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

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

Surgical complications and technical failure of simultaneous pancreas-kidney transplantation: A 22-year experience from a single center.

Simultaneous pancreas-kidney transplantation (SPKT) is the best treatment for selected individuals with type 1 diabetes mellitus and end-stage renal disease. Despite advances in surgical techniques, donor and recipient selection, and immunosuppressive therapies, SPKT remains a complex procedure with associated surgical complications and adverse consequences. We conducted a retrospective study that included 263 SPKT procedures performed between May 2000, and December 2022. A total of 65 patients (25%) required at least one relaparotomy, resulting in an all-cause relaparotomy rate of 2.04 events per 100 in-hospital days. Lower donor body mass index was identified as an independent factor associated with reoperation (OR .815; 95% CI:  .725-.917, p = .001). Technical failure (TF) occurred in 9.9% of cases, primarily attributed to pancreas graft thrombosis, intra-abdominal infections, bleeding, and anastomotic leaks. Independent predictors of TF at 90 days included donor age above 36 years (HR 2.513; 95% CI 1.162-5.434), previous peritoneal dialysis (HR 2.503; 95% CI 1.149-5.451), and specific pancreas graft reinterventions. The findings highlight the importance of carefully considering donor and recipient factors in SPKT. The incidence of TF in our study population aligns with the recent series. Continuous efforts should focus on identifying and mitigating potential risk factors to enhance SPKT outcomes, thereby reducing post-transplant complications.

Hepatitis C viremic lung transplantation to aviremic recipients: Comprehensive outcomes and post-transplant viremia.

BACKGROUND/AIMS: Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). METHODS: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. RESULTS: We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p = .43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p = .89, p = .87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p = .90, p = .88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p = .3), acute cellular rejection (60.0% vs. 58.0%, p = .8) and antibody-mediated rejection (16.7% vs. 14.2%, p = .7). CONCLUSION: There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.

Induction therapy in heart transplantation: A systematic review and network meta-analysis for developing evidence-based recommendations.

INTRODUCTION: Induction therapy (IT) utility in heart transplantation (HT) remains contested. Commissioned by a clinical-practice guidelines panel to evaluate the effectiveness and safety of IT in adult HT patients, we conducted this systematic review and network meta-analysis (NMA). METHODS: We searched for studies from January 2000 to October 2022, reporting on the use of any IT agent in adult HT patients. Based on patient-important outcomes, we performed frequentist NMAs separately for RCTs and observational studies with adjusted analyses, and assessed the certainty of evidence using the GRADE framework. RESULTS: From 5156 publications identified, we included 7 RCTs and 12 observational studies, and report on two contemporarily-used IT agents-basiliximab and rATG. The RCTs provide only very low certainty evidence and was uninformative of the effect of the two agents versus no IT or one another. With low certainty in the evidence from observational studies, basiliximab may increase 30-day (OR 1.13; 95% CI 1.06-1.20) and 1-year (OR 1.11; 95% CI 1.02-1.22) mortality compared to no IT. With low certainty from observational studies, rATG may decrease 5-year cardiac allograft vasculopathy (OR .82; 95% CI .74-.90) compared to no IT, as well as 30-day (OR .85; 95% CI .80-.92), 1-year (OR .87; 95% CI .79-.96), and overall (HR .84; 95% CI .76-.93) mortality compared to basiliximab. CONCLUSION: With low and very low certainty in the synthetized evidence, these NMAs suggest possible superiority of rATG compared to basiliximab, but do not provide compelling evidence for the routine use of these agents in HT recipients.

Bridge-to-transplant temporary mechanical circulatory support and risk of allosensitization.

INTRODUCTION: Since the 2018 change in the US adult heart allocation policy, more patients are bridged-to-transplant on temporary mechanical circulatory support (tMCS). Previous studies indicate that durable left ventricular assist devices (LVAD) may lead to allosensitization. The goal of this study was to assess whether tMCS implantation is associated with changes in sensitization. METHODS: We included patients evaluated for heart transplants between 2015 and 2022 who had alloantibody measured before and after MCS implantation. Allosensitization was defined as development of new alloantibodies after tMCS implant. RESULTS: A total of 41 patients received tMCS before transplant. Nine (22.0%) patients developed alloantibodies following tMCS implantation: 3 (12.0%) in the intra-aortic balloon pump group (n = 25), 2 (28.6%) in the microaxial percutaneous LVAD group (n = 7), and 4 (44.4%) in the veno-arterial extra-corporeal membrane oxygenation group (n = 9)-p = .039. Sensitized patients were younger (44.7 ± 11.6 years vs. 54.3 ± 12.5 years, p = .044), were more likely to be sensitized at baseline - 3 of 9 (33.3%) compared to 2 out of 32 (6.3%) (p = .028) and received more transfusions with red blood cells (6 (66.6%) vs. 8 (25%), p = .02) and platelets (6 (66.6%) vs. 5 (15.6%), p = .002). There was no significant difference in tMCS median duration of support (4 [3,15] days vs. 8.5 [5,14.5] days, p = .57). Importantly, out of the 11 patients who received a durable LVAD after tMCS, 5 (45.5%) became sensitized, compared to 4 out of 30 patients (13.3%) who only had tMCS-p = .028. CONCLUSIONS: Our findings suggest that patients bridged-to-transplant with tMCS, without significant blood product transfusions and a subsequent durable LVAD implant, have a low risk of allosensitization. Further studies are needed to confirm our findings and determine whether risk of sensitization varies by type of tMCS and duration of support.

Kidney transplant candidates' perspectives on the implementation of a Canadian Willingness to Cross program: A strategy to increase access to kidney transplantation for highly sensitized patients.

BACKGROUND: Kidney transplantation is the optimal treatment for end-stage renal disease. However, highly sensitized patients (HSPs) have reduced access to transplantation, leading to increased morbidity and mortality on the waiting list. The Canadian Willingness to Cross (WTC) program proposes allowing transplantation across preformed donor specific antibodies (DSA) determined to be at a low risk of rejection under the adaptive design framework. This study collected patients' perspectives on the development of this program. METHODS: Forty-one individual interviews were conducted with kidney transplant candidates from three Canadian transplant centers in 2022. The interviews were digitally recorded and transcribed for subsequent analyses. RESULTS: Despite limited familiarity with the adaptive design, participants demonstrated trust in the researchers. They perceived the WTC program as a pathway for HSPs to access transplantation while mitigating transplant-related risks. HSPs saw the WTC program as a source of hope and an opportunity to leave dialysis, despite acknowledging inherent uncertainties. Some non-HSPs expressed concerns about fairness, anticipating increased waiting times and potential compromise in kidney graft longevity due to higher rejection risks. Participants recommended essential strategies for implementing the WTC program, including organizing informational meetings and highlighting the necessity for psychosocial support. CONCLUSION: The WTC program emerges as a promising strategy to enhance HSPs' access to kidney transplantation. While HSPs perceived this program as a source of hope, non-HSPs voiced concerns about distributive justice issues. These results will help develop a WTC program that is ethically sound for transplant candidates.

Donor heart dysfunction and graft survival in liver and kidney transplants-A register-based study from Sweden.

BACKGROUND AND AIM: Stress cardiomyopathy in donors can potentially affect graft function and longevity. This study aims to investigate the association between echocardiographic left ventricular ejection fraction (LVEF) < 50%, and/or the presence of left ventricular regional wall motion abnormalities (RWMA) in organ donors, and short- and long-term liver and kidney graft survival. Our secondary aim was to link graft survival with donor and recipient characteristics. METHODS: All donors considered for liver and kidney donation with echocardiographic records at Sahlgrenska University Hospital between 2006 and 2016 were matched with their recipients through the Scandiatransplant register. The studied outcomes were graft survival, re-transplantation, and recipient death. Kaplan-Meier curves were used to plot time to event. Multivariate Cox-regression was used to test independence. RESULTS: There were 370 liver donors and 312 kidney donors (matched with 458 recipients) with echocardiographic records at Sahlgrenska University Hospital between June 2006 and November 2016. Of patients with LV dysfunction by echocardiography, there were 102 liver- and 72 kidney donors. Univariate survival analyses showed no statistical difference in the short- and long-term graft survival from donors with LV dysfunction compared to donors without. Donor age > 65 years, recipient re-transplantation and recipient liver tumor were predictors of worse outcome in liver transplants (p < .05). Donor age > 65, donor hypertension, recipient re-transplantation, and a recipient diagnosis of diabetes or nephritis/glomerulonephritis had a negative association with graft survival in kidney transplants (p < .05). CONCLUSION: We found no significant association between donor LV dysfunction and short- and long-term graft survival in liver and kidney transplants, suggesting that livers and kidneys from such donors can be safely transplanted.

Risk factors for Pneumocystis jirovecii pneumonia after kidney transplantation: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection, often leads to an increase in hospitalization time and mortality rates in kidney transplant (KT) recipients. However, the risk factors associated with PJP in KT recipients remain debatable. Therefore, we conducted this meta-analysis to identify risk factors for PJP, which could potentially help to reduce PJP incidence and improve outcome of KT recipients. METHODS: We systematically retrieved relevant studies in PubMed, EMBASE, and the Cochrane Library up to November 2023. Pooled odds ratios (ORs) or mean differences (MDs) and the corresponding 95% confidence intervals (CIs) were calculated to assess the impact of potential risk factors on the occurrence of PJP. RESULTS: 27 studies including 42383 KT recipients were included. In this meta-analysis, age at transplantation (MD = 3.48; 95% CI = .56-6.41; p = .02), cytomegalovirus (CMV) infection (OR = 4.00; 95% CI = 2.53-6.32; p = .001), BK viremia (OR = 3.38; 95% CI = 1.70-6.71; p = .001), acute rejection (OR = 3.66; 95% CI = 2.44-5.49; p = .001), ABO-incompatibility (OR = 2.51; 95% CI = 1.57-4.01; p = .001), estimated glomerular filtration rate (eGFR) (MD = -14.52; 95% CI = -25.37- (-3.67); p = .009), lymphocyte count (MD = -.54; 95% CI = -.92- (-.16); p = .006) and anti-PJP prophylaxis (OR = .53; 95% CI = .28-.98; p = .04) were significantly associated with PJP occurrence. CONCLUSION: Our findings suggest that transplantation age greater than 50 years old, CMV infection, BK viremia, acute rejection, ABO-incompatibility, decreased eGFR and lymphopenia were risk factors for PJP.

A heart transplant center experience with basiliximab induction strategies: A double edged sword?

BACKGROUND: The use of induction immunosuppression for heart transplantation (HT) is debated given the uncertain benefit and potential risks of infection and malignancy. METHODS: This is a retrospective single-center analysis of 475 consecutive HT recipients from 2003 to 2020 grouped by use of induction with basiliximab group (BG) and the no basiliximab group (NBG). Subgroup analysis by era compared pre-2016 standard-basiliximab (BX) induction and 2016-2020 with selective-BX use as part of a calcineurin-inhibitor-sparing regimen. RESULTS: When adjusted for confounders (sex, age, PRA, eGFR), the BG was less likely to have acute cellular rejection (ACR) (OR.42, p < .001), but had more antibody mediated rejection (AMR) (OR 11.7, p < .001) and more cardiac allograft vasculopathy (CAV) (OR 3.8, p = .04). There was no difference between BG and NBG in the incidence of malignancies or infections. When stratified by era (pre-2016 vs. 2016-2020), ACR remained less common in the BG than the NBG (36% vs. 50%, p = .045) groups, while AMR remained more common (9.7 vs. 0% p = .005). There was no significant difference in conditional survival comparing pre-and post-2016 NBG (HR 2.20 (95% CI.75-6.43); however, both pre-2016 BG and post-2016 BG have significantly higher mortality (HR 2.37 [95% CI 1.02-5.50) and HR 2.69 (95% CI 1.08-6.71), p = .045 and.03, respectively]. CONCLUSION: Basiliximab reduces the incidence of ACR but increases the risk of AMR, CAV, and may be associated with increased mortality. Mechanistic studies are needed to describe a potential T-cell-escape mechanism with enhanced humoral immunity.

Extracellular vesicles as potential diagnostic markers for kidney allograft rejection.

Kidney transplantation is a highly effective treatment for end-stage kidney disease. However, allograft rejection remains a significant clinical challenge in kidney transplant patients. Although kidney allograft biopsy is the gold-standard diagnostic method, it is an invasive procedure. Since the current monitoring methods, including screening of serum creatinine and urinary protein, are not of sufficient sensitivity, there is a need for effective post-transplant monitoring to detect allograft rejection at an early stage. Extracellular vesicles are vesicles with a lipid bilayer that originate from different cell types in pathological and physiological conditions. The content of extracellular vesicles reflects the status of cells at the time of their production. This review comprehensively summarizes clinical, in vivo, and in vitro reports that highlight the potential of extracellular vesicles as diagnostic biomarkers for kidney allograft rejection. Clarification would facilitate differentiation between rejection and non-rejection and identification of the mechanisms involved in the allograft rejection. Despite increasing evidence, further research is necessary to establish the clinical utility of extracellular vesicles in the diagnosis and monitoring of allograft rejection in kidney transplant recipients. Using extracellular vesicles as non-invasive biomarkers for diagnosis of kidney allograft rejection could have tremendous benefits in improving patient outcomes and reduce the need for invasive procedures.

Recipient donor sex combinations in solid organ transplantation and impact on clinical outcome: A scoping review.

INTRODUCTION: Solid organ transplantation (SOT) is a lifesaving treatment for end-stage organ failure. Although many factors affect the success of organ transplantation, recipient and donor sex are important biological factors influencing transplant outcome. However, the impact of the four possible recipient and donor sex combinations (RDSC) on transplant outcome remains largely unclear. METHODS: A scoping review was carried out focusing on studies examining the association between RDSC and outcomes (mortality, graft rejection, and infection) after heart, lung, liver, and kidney transplantation. All studies up to February 2023 were included. RESULTS: Multiple studies published between 1998 and 2022 show that RDSC is an important factor affecting the outcome after organ transplantation. Male recipients of SOT have a higher risk of mortality and graft failure than female recipients. Differences regarding the causes of death are observed. Female recipients on the other hand are more susceptible to infections after SOT. CONCLUSION: Differences in underlying illnesses as well as age, immunosuppressive therapy and underlying biological mechanisms among male and female SOT recipients affect the post-transplant outcome. However, the precise mechanisms influencing the interaction between RDSC and post-transplant outcome remain largely unclear. A better understanding of how to identify and modulate these factors may improve outcome, which is particularly important in light of the worldwide organ shortage. An analysis for differences of etiology and causes of graft loss or mortality, respectively, is warranted across the RDSC groups. PRACTITIONER POINTS: Recipient and donor sex combinations affect outcome after solid organ transplantation. While female recipients are more susceptible to infections after solid organ transplantation, they have higher overall survival following SOT, with causes of death differing from male recipients. Sex-differences should be taken into account in the post-transplant management.

Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Impact of delayed listing after initiating kidney transplant evaluation on transplant outcomes.

OBJECTIVE: Longer end-stage renal disease time has been associated with inferior kidney transplant outcomes. However, the contribution of transplant evaluation is uncertain. We explored the relationship between time from evaluation to listing (ELT) and transplant outcomes. METHODS: This retrospective study included 2535 adult kidney transplants from 2000 to 2015. Kaplan-Meier survival curves, log-rank tests, and Cox regression models were used to compare transplant outcomes. RESULTS: Patient survival for both deceased donor (DD) recipients (p < .001) and living donor (LD) recipients (p < .0001) was significantly higher when ELT was less than 3 months. The risks of ELT appeared to be mediated by other risks in DD recipients, as adjusted models showed no associated risk of graft loss or death in DD recipients. For LD recipients, ELT remained a risk factor for patient death after covariate adjustment. Each month of ELT was associated with an increased risk of death (HR = 1.021, p = .04) but not graft loss in LD recipients in adjusted models. CONCLUSIONS: Kidney transplant recipients with longer ELT times had higher rates of death after transplant, and ELT was independently associated with an increased risk of death for LD recipients. Investigations on the impact of pretransplant evaluation on post-transplant outcomes can inform transplant policy and practice.

Real-life use of letermovir prophylaxis for cytomegalovirus in heart transplant recipients.

INTRODUCTION: Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high-risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR). METHODS: In this observational, retrospective, single-center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen. RESULTS: The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor-positive, recipient-negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3-12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir. CONCLUSION: This real-life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post-treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted.

The role of anticomplement therapy in the management of the kidney allograft.

As the number of patients living with kidney failure grows, the need also grows for kidney transplantation, the gold standard kidney replacement therapy that provides a survival advantage. This may result in an increased rate of transplantation from HLA-mismatched donors that increases the rate of antibody-mediated rejection (AMR), which already is the leading cause of allograft failure. Plasmapheresis, intravenous immunoglobulin therapy, anti-CD20 therapies (i.e., rituximab), bortezomib and splenectomy have been used over the years to treat AMR as well as to prevent AMR in high-risk sensitized kidney transplant recipients. Eculizumab and ravulizumab are monoclonal antibodies targeting the C5 protein of the complement pathway and part of the expanding field of anticomplement therapies, which is not limited to kidney transplant recipients, and also includes complement-mediated microangiopathic hemolytic anemia, paroxysmal nocturnal hemoglobinuria, and ANCA-vasculitis. In this narrative review, we summarize the current knowledge concerning the pathophysiological background and use of anti-C5 strategies (eculizumab and ravulizumab) and C1-esterase inhibitor in AMR, either to prevent AMR in high-risk desensitized patients or to treat AMR as first-line or rescue therapy and also to treat de novo thrombotic microangiopathy in kidney transplant recipients.

Protocol liver biopsy predicts graft survival after liver transplantation.

BACKGROUND: The use of protocol liver biopsy to monitor liver allograft status remains controversial. There is limited data from modern transplantation populations that includes protocol biopsies to evaluate its value in predicting clinical outcomes. METHODS: All protocol liver biopsies were identified from 875 patients who underwent liver transplantation at Helsinki University Hospital between 2000 and 2019. Each histologic component was analyzed for its ability to predict long-term outcomes, especially graft survival. We determined the frequency of significant biopsy findings based on the Banff working group definition. Liver function tests (LFTs) and clinical markers were evaluated for their ability to predict significant biopsy findings. RESULTS: In total, 867 protocol liver biopsies were analyzed. Significant findings were identified in 20.1% of the biopsies. In the first protocol biopsy, steatohepatitis (hazard ratio [HR] 3.504, p = .03) and moderate or severe congestion (HR 3.338, p = .04) predicted graft loss. The presence of cholangitis (HR 2.563, p = .04), necrosis (HR 7.635, p < .001), mild congestion (HR 4.291, p = .009), and significant biopsy finding (HR 2.540, p = .02) predicted inferior death-censored graft survival. While the degree of elevation of LFTs was positively associated with significant biopsy findings, the discrimination was poor (AUC .572-.622). Combined LFTs and clinical risk factors remained suboptimal for discriminating significant biopsy findings (AUC .696). CONCLUSIONS: Our findings support the use of protocol liver biopsies after liver transplantation since they frequently revealed changes associated with long-term outcomes, even when LFTs were normal.

Routine screening for HLA Antibodies in Heart Transplant patients-Does it affect clinical decision making?

BACKGROUND: We aimed to assess outcomes in patients with and without donor specific antibodies (DSA) and to evaluate the relationship between DSA presence and graft function, cardiac allograft vasculopathy (CAV), and mortality. METHODS: The study population comprises 193 consecutive long-term heart transplanted (HTx) patients who underwent DSA surveillance between 2016 and 2022. The patients were prospectively screened for CAV through serial coronary angiograms, graft function impairment through serial echocardiograms, and cardiac biomarkers. The patients were followed from the first DSA measurement until death, 5 years follow-up or right censuring on the 30th of June 2023. RESULTS: DSAs were detected in 50 patients using a cut-off at MFI ≥1000 and 45 patients using a cut-off at ≥2000 MFI. The median time since HTx was 9.0 years [3.0-14.4]. DSA positive patients had poorer graft function and higher values of NT-proBNP and troponin T, and more prevalent CAV than DSA negative patients. In total, 25 patients underwent endomyocardial biopsies due to DSA presence while another eight patients underwent endomyocardial biopsies for other reasons. Histological antibody mediated rejection (AMR) signs were seen in three biopsies. During a median follow-up of five years [4.7-5], a total of 41 patients died. Mortality rates did not differ between DSA positive and DSA negative patients (HR 1.2, 95% CI .6-2.4). DSA positive patients were more likely to experience CAV progression than DSA negative patients (HR 2.7, 95% CI 1.5-4.8) CONCLUSIONS: Routine screening reveals DSA in approximately 25% of long-term HTx patients but is rarely related to histopathological AMR signs. DSA presence was associated with poorer graft function and more prevalent and progressive CAV. However, DSA positive patients had similar survival rates to DSA negative patients.

Utility of a fusion protein T-cell co-stimulation blocker Belatacept in heart transplant recipients: Real world experience from a high volume center.

BACKGROUND: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. RESULTS: Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). CONCLUSION: In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.