Risk Of Graft Loss Research Articles

Mechanism, Potential, and Concerns of Immunotherapy for Hepatocellular Carcinoma and Liver Transplantation.

In the last decade, immunotherapy (IT) has revolutionized oncology and found indications in many cancers, including hepatocellular carcinoma (HCC). In HCC, IT has become the leading systemic therapy for advanced diseases. At the same time, it carries the promise of being a valuable therapy in other settings, including intermediate-stage and unresectable disease, as a downstaging or conversion modality. More controversial is the role of IT in relationship to liver transplantation (LT): on one side, it could be a helpful tool to control or downstage HCC before LT or to treat tumor recurrence after LT, while on the other, it carries the risk of graft rejection and graft loss. This review aims to cover these concerns in depth and unravel the current literature.

Assessing Patients beyond the Simple Optics of BMI: The Concomitant Role of Sarcopenia and BMI in Predicting Kidney Transplant Outcomes.

Body composition is associated with prognosis in many clinical settings, and patients undergoing kidney transplantation are often high risk with multiple comorbidities. We aimed to assess the effect of sarcopenia and body composition on transplant outcomes. We performed a retrospective analysis of 274 kidney transplants with CT scans within 3 years of transplantation. The skeletal muscle index (SMI) at the L3 vertebrae was used to evaluate sarcopenia (SMI < 40.31 cm2/m2 in males, <30.88 cm2/m2 in females). Sarcopenia, body mass index (BMI), and the visceral-to-subcutaneous-fat ratio (VSR) were assessed separately. We also used a composite BMI/sarcopenia measurement in four patient groups: BMI < 25/Non-Sarcopenic, BMI < 25/Sarcopenic, BMI > 25/Non-Sarcopenic, and BMI > 25/Sarcopenic. The outcomes measured were eGFR (1 and 3 months; and 1, 3, and 5 years), delayed graft function (DGF), rejection, major adverse cardiovascular events (MACE), and post-operative complications. Sarcopenia was associated with an increased 1-year risk of MACE (OR 3.41, p = 0.036). BMI alone had no effect on function, DGF, MACE, or on other complications. High VSR was associated with a lower risk of DGF (OR 0.473, p = 0.016). When sarcopenia and BMI were assessed together, the BMI > 25/sarcopenic patients had the poorest outcomes, with increased risk of MACE (OR 26.06, p = 0.001); poorer eGFR at 1, 3, 12, and 36 months; (p < 0.05 at all timepoints), and poorer graft survival (p = 0.002). Sarcopenia alone is associated with an increased risk of MACE. Overweight sarcopenic patients are additionally at increased risk of graft loss and have poorer graft function for up to three years.

Kidney transplantation in multiple myeloma in 2023: A short review.

Patients with multiple myeloma (MM) frequently present with kidney involvement, of which a non-negligible proportion will progress to end-stage kidney disease. Kidney transplantation (KT) is the preferred kidney replacement therapy for selected patients; however, there are still many uncertainties regarding its application in MM patients. The risk of hematological relapse and subsequent graft loss or patient death often leads nephrologists to deem these patients unfit for KT. As such, data on KT in MM patients are heterogeneous and originate from individual case reports and small case series. Although MM is still an incurable disease, the addition of newer drugs and autologous hematopoietic stem cell transplant (HSCT) in the standard of care has been increasing patients' overall survival in recent decades. Risk stratification using cytogenetic studies and minimal residual disease detection are helpful in assessing the risk of relapse in patients who attain a complete response after HSCT. The greatest challenges remain the correct identification of patients who will most probably benefit from KT from a survival perspective and the determination of how long relapse-free survival should be before the transplant is performed.

A retrospective study investigating the risk of graft loss in living donor liver transplant cases where size mismatching is predicted from graft-to-recipient weight ratio.

Living donor liver transplantation (LDLT) is vital for pediatric end-stage liver disease due to organ shortages. The graft-to-recipient weight ratio (GRWR) preoperatively measured predicts the outcomes of LDLT. We typically target between 0.8 and 3.0-4.0%, but the ideal GRWR remains controversial. We compared the outcomes of LDLT according to the GRWR to examine whether the criteria could be expanded while ensuring safety. We retrospectively reviewed 99 patients who underwent LDLT in our department by dividing them into three groups according to their GRWR: Group S, with GRWR values lower than the normal range (GRWR < 0.8%); Group M, with GRWR values in the normal range (GRWR ≥ 0.8 to < 3.5%); and Group L, with GRWR values above the normal range (GRWR ≥ 3.5%). In Groups S and L, 46.2 and 44.4% of patients underwent splenectomy and delayed abdominal wall closure, respectively. After these intraoperative adjustments, there were no significant differences between the groups in 5-year patient survival, 5-year graft survival, or the occurrence of post-transplantation thrombosis. When the GRWR is beyond the normal threshold, the risk of complications associated with graft size might be reduced by adjustments to provide appropriate portal blood flow and by delayed abdominal wall closure.

Antibody-Mediated Rejection in Lung Transplantation: Diagnosis and Therapeutic Armamentarium in a 21st Century Perspective.

Humoral immunity is a major waypoint towards chronic allograft dysfunction in lung transplantation (LT) recipients. Though allo-immunization and antibody-mediated rejection (AMR) are well-known entities, some diagnostic gaps need to be addressed. Morphological analysis could be enhanced by digital pathology and artificial intelligence-based companion tools. Graft transcriptomics can help to identify graft failure phenotypes or endotypes. Donor-derived cell free DNA is being evaluated for graft-loss risk stratification and tailored surveillance. Preventative therapies should be tailored according to risk. The donor pool can be enlarged for candidates with HLA sensitization, with strategies combining plasma exchange, intravenous immunoglobulin and immune cell depletion, or with emerging or innovative therapies such as imlifidase or immunoadsorption. In cases of insufficient pre-transplant desensitization, the effects of antibodies on the allograft can be prevented by targeting the complement cascade, although evidence for this strategy in LT is limited. In LT recipients with a humoral response, strategies are combined, including depletion of immune cells (plasmapheresis or immunoadsorption), inhibition of immune pathways, or modulation of the inflammatory cascade, which can be achieved with photopheresis. Altogether, these innovative techniques offer promising perspectives for LT recipients and shape the 21st century's armamentarium against AMR.

Systematic Review and Meta-Analysis of the Outcomes After Hepatic Artery Reconstruction in Pediatric Liver Transplantation Using a Microscope Versus Surgical Loupe

BackgroundTo review the impact of the operating microscope (OM) for reconstruction of the hepatic artery (HA) by comparing the outcomes with standard loupe reconstruction (SL) in pediatric liver transplantation (LT). MethodsStudies comparing the application of OM and SL for the reconstruction of the HA in primary pediatric LT were included from a systematic search of MEDLINE, Cochrane Library and EMBASE from inception to June 2022. Re-transplantation, dual grafts and auxiliary transplants were excluded. Primary outcome was the rate of HA thrombosis (HAT). Secondary outcomes were graft loss and mortality. ResultsThere were 1261 liver recipients from 9 included studies published until June 2022. There were 484 patients in the OM group and 777 patients in the SL group. HAT incidence with OM was significantly lower with OR = 0.18 (95% CI: 0.07-0.48). The 1-year graft survival was significantly better in the OM group with OR = 2.77 (95% CI: 1.13-6.80). 1-year overall mortality was also significantly lower with OM with OR = 0.39 (0.18-0.86). The use of OM did not significantly impact the incidence of HAT in the living donor liver transplant subgroup. Differences in time for hepatic HA reconstruction, total operating time and length of hospital stay did not reach statistical significance. ConclusionThe use of OM has reduced the risk of HAT, graft loss and mortality in pediatric liver transplantation. Adoption of microsurgical principles in general may have contributed to the improved outcomes with SL reconstruction of HA in pediatric LT.

Adverse Pregnancy Outcomes in Solid Organ Transplant Recipients

Transplant recipients experience high rates of adverse pregnancy outcomes; however, contemporary estimates of the association between solid organ transplantation and adverse pregnancy outcomes are lacking. To evaluate the association between solid organ transplantation and adverse pregnancy outcomes and to quantify the incidence of allograft rejection and allograft loss during pregnancy. PubMed/MEDLINE, EMBASE and Scopus databases were searched from January 1, 2000, to June 20, 2024, and reference lists were manually reviewed. Cohort and case-control studies that reported at least 1 adverse pregnancy outcome in pregnant women with solid organ transplantation vs without solid organ transplant or studies that reported allograft outcomes in pregnant women with solid organ transplantation were included following independent dual review of abstracts and full-text articles. Two investigators abstracted data and independently appraised risk of bias using the Newcastle Ottawa Scale. A random-effects model was used to calculate overall pooled estimates using the DerSimonian-Laird estimator. Reporting followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Primary pregnancy outcomes were preeclampsia, preterm birth (<37 weeks), and low birth weight (<2500 g). Secondary pregnancy outcomes were live birth rate, gestation, very preterm birth (<32 weeks), very low birth weight (<1500 g), and cesarean delivery. Allograft outcomes were allograft loss and rejection during pregnancy. Data from 22 studies and 93 565 343 pregnancies (4786 pregnancies in solid organ transplant recipients) were included; 14 studies reported adverse pregnancy outcomes, and 13 studies provided data for allograft outcomes. Pregnancies in organ transplant recipients were associated with significantly increased risk of preeclampsia (adjusted odds ratio [aOR], 5.83 [95% CI, 3.45-9.87]; I2 = 77.4%), preterm birth (aOR, 6.65 [95% CI, 4.09-12.83]; I2 = 81.8%), and low birth weight (aOR, 6.51 [95% CI, 2.85-14.88]; I2 = 90.6%). The incidence of acute allograft rejection was 2.39% (95% CI, 1.20%-3.96%; I2 = 68.5%), and the incidence of allograft loss during pregnancy was 1.55% (95% CI, 0.05%-4.44%; I2 = 69.2%). In this systematic review and meta-analysis, pregnancies in recipients of a solid organ transplant were associated with a 4 to 6 times increased risk of preeclampsia, preterm birth, and low birth weight during pregnancy. There was a low overall risk of graft rejection or loss during pregnancy.

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

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

Chimeric HLA antibody receptor T cell therapy for humoral transplant rejection.

Antibody-mediated rejection (ABMR) is a significant obstacle to achieving optimal long-term outcomes after solid organ transplantation. The presence of donor-specific antibodies (DSA), particularly against HLA, increases the risk of allograft rejection and subsequent graft loss. No effective treatment of ABMR currently exists, warranting novel approaches to target the HLA-specific humoral alloimmune response. Cellular therapies may hold promise to this end. According to publicly available sources as of now, three independent laboratories have genetically engineered a chimeric HLA-antibody receptor (CHAR) and transduced it into human T cells, based on the demonstrated efficacy of chimeric antigen receptor T cell therapies in malignancies. These CHAR-T cells are designed to exclusively eliminate B cells that produce donor-specific HLA antibodies, which form the cornerstone of ABMR. CHAR technology generates potent and functional human cytotoxic T cells to target alloreactive HLA-specific B cells, sparing B cells with other specificities. Thus, CHAR technology may be used as a selective desensitization protocol and to treat antibody-mediated rejection after solid organ transplantation.

Perioperative Fluid Management in Paediatric Liver Transplantation: A Systematic Review.

Perioperative fluid management remains a challenging aspect of paediatric liver transplantation (LT) because of the risk of postoperative complications and haemodynamic instability. Limited research has specifically investigated the impact of fluid management and transfusion on mortality and morbidity in pediatric LT patients. This systematic review summarizes the evidence regarding perioperative fluid management and its clinical outcomes in paediatric LT patients. All primary studies published in English evaluating perioperative fluid management in paediatric LT patients were eligible. PubMed, EBSCOHost, Embase, Proquest, and Google Scholar databases were searched from inception to December 19, 2023. Risks of bias were assessed using the Joanna-Briggs Institute checklist. The results were synthesized narratively. Five retrospective cohort studies of good-excellent quality were included in this review. Two studies evaluated intraoperative fluid administration, one study compared postoperative fluid balance (FB) with outcomes, and two studies compared massive versus non-massive transfusion. A higher mortality rate was associated with intravenous lactated ringer's (LR) than with normal saline, but not with massive transfusion (MT). Longer hospital stays were correlated with MT, >20% positive FB in the first 72 hours, and greater total intraoperative blood product administration. Higher intraoperative fluid administration was associated with a greater thrombotic risk. Additionally, intraoperative MT and lR infusion were associated with an increased risk of 30-day graft loss and graft dysfunction, respectively. Fluid management may impact the outcomes of paediatric LT recipients. These findings underscore the need for more studies to explore the best fluid management and evaluation strategies for children undergoing LT.

IgA nephropathy recurrence after living donor kidney transplantation: a retrospective analysis of postoperative outcomes at a single high-volume transplant center

BackgroundIgA nephropathy (IgAN) is a common primary glomerulonephritis leading to end-stage renal disease. Living donor kidney transplantation (LDKT) is considered a favorable treatment option, but IgAN recurrence rates and the impact on outcome is unclear. In the present study, we retrospectively analyzed the rate of IgAN recurrence, risk factors and clinical outcomes in LDKT recipients.MethodsWe analyzed 193 adult patients who received a LDKT between 2011 and 2017 of which 32 (16.7%) had IgAN as underlying disease. Demographic data and clinical outcomes, especially regarding IgAN recurrence, were evaluated. Mean follow-up period was 102.13 months in the IgAN group vs. 97.27 months in the control group.ResultsAmong the IgAN cohort, five (15.63%) experienced IgAN recurrence. Patients with IgAN underwent LDKT at a significantly younger age (p < 0.001). No significant differences were observed in demographic factors, HLA-mismatches, or AB0-compatibility. Patients receiving an immunosuppressive regimen including Cyclosporine A (60% vs. 7.4%) instead of Tacrolimus (40% vs. 92.6%) were significantly more likely to develop IgAN recurrences (p < 0.001). Moreover, early post-surgery serum creatinine levels were higher in the recurrence group at one week (4.25 vs. 1.65 mg/dl; p < 0.001), one month (2.13 vs. 1.53 mg/dl; p = 0.027) and two years (2.65 vs. 1.34 mg/dl; p = 0.008). Although graft survival displayed a tendency towards inferior outcomes after recurrence, significance was not reached (p = 0.14, log-rank test).ConclusionLiving donor kidney transplantation continues to be recommended as the preferred treatment option for IgAN patients, despite the potential risk of recurrence and graft loss.

Unmasking the Silent Threat: COVID-19's Pervasive Impact on Renal Allografts.

Growing evidence has highlighted the substantial effects of COVID-19 on kidneys, ranging from mild proteinuria to severe acute kidney injury. However, comprehensive assessments of histopathological features in renal allograft biopsies are lacking. Seventeen kidney transplant recipients with COVID-19 between March 2020 and November 2022 were evaluated. Clinical characteristics, pathological findings, and outcomes were studied. Six kidney transplant recipients (35.3%) developed acute kidney injury, leading to the requirement for hemodialysis. COVID-19 severity, as indicated by pneumonia (P = .028) and hospitalization (P = .002), was significantly associated with development of acute kidney injury. Most patients with COVID-19 (82.4%) showed considerably increased proteinuria levels (82.4%), along with presence of new-onset microscopic hematuria (35.3%) and nephrotic syndrome (58.8%). Tubular viral inclusionlike changes were detected in 47.1% of cases and were associated with a higher risk of graft loss (75%). Thrombotic microangiopathy and endothelial cell swelling in glomeruli were prevalent, highlighting extensive endothelial cell injury. Most recipients (88.2%) experienced rejection after COVID-19, with graft loss occurring in 46.7% of these cases. Biopsies revealed collapsing (n = 5), noncollapsing (n = 3), and recurrent (n = 2) focal segmental glomerulosclerosis, as well as acute tubulointerstitial nephritis (n = 3), crescentic glomerulonephritis with immunoglobulin A nephropathy (n = 1), and membranoproliferative glomerulonephritis (n = 1), in 129.7 ± 33 days. Eight patients experienced graft loss (8.2 ± 2 mo posttransplant). Hospitalization (P = .044) and viralinclusion-like nuclear changes in tubules (P = .044) significantly influenced graft survival. Collapsing (60%) and noncollapsing (66.7%) focal segmental glomerulosclerosis increased the risk of graft loss. COVID-19 has had a multifaceted and enduring effect on renal allografts, urging the need for meticulous monitoring and tailored management strategies to mitigate the risk of severe kidney-related complications and graft loss in this vulnerable population.

ACEI/ARB use within one year of kidney transplant is associated with less AKI and graft loss in elderly recipients

BackgroundOptimizing long-term graft survival remains a major focus in transplant. Elderly kidney transplant recipients are vulnerable to acute kidney injury (AKI) and graft loss. This study assessed the safety and efficacy of ACEI/ARB in elderly kidney transplant recipients and impact on graft outcomes. MethodsRetrospective, longitudinal, cohort study of 500 patients age ≥60 years, who underwent kidney transplantation between 2005 and 2015. Demographic, transplant, and outcomes data were collected. Manual chart abstraction was conducted to determine medication use at discharge, one, three, and five years post-transplant. Univariate and multivariable Cox regression modeling were used to analyze outcomes. ResultsMean age of subjects was 66 years (range 60–81). 59% were males and 50% were African-American. 49% had chronic kidney disease (CKD) due to diabetes mellitus (DM). A total of 38, 134, 167, and 112 elderly kidney transplant recipients were on ACEI/ARB at discharge, one, three, and five years post-transplant respectively. ACEI/ARB initiated within one year of transplant was associated with lower risk of graft loss (HR=0.62, CI 0.38–0.99, p = 0.047). This was driven mainly by a lower risk of death (HR=0.41, CI 0.24–0.71, p = 0.002). ACEI/ARB use was associated with lower risk of AKI after 1 year (HR 0.70, CI 0.52–0.95, p = 0.02). ACEI/ARB was not associated with increased risk of acute rejection or hospitalization. ConclusionInitiation of ACEI/ARB within one year of transplant is associated with lower risk of AKI and graft loss, driven by lower risk of death in elderly kidney transplant recipients. Clinicians should maximize ACEI/ARB therapy early on after kidney transplant.

Changes in Numbers of Glomerular Macrophages Between Two Consecutive Biopsies and the Association With Renal Transplant Graft Survival.

Macrophages are involved in kidney transplants. The aim of the study was to investigate if changes exist in the levels of glomerular macrophage index (GMI) between two consecutive kidney transplant biopsies, and if so to determine their potential impact on graft survival. Two consecutive biopsies were performed on the same renal graft in 623 patients. GMI was categorized into three GMI classes: ≤1.8 Low, 1.9-4.5 Medium, and ≥4.6 High. This division yielded nine possible switches between the first and second biopsies (Low-Low, Low-Medium, etc.). Cox-regressions were used and hazard ratios (HR) with 95% confidence interval (CI) are presented. The worst graft survival was observed in the High-High group, and the best graft survival was observed in the Low-Low and High-Low groups. Compared to the High-High group, a reduction of risk was observed in nearly all other decreasing groups (reductions between 65% and 80% of graft loss). After adjustment for covariates, the risk for graft-loss was lower in the Low-Low (HR = 0.24, CI 0.13-0.46), Low-Medium (HR = 0.25, CI 0.11-0.55), Medium-Low (HR = 0.29, CI 0.11-0.77), and the High-Low GMI (HR = 0.31, CI 0.10-0.98) groups compared to the High-High group as the reference. GMI may change dynamically, and the latest finding is of most prognostic importance. GMI should be considered in all evaluations of biopsy findings since high or increasing GMI levels are associated with shorter graft survival. Future studies need to consider therapeutic strategies to lower or maintain a low GMI. A high GMI besides a vague histological finding should be considered as a warning sign requiring more frequent clinical follow up.

Longitudinal monitoring of Torque Teno virus DNAemia in kidney transplant recipients correlates with long-term complications of inadequate immunosuppression.

Optimization of individual immunosuppression, which reduces the risks of both graft loss and patients' death, is considered the best approach to improve long-term outcomes of renal transplantation. Torque Teno Virus (TTV) DNAemia has emerged as a potential biomarker reflecting the depth of therapeutic immunosuppression during the initial year post-transplantation. However, its efficacy in long-term monitoring remains uncertain. In a cohort study involving 34 stable kidney transplant recipients and 124 healthy volunteers, we established lower and upper TTV DNAemia thresholds (3.75-5.1 log10 cp/mL) correlating with T-cell activatability, antibody response against flu vaccine, and risk for subsequent serious infections or cancer over 50 months. Validation in an independent cohort of 92 recipients confirmed that maintaining TTV DNAemia within this range in >50% of follow-up time points was associated with reduced risks of complications due to inadequate immunosuppression, including de novo DSA, biopsy-proven antibody-mediated rejection, graft loss, infections, or cancer. Multivariate analysis highlighted "in-target" TTV DNAemia as the sole independent variable significantly linked to decreased risk for long-term complications due to inadequate immunosuppression (odds ratio [OR]: 0.27 [0.09-0.77]; p = 0.019). Our data suggest that the longitudinal monitoring of TTV DNAemia in kidney transplant recipients could help preventing the long-term complications due to inadequate immunosuppression.

Diagnostic and Prognostic Value of Machine Perfusion Biomarkers in Kidney Graft Evaluation

BackgroundWith the rising prevalence of end-stage kidney disease, the use of expanded criteria donor allografts, seen as essential for meeting organ demand, still proves challenging due to their higher risk of graft loss, delayed function, and rejection. Machine perfusion, a technique in preserving allografts, offers improved allograft outcomes compared to static cold storage while allowing for the noninvasive measurement of kidney injury biomarkers in the perfusate solution. This offers an objective method to assess graft function at various preservation stages. Materials and MethodsWe conducted a narrative review of the databases PubMed and Scopus, including studies written in the English language and published after 2010. ResultsIn this narrative review, we identified biomarkers, like 4-hydroxyproline, taurine, and glutathione transferase, as predictive markers of delayed graft function. Additionally, biomarkers, like extracellular histone h3, vascular cell adhesion protein, and matrix metalloprotease protein, have shown correlation with decreased graft function, although their predictive ability remains inconclusive. DiscussionThe review outlines various suggestions for potential areas of research focus to enhance future expanded criteria donor allograft utilization. However, limitations exist, including the absence of a singular reliable biomarker and the challenges of validating biomarker effectiveness across diverse outcomes.

Oxalate Nephropathy After Kidney Transplantation: Risk Factors and Outcomes of Two Phenotypes.

Describing risk factors and outcomes in kidney transplant recipients with oxalate nephropathy (ON) may help elucidate the pathogenesis and guide treatment strategies. We used a large single-center database to identify patients with ON and categorized them into delayed graft function with ON (DGF-ON) and late ON. Incidence density sampling was used to select controls. A total of 37 ON cases were diagnosed between 1/2011 and 1/2021. DGF-ON (n=13) was diagnosed in 1.05% of the DGF population. Pancreatic atrophy on imaging (36.4% vs. 2.9%, p=0.002) and gastric bypass history (7.7% vs. 0%; p=0.06) were more common in DGF-ON than with controls with DGF requiring biopsy but without evidence of ON. DGF-ON was not associated with worse graft survival (p=0.98) or death-censored graft survival (p=0.48). Late ON (n=24) was diagnosed after a mean of 78.2 months. Late ON patients were older (mean age 55.1 vs. 48.4 years; p=0.02), more likely to be women (61.7% vs. 37.5%; p=0.03), have gastric bypass history (8.3% vs. 0.8%; p=0.02) and pancreatic atrophy on imaging (38.9% vs. 13.3%; p=0.02). Late ON was associated with an increased risk of graft failure (HR 2.0; p=0.07) and death-censored graft loss (HR 2.5; p=0.10). We describe two phenotypes of ON after kidney transplantation: DGF-ON and late ON. Our study is the first to our knowledge to evaluate DGF-ON with DGF controls without ON. Although limited by small sample size, DGF-ON was not associated with adverse outcomes when compared with controls. Late ON predicted worse allograft outcomes.

#2536 Bisphosphonates as a tacrolimus-sparing strategy in kidney transplantation: insights from a retrospective analysis

Abstract Background and Aims The chronic toxicity of tacrolimus makes its sparing a crucial consideration for kidney transplant recipients (KTRs). Previous research has indicated a positive association between bisphosphonate use and favorable graft outcomes in KTRs. Therefore, our study aimed to investigate whether bisphosphonate use impacts the relationship between tacrolimus trough levels (TTLs) and graft outcomes in KTRs. Method We conducted a retrospective study encompassing 1,657 KTRs who were administered tacrolimus-based immunosuppressive therapy. The primary exposure was characterized by a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and the use of bisphosphonate. The study had two primary outcomes: (1) overall graft loss, defined as either the occurrence of patient death or conversion to kidney replacement therapy, and (2) reaching an estimated glomerular filtration rate (eGFR) of less than 30 ml/min/1.73 m². Results Over a cumulative total of 11,211.8 person-years, overall graft loss were observed in 183 patients, equating to 11.0% of the cohort. In multivariable Cox regression analysis, it was noted that normal to high TTLs, in the absence of bisphosphonate use, were associated with a reduced risk of overall graft loss (HR, 0.61; 95% CI, 0.43-0.87) compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal to high TTLs correlated with an even further diminished risk of overall graft loss (HR, 0.36; 95% CI, 0.16-0.83) in comparison to low TTLs without bisphosphonate use. In low TTLs, the administration of bisphosphonates was associated with a reduced risk of overall graft loss than bisphosphonate non-use (HR, 0.26; 95% CI, 0.14-0.49). Similarly, this trend was observed in cases where the eGFR was below 30 ml/min/1.73 m². Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with a low TTLs. Incorporating bisphosphonate to a conventional immunosuppressant regimen Could potentially reduce tacrolimus requirement.

#1992 Triglyceride-glucose index and risk of cardiovascular events, graft loss and new onset diabetes after transplantation in renal transplant recipients

Abstract Background and Aims Insulin resistance is prevalent disorder, but its clinical significance remains undetermined in renal transplant recipients. We explored the clinical implication of triglyceride-glucose (TyG) index in renal transplant recipients, recognizing it as a valuable marker for insulin resistance. Method A total of 6354 renal transplant recipients were enrolled from a nationwide, prospective cohort between May 2014 and December 2022. The TyG index was assessed between 6- and 12-months post-transplantation. We evaluated the association between TyG index and the risk of composite of cardiovascular events and death, renal allograft loss, and new onset diabetes after transplantation (NODAT). Results During the mean follow-up period of 39.2 ± 26.1 months, a total of 106 composite events of cardiovascular events and death, 174 events of renal allograft loss, and 438 events of NODAT were observed. The cumulative rate for composite events, graft loss, and NODAT was greater in patients with higher TyG quartile (all P &amp;lt; 0.001). In multivariate analysis, higher quartile of TyG was associated with an increased risk of composite events (HR 1.81, 95% CI 1.14–2.86), renal allograft loss (HR 2.13, 95% CI 1.28–3.55), and NODAT (HR 2.52, 95% CI 1.90–3.34). Higher quartile of TyG was associated with future graft dysfunction (adjusted mean eGFR differences of −4.72, 95% CI −7.39 – −2.04). There was a linear escalation in the risk of composite events and graft loss with the incremental rise in the TyG index, concomitant with an exponential augmentation in the risk of NODAT. Conclusion Renal transplant recipients with higher TyG index are associated with higher risk of composite of cardiovascular event and death, renal allograft loss, and NODAT.

#1474 COVID-19-infection in kidney transplant recipients during the omicron surge, a sigh of relief

Abstract Background and Aims The COVID-19 pandemic had a profound impact on global health, particularly affecting high-risk individuals such as solid organ transplant recipients (SOTRs). SOTRs have an elevated risk of severe COVID-19 disease and increased mortality. Kidney transplant recipients (KTRs) vaccinated with mRNA-based vaccines exhibit a lower response rate and shorter half-time of the serologic conversion. However, the percentage of serologic response improves with increasing number of vaccine doses. Studies also indicate that KTRs with prior COVID-19 infection demonstrate a more robust immune response post-immunization compared to COVID-19 naïve patients. Factors such as age, immunosuppressive regimen, eGFR, time since transplantation also impact vaccination response. This study aims to investigate COVID-19 infection outcome and vaccination response among KTRs during the Omicron surge. Method This study is a retrospective single-center cohort study at the Department of Nephrology and Transplantation at Skåne University Hospital in Malmö, Sweden. KTRs infected with COVID-19 during the Omicron surge were included (January 2022 until August 2023). Results 97 KTRs diagnosed with COVID-19 were included of whom 91 were vaccinated. In average, three doses of COVID-19-vaccine had been given to the patients. 67 KTRs showed seroconversion, 28 remained seronegative and the status of the remaining 2 KTRs was unknown. There was a significant association between lack of antibody production and mycophenolic acid (MPA) treatment (P = 0.019, Chi2 test), however the significance was not retained in a multivariate logistic regression analysis. Among the seroconverted (n = 67), 61 experienced mild infection, 5 moderate infection and 1 severe infection, according to the WHO clinical progression scale. In the seronegative group (n = 28), 25 had mild infection while the remaining three had moderate infection. The median time for viral clearance was examined in 79 KTRs and was 23 days (IQR 18-31). Immunosuppression was adjusted in 34% (n = 33) of cases. 2.1% (n = 2) of KTRs experienced graft rejection post infection. Conclusion While most patients experienced a mild infection, unlike during the first surges of the pandemic, the observed subsequent graft rejections emphasize the complexity of COVID-19´s potentially immunologic triggering effect and risk of graft loss in KTRs. The correlation between MPA treatment and a lower degree of serologic conversion after vaccination underscores the need for personalized immunologic follow up and treatment regimen in KTRs.