Search

Non-invasive biomarkers are promising tools for improving kidney allograft rejection monitoring, but their clinical adoption requires more evidence in specifically designed studies. To address this unmet need, we designed the EU-TRAIN study, a large prospective multicentric unselected cohort funded by the European Commission. Here, we included consecutive adult patients who received a kidney allograft in nine European transplant centers between November 2018 and June 2020. We prospectively assessed gene expression levels of 19 blood messenger RNAs, four antibodies targeting non-human leukocyte antigen (HLA) endothelial antigens, together with circulating anti-HLA donor-specific antibodies (DSA). The primary outcome was allograft rejection (antibody-mediated, T cell-mediated, or mixed) in the first year post-transplantation. Overall, 412 patients were included, with 812 biopsies paired with a blood sample. CD4 gene expression was significantly associated with rejection, while circulating anti-HLA DSA had a significant association with allograft rejection and a strong association with antibody-mediated rejection. All other tested biomarkers, including AKR1C3, CD3E, CD40, CD8A, CD9, CTLA4, ENTPD1, FOXP3, GZMB, ID3, IL7R, MS4A1, MZB1, POU2AF1, POU2F1, TCL1A, TLR4, and TRIB1, as well as antibodies against angiotensin II type 1 receptor, endothelin 1 type A receptor, C3a and C5a receptors, did not show significant associations with allograft rejection. The blood messenger RNAs and non-HLA antibodies did not show an additional value beyond standard of care monitoring parameters and circulating anti-HLA DSA to predict allograft rejection in the first year post-transplantation. Thus, our results open avenues for specifically designed studies to demonstrate the clinical relevance and implementation of other candidate non-invasive biomarkers in kidney transplantation practice., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) has a high prevalence in Cameroon and will become an important public health problem. Its management must be comprehensive, starting with CKD prevention to the implementation of renal replacement therapies best suited to the needs of patients and resources available in Cameroon. Practical interventions involving nephrology departments in both Africa and Europe can contribute to an improved management of CKD in Africa. The current collaboration between the Geneva University Hospitals and the Yaoundé teaching hospitals is a convincing example. It includes a clinical trial on the treatment of metabolic acidosis linked to CKD, assistance with the placement of hemodialysis catheters by sonography and the initiation of a kidney transplantation program with living donors., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Allogeneic islet transplantation is a standard of care treatment for patients with labile type 1 diabetes in many countries around the world, including Japan, the United Kingdom, Australia, much of continental Europe, and parts of Canada. The United States is now endorsing islet cell treatment for type 1 diabetes, but the FDA has chosen to consider islets as a biologic that requires licensure, making the universal implementation of the procedure in the clinic very challenging and opening the manufacture of islet grafts to private companies. The commercialization of human tissues raises significant legal and ethical issues and ironically leads to a situation where treatments developed as a result of the scientific and economic efforts of academia over several decades become exploited exclusively by for-profit entities., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: Europe is currently the most active region in the field of pancreatic islet transplantation, and many of the leading groups are actually achieving similar good outcomes. Further collaborative advances in the field require the standardization of islet cell product isolation processes, and this work aimed to identify differences in the human pancreatic islet isolation processes within European countries., Methods: A web-based questionnaire about critical steps, including donor selection, pancreas processing, pancreas perfusion and digestion, islet counting and culture, islet quality evaluation, microbiological evaluation, and release criteria of the product, was completed by isolation facilities participating at the Ninth International European Pancreas and Islet Transplant Association (EPITA) Workshop on Islet-Beta Cell Replacement in Milan., Results: Eleven islet isolation facilities completed the questionnaire. The facilities reported 445 and 53 islet isolations per year over the last 3 years from deceased organ donors and pancreatectomized patients, respectively. This activity resulted in 120 and 40 infusions per year in allograft and autograft recipients, respectively. Differences among facilities emerged in donor selection (age, cold ischemia time, intensive care unit length, amylase concentration), pancreas procurement, isolation procedures (brand and concentration of collagenase, additive, maximum acceptable digestion time), quality evaluation, and release criteria for transplantation (glucose-stimulated insulin secretion tests, islet numbers, and purity). Moreover, even when a high concordance about the relevance of one parameter was evident, thresholds for the acceptance were different among facilities., Conclusions: The result highlighted the presence of a heterogeneity in the islet cell product process and product release criteria.

Objective: To evaluate the European experience after Adult-to-adult living donor liver transplantation using the left liver (LL-aLDLT)., Summary Background Data: LL-aLDLT decreases donor risk but provides a smaller graft that increases recipient risk as compared with right liver (RL-aLDLT). However, there is little knowledge of results obtained after LL-aLDLT in Europe., Methods: This is a European multicenter retrospective study which aims to analyze donor and recipient outcomes after 46 LL-aLDLT., Results: Seventy-six percent of the grafts were harvested by minimally invasive approach. Mean donor hospital stay was 7.5 ± 3.5 days. Donor liver function was minimally impaired, with 36 donors (78.3%) without any 90-day complication, and 4 (8.7%) presenting major complications. One, 3, and 5-year recipient survival was 90.9%, 82.7%, and 82.7%, respectively. However, graft survival was of 59.4%, 56.9%, and 56.9% at 1, 3, and 5 years respectively, due to a 26.1% urgent liver retransplantation (ReLT) rate, mainly due to SFSS (n = 5) and hepatic artery thrombosis (HAT, n = 5). Risk factor analysis for ReLT and HAT showed an association with a graft to body weight ratio (GBWR) <0.6% (P = 0.01 and P = 0.024, respectively) while SFSS was associated with a recipient MELD ≥14 (P = 0.019). A combination of donor age <45 years, MELD <14 and actual GBWR >0.6% was associated with a lower ReLT rate (0% vs. 33%, P = 0.044)., Conclusions: Our analysis showed low donor morbidity and preserved liver function. Recipient outcomes, however, were hampered by a high ReLT rate. A strict selection of both donor and recipients is the key to minimize graft loss.

Defined outcomes for beta cell replacement therapy in the treatment of diabetes are critically needed. Progress towards the clinical acceptance of pancreas and islet transplantation has been hampered by the lack of clear definitions of functional and efficacy outcomes, as well as a lack of consistently applied glycaemic control metrics, together with poor alignment with the field of artificial insulin delivery/artificial pancreas development. To address this problem, the International Pancreas & Islet Transplant Association (IPITA) collaborated with the European Pancreas and Islet Transplant Association (EPITA) to develop a consensus for a joint statement on the definition of function and failure of beta cell replacement therapies, which is summarised in this commentary.

The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.

Background: Simultaneous pancreas-kidney (SPK) transplantation has become the therapy of choice for type 1 diabetic patients with end-stage renal disease. The current analysis examined the impact of human leukocyte antigen (HLA) matching on graft outcome following SPK transplantation. The study population was obtained from patients enrolled in the Euro-SPK 001 study., Methods: The effect of HLA matching on graft function and survival was assessed in 180 SPK recipients in whom complete donor-recipient HLA data were available. A group of 45 patients with 0-3 HLA mismatches (MM) was compared with a group of 135 patients with 4-6 MM., Results: There were no differences in 3-year kidney, pancreas or patient survival between the 0-3 and 4-6 MM groups. Biological parameters of kidney and pancreas graft function were similar in both groups. Significantly more patients with 0-3 MM (66%) were rejection-free at 3 years than was the case among those with 4-6 MM (41%; P = 0.003). The relative risk of acute rejection was 2.6 times higher among patients with 4-6 MM than among those with 0-3 MM., Conclusions: There was no evidence that HLA matching was associated with improved kidney or pancreas survival. However, a higher rate of acute rejection was observed with poor HLA match, which may impact long-term survival.

Background: Simultaneous pancreas-kidney transplantation (SPK) transplantation has become an accepted therapy for type 1 diabetic patients with end-stage renal disease. This open-label, multicenter study compared the efficacy and safety of tacrolimus with the microemulsion (ME) formulation of cyclosporine in a clinical setting. The 1-year results are reported here., Methods: The study was conducted in 10 European centers and one center in Israel. One hundred three patients were randomly assigned to tacrolimus and 102 to cyclosporine-ME. All patients received concomitant rabbit anti-T-cell globulin induction therapy, mycophenolate mofetil (MMF), and short-term cortico-steroids. The initial daily oral doses were 0.2 mg/kg for tacrolimus, 7 mg/kg for cyclosporine-ME, and 2 to 3 g for MMF., Results: The 1-year incidence of biopsy-proven kidney or pancreas acute rejection was lower with tacrolimus (27.2%) than with cyclosporine-ME (38.2%; P = 0.09). Pancreas graft survival at 1 year was 91.3% with tacrolimus and 74.5% with cyclosporine-ME (P <0.0005). Renal graft survival was similar in the two study groups. There were no significant treatment-related differences in pancreatic or renal graft function. In total, 34 patients switched treatment from cyclosporine-ME to tacrolimus, but only 6 patients receiving tacrolimus required alternative therapy. Mean doses of MMF at 1 year were also lower in the tacrolimus group (1.36 vs. 1.67 g/day; P = 0.007)., Conclusion: These findings support the use of tacrolimus therapy for uremic patients with type 1 diabetes who are undergoing SPK transplantation.