purpose, we have evaluated the impact of CPX-351 and “7 + 3” combination on mucosal barrier function, gut microbial composition and function, and antifungal colonization resistance in preclinical models of intestinal damage in vitro and in vivo and fecal microbiota transplantation. We found that CPX-351, at variance with “7 + 3” combination, protected from gut dysbiosis, mucosal damage, and gut morbidity while increasing antifungal resistance. Mechanistically, the protective effect of CPX-351 occurred through pathways involving both the host and the intestinal microbiota, namely via the activation of the aryl hydrocarbon receptor–interleukin-22 (IL-22)–IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes. This study reveals how the gut microbiota may contribute to the good safety profile, with a low infection-related mortality, of CPX-351 and highlights how a better understanding of the host-microbiota dialogue may contribute to pave the way for precision medicine in AML.

Reduced graft survival in renal transplant patients with urinary tract infections - a meta-analysis.

Renal transplant patients are prone to developing urinary tract infections (UTIs). However, the potential effect of a UTI on renal graft loss remains unclear. We systematically surveyed the literature for a potential association between UTI and graft loss. Articles were identified in online databases using a specific search string, followed by post selection for meta-analysis following four inclusion criteria: 1) a clear definition of UTI and recurrent UTI, 2) n > 200, 3) patient age > 16 years and 4) inclusion of data on graft loss. Data on UTI and graft loss were extracted from the included studies for calculation of a combined weighted odds ratio (OR) using the Mantel-Haenszel method. This review was conducted according to the PRISMA 2020 statement. Unfortunately, only eight of 108 papers met the inclusion criteria. These studies reported between 276 and 2,368 patients, primarily male, aged around 50 years. The two-year incidence of overall UTI varied from 16.5% at a 27.5-month follow-up to 30.1% at a 24-month follow-up from transplantation. Seven papers were included in the OR analysis; two found an association between UTI and graft loss and five did not. However, in the meta-analysis, the weighted OR for all seven studies was 1.340 (95% confidence interval: 1.050-1.720). Filtering the literature for a strict definition of UTI allowed us to establish an association between UTI and graft loss in renal transplant patients. However, further investigation and stronger studies using the Goldman criteria are needed to allow stratification for UTI severity and effect on graft loss.

Syk/BLNK/NF-κB signaling promotes pancreatic injury induced by tacrolimus and potential protective effect from rapamycin

BackgroundThe treatment of tacrolimus-induced post-transplantation diabetes mellitus (PTDM) has become a hot topic to improve the long-term survival of organ transplant patients, however whose pathogenesis has not been fully elucidated. In pancreas, the up-regulation of NF-κB has been reported to stimulate cytokine IL-1β/TNF-α secretion, inducing pancreatic injury, meanwhile other studies have reported the inhibitory effect of rapamycin on NF-κB. PurposeThe aim of this study was to clarify the mechanism of tacrolimus-induced pancreatic injury and to explore the potential effect from small dose of sirolimus. MethodsWistar rats were randomly divided normal control (NC) group, PTDM group, sirolimus intervention (SIR) group. Transcriptomic analysis was used to screen potential mechanism of PTDM. Biochemical index detections were used to test the indicators of pancreatic injury. Pathological staining, immumohistochemical staining, immunofluorescent staining, western blot were used to verify the underlying mechanism. ResultsCompared with NC group, the level of insulin was significant reduction (P < 0.01), inversely the level of glucagon was significantly increase (P < 0.01) in PTDM group. Transcriptomic analysis indicated Syk/BLNK/NF-κB signaling was significantly up-regulated in PTDM group. Pathological staining, immumohistochemical staining, immunofluorescent staining, western blot verified Syk/BLNK/NF-κB and TNF-α/IL-1β were all significantly increased (P < 0.05 or P < 0.01), demonstrating the mechanism of tacrolimus-induced pancreatic injury via Syk/BLNK/NF-κB signaling. In addition, compared with PTDM group, the levels of weight, FPG, AMY, and GSP in SIR group were significant ameliorative (P < 0.05 or P < 0.01), and the expressions of p-NF-κB, TNF-α/IL-1β in SIR group were significantly reduction (P < 0.05 or P < 0.01), showing Syk/BLNK/NF-κB signaling promoted pancreatic injury induced by tacrolimus and potential protective effect from rapamycin reducing NF-κB. ConclusionSyk/BLNK/NF-κB signaling promotes pancreatic injury induced by tacrolimus and rapamycin has a potentially protective effect by down-regulating NF-κB. Further validation and clinical studies are needed in the future.

The value of functional magnetic resonance imaging in evaluating renal allograft function

BackgroundTo explore the value of arterial spin labeled (ASL) and blood oxygen level dependent (BOLD) imaging in evaluating allogeneic kidney function after renal transplantation. MethodsOne hundred and thirty-five renal transplant patients were included. Demographic and imaging data were collected. Transplanted renal function, pathology, ASL and BOLD parameters were obtained. The patients were divided into normal, mild and severe injury group. The correlation between BOLD/ASL parameters and clinical data were evaluated. The prediction models were based on ASL and BOLD parameters using multivariate logistic analysis. Cox proportional hazards regression model was used to analyze the effects of gender, age, ASL and BOLD on the survival of renal transplant patients. ResultsASL and BOLD parameters were independently associated with renal function injury and renal allograft positive pathology. The AUC of prediction model for renal allograft function based on ASL and BOLD parameters was 0.85, while the AUC based on BOLD parameters was 0.70. Renal transplantation time showed a positive correlation with age, BOLD parameters and SCr，while a negative correlation with ASL parameters and eGFR. ASL parameter was positively correlated with eGFR and negatively correlated with Scr. BOLD parameter was negatively correlated with eGFR, ASL and positively correlated with Scr. Cox proportional hazards regression model showed that the increase of age could reduce the risk of renal function injury and positive pathology. ConclusionsASL and BOLD were associated with renal function injury and renal allograft positive pathology. ASL and BOLD had some value in predicting renal allograft function.

Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients.

The prevalence of malnourished patients before transplantation and the influence of malnutrition on graft and patient outcomes remain underestimated, despite being associated with higher postoperative morbidity and mortality. This study aimed to develop an easy nutritional screening tool and evaluate the impact of nutritional status on clinical outcome, graft survival (GS) and mortality risk in kidney transplant patients (KTP). In this retrospective cohort study including 451 KTP, we developed a score by using anthropometric, clinical, and laboratory measures performed in the pretransplant evaluation. The patients were stratified into 3 groups according to the final score: G1 (0 or 1 point)=low risk, G2 (2 to 4 points)=moderate risk, and G3 (>5 points)=high risk of malnutrition. The patients were monitored after transplantation at least 1 to 10 years. Stratifying the 451 patients based on the pretransplant risk score, G1, G2, and G3 were composed of 90, 292, and 69 patients, respectively. Patients from G1 maintained the lowest serum creatinine levels at hospital discharge when compared with others (p = 0.012). The incidence of infection in the patients from G3 was higher than patients from G1 and G2 (p = 0.030). G3 recipients showed worse GS than G1 patients (p = 0.044). G3 patients showed almost threefold higher risk for graft loss (HR 2.94, 95% CI 1.084-7.996). KTP with higher malnutrition risk score were associated with worse outcomes and GS. The nutritional screening tool is easy to be used in clinical practice to evaluate the patient in preparation for kidney transplant.

Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients

RESUMO Antecedentes: A prevalência de pacientes desnutridos antes do transplante e a influência da desnutrição nos desfechos do enxerto e do paciente permanecem subestimadas, embora estejam associadas a maior morbimortalidade pós-operatória. Este estudo buscou desenvolver uma ferramenta simples de triagem nutricional e avaliar o impacto do estado nutricional no desfecho clínico, sobrevida do enxerto (SE) e risco de mortalidade em pacientes transplantados renais (PTR). Métodos: Neste estudo de coorte retrospectivo incluindo 451 PTR, desenvolvemos um escore usando medidas antropométricas, clínicas e laboratoriais tomadas na avaliação pré-transplante. Os pacientes foram estratificados em 3 grupos segundo a pontuação final: G1 (0-1 ponto) = baixo risco, G2 (2-4 pontos) = risco moderado e G3 (&gt;5 pontos) = alto risco de desnutrição. Eles foram monitorados por pelo menos 1 a 10 anos após o transplante. Resultados: Os 451 pacientes foram estratificados em G1, G2 e G3, que consistiram em 90, 292 e 69 pacientes, respectivamente. Os pacientes do G1 mantiveram os menores níveis de creatinina sérica na alta hospitalar em relação aos demais (p = 0,012). A incidência de infecção nos pacientes do G3 foi maior que nos pacientes do G1 e G2 (p = 0,030). Os pacientes do G3 apresentaram SE pior do que os pacientes do G1 (p = 0,044) e um risco quase três vezes maior de perda do enxerto (HR 2,94; IC 95% 1,084-7,996). Conclusões: PTR com maior escore de risco de desnutrição foram associados a piores desfechos e menor SE. A ferramenta de triagem nutricional é fácil de usar na prática clínica para avaliar pacientes em preparação para transplante renal.