Transplant International最新文献

The management of immunosuppression in dialysis patients with a failed kidney transplant remains a pending question, and different approaches to immunosuppression weaning have been proposed. We conducted a retrospective study of patients who experienced a graft failure, and compared the rates of immune and non-immune events, according to different modalities of immunosuppression withdrawal. Two hundred and eighteen patients were included. During the follow-up (45 (20-80) months post-graft failure), 53 patients (24.3%) experienced an intolerance syndrome. The time between graft failure and the occurrence of intolerance syndrome was 6 (3-13) months. Immunosuppression withdrawal was associated with the occurrence of intolerance syndrome. However, regarding the immunosuppression withdrawal modality, only a steroid cessation during the first 3 months post graft failure was independently associated with an earlier occurrence of intolerance syndrome [HR = 1.91, 95%CI (1.08-3.38), p = 0.025], while a longer time between transplantation to graft failure was independently associated with a delayed occurrence of intolerance syndrome [HR = 0.99, 95%CI (0.98-0.99), p = 0.009]. The immunosuppression withdrawal modality after graft failure didn't have an impact on infections and cardiovascular complications. Although discontinuation of immunosuppression strongly influences the occurrence of intolerance syndrome, immunosuppression withdrawal modality itself does not appear to.

Maribavir is indicated for the treatment of refractory cytomegalovirus (CMV) infection/disease in patients who have undergone a solid organ transplant (SOT) or hematopoietic cell transplant (HCT). Only limited data on its use in real-world settings have been published from retrospective series. This retrospective study describes the real-world effectiveness of maribavir in 79 transplant patients with refractory CMV infection (67 SOT and 12 HCT) treated under a compassionate use program in France between October 2021 and April 2023. Maribavir was administered for <8 weeks, 8 weeks, and >8 weeks in 17, 32, and 30 patients, respectively. The response rate, defined as viremia clearance, was 53.2%, with a median time to first CMV clearance of 59 days. CMV clearance was observed in patients beyond 8 weeks of treatment. De novo maribavir resistance mutations were observed in 13.9% of patients, and CMV recurrence occurred in 45.2% of patients. Presence of CMV disease at baseline was associated with a lower likelihood of maribavir response. Compared to the pivotal SOLSTICE trial, real-world maribavir use demonstrated comparable effectiveness and a lower emergence of maribavir resistance. Moreover, outcomes of patients with a longer treatment duration suggested potential benefits of extending maribavir therapy beyond the recommended 8 weeks.

Institut Georges Lopez-2M (IGL-2M), a novel preservation solution containing polyethylene glycol (PEG 35kD, 5 g/L), preserves mitochondrial integrity and redox balance in liver grafts. This study assesses IGL-2M's effect on lung preservation during prolonged cold ischemia. Rat's heart-lung blocks were procured and subjected to 18 h cold ischemia (4 °C). Lungs were flushed and preserved using one of these preservation solutions: OCS, Perfadex Plus, IGL-2M (n = 6/group). Following ischemia, lungs underwent up to 7 h normothermic ex vivo lung perfusion. Edema was quantified by weight gain. Lung physiological parameters were recorded. Perfusate, bronchoalveolar lavage (BAL), and tissue samples were collected. All lungs in IGL-2M group completed 7 h EVLP protocol. Compared to OCS, IGL-2M reduced edema formation (p < 0.01), preserved superior compliance (p < 0.01), and maintained lower pulmonary vascular resistance (p < 0.01). IGL-2M showed lower perfusate concentrations of IL-1β (p < 0.05), IL-6 (p < 0.05), and TNF-α (p = 0.08). In BAL, IGL-2M reduced IL-1β (p < 0.01), IL-6 (p < 0.05), TNF-α (p < 0.01), and CXCL1 (p < 0.01). IGL-2M showed lower release of Syndecan-1 (p < 0.05). Compared to Perfadex Plus, IGL-2M was not inferior, with reduced expression of TNF-α in the perfusate (p < 0.05). IGL-2M effectively prevents edema development like Perfadex Plus. IGL-2M results in decreased inflammation and a stronger endothelial lining, making it a promising solution for lung preservation.

In living donor liver transplantation (LDLT), large splenorenal shunts (SRS) can divert portal inflow and negatively affect graft function due to portal steal syndrome. Direct SRS ligation (SRSL) and left renal vein ligation (LRVL) are used to prevent this complication; however, the long-term renal impact of LRVL remains unclear, particularly in recipients requiring nephrotoxic immunosuppression. We retrospectively analyzed adult LDLT recipients with large SRS (>1 cm) and normal baseline renal function who underwent SRSL (n = 120) or LRVL (n = 74). Patient and graft survival, serial renal function profiles, and tacrolimus trough levels were evaluated. Survival outcomes were comparable between the two groups. LRVL was more frequently performed in patients with higher preoperative Model for End-Stage Liver Disease (MELD) scores or increased transfusion requirements. During long-term follow-up, the LRVL group showed a more evident decline in renal function, with persistently higher serum creatinine levels, despite similar tacrolimus exposure. Four recipients in the LRVL group progressed to end-stage renal disease requiring dialysis within 10 years, whereas no dialysis cases occurred following SRSL. Although both strategies are clinically feasible, LRVL demonstrated a stronger association with progressive renal deterioration. These findings suggest that SRSL may be preferred in recipients with renal vulnerability to minimize cumulative renal burden.

Despite the metabolic risks associated with corticosteroids after liver transplantation (LT), the optimal timing for their withdrawal remains uncertain due to limited and inconsistent evidence. To evaluate the impact of corticosteroid withdrawal timing on the development of de-novo post-transplant diabetes mellitus (PTDM), we performed a retrospective cohort study of 6,295 adult recipients who underwent LT between 2009 and 2021 in South Korea, utilizing a national health insurance claims database. A landmark analysis with time-varying propensity score matching was conducted at one-, three-, and six-month post-transplantation to compare the incidence of PTDM between steroid withdrawal and maintenance groups. Early steroid withdrawal within 3 months significantly reduced PTDM risk (HR = 0.586; 95% CI = 0.407-0.846 at 1 month, HR = 0.766; 95% CI = 0.611-0.960 at 3 month), whereas withdrawal after 3 months showed no significant benefit (HR = 0.844; 95% CI = 0.619-1.152 at 6 month). Rejection events were rare, suggesting no substantial compromise in graft function. These findings indicate that corticosteroid withdrawal within the first three months post-LT can lower the risk of PTDM without increasing rejection risk, supporting timely steroid tapering as part of post-transplant immunosuppressive strategies to reduce long-term metabolic complications.

Post-transplant lymphoproliferative disorder (PTLD) is a major complication of solid organ transplantation (SOT), with the greatest risk in Epstein-Barr virus (EBV) donor-positive/recipient-negative (D+/R-) pairs. The contribution of cytomegalovirus (CMV) serostatus is less well defined. We conducted a population-based study of 47,333 abdominal SOT recipients in the United States (1995-2015) using linked SRTR data. Donor-recipient EBV/CMV serostatus was evaluated as a compound variable. The primary outcome was PTLD incidence, with secondary analyses assessing predictors of PTLD and impact on survival. Overall, 716 patients (1.5%) developed PTLD at a median of 6.1 years (IQR 2.9-9.7) after transplant. EBV D+/R- recipients had the highest incidence (3.2%), and those with compound [EBV D+/R-, CMV D-/R-] serostatus had more than double the PTLD risk compared with [EBV D+/R-, CMV D+/R-] (5.3% vs. 2.5%, p < 0.001). Logistic regression and random forest models consistently identified [EBV D+/R-, CMV D-/R-] serostatus, age, and race as leading predictors, though discrimination was modest (test AUC ∼0.61). In a matched survival analysis, PTLD was not associated with increased all-cause mortality (aHR ∼1.0). Our findings demonstrate that combined EBV/CMV serostatus improves PTLD risk prediction compared with EBV alone and emphasize the need for targeted preventive strategies.

Glomerular filtration rate (GFR) is a crucial parameter in post-transplant follow-up (PTF). CKD-EPI 2009 creatinine-based equation remains the most used estimated GFR (eGFR) and only few data are available on the other equations, based on creatinine, cystatin C or their combination. We evaluated 10 GFR estimation equations on 242 kidney-transplant recipient patients having measured GFR (mGFR) determination (urinary clearance of ^99mTc-DTPA) with simultaneous plasma enzymatic creatinine and serum cystatin C (immunoturbidimetry or immunonephelemetry) assessments. Five creatinine (MDRD 2006, CKD-EPI 2009 and 2021, EKFC 2021, KRS 2023), two cystatin C (CKD-EPI 2012, EKFC 2023) and three combined eGFR (CKD-EPI 2012 and 2021, combined EKFC) were evaluated. All equations were significantly correlated with mGFR (R² = 0.672-0.745) with a low median bias (+4.2 to -1.1 mL/min/1.73 m²). Chronic kidney disease staging agreements were all above 68% (maximum: 79.3% for CKD-EPI comb 2021). Percentages of eGFR comprised in between 30% of the mGFR ranged from 85.5% to 87.6% (combined equations), from 83.1% to 84.3% (cystatin C equations) and from 75.2% to 81.4% (creatinine equations). Combined creatinine/cystatin C eGFR equations with a P30 value greater to 85% of transplant recipients appeared closer to mGFR than cystatin C or creatinine eGFR.

Lung transplantation (LTx) offers life-saving therapy for patients with end-stage lung disease but remains limited by donor shortages, complex postoperative management and graft failure. Machine learning (ML) enables opportunities to address these challenges by identifying patterns in complex, high-dimensional data, thereby providing novel insights and improving outcomes. This review outlines ML studies in LTx and explains the methodologies. ML has demonstrated promising results in organ allocation and outcome prediction. Techniques such as support vector machines, and deep learning are useful in risk stratification, while methods like random forests improve interpretability and transfer learning supports model development in data-scarce settings. ML has a growing role in multi-omics data and imaging-based diagnostics. Despite promising results, barriers such as small datasets, cross-center inconsistency, poor interpretability, and limited external validation, hinder clinical adoption. Future progress requires multicenter collaborations, transparent methodologies, and integration within clinical workflows. ML should serve as complementary tool that enhances decision-making, rather than replacing clinical judgement. With careful implementation, it holds the potential to improve transplant outcomes.

[This corrects the article DOI: 10.3389/ti.2025.15061.].