de Vries, Aiko P J

ABSTRACTIntroductionThe diagnosis of antibody‐mediated rejection (AMR) requires input from several transplant professionals. Bringing clinical and laboratory experts together may help standardize care. Yet, little is known about current global practices of multidisciplinary meetings for AMR management.MethodsThe Banff Antibody‐Mediated Injury Working Group approached professional societies worldwide to distribute a survey on the availability, content, participants, perceived value, and barriers to the implementation of multidisciplinary meetings.ResultsFour hundred two transplant professionals from six continents caring for kidney (90.55%), liver (21.14%), pancreas (20.65%), heart (15.17%), and lung (14.18%) transplant recipients participated in the survey, and 302 (75.12%) reported attending multidisciplinary meetings. Multidisciplinary meetings were more prevalent in academic centers, in high‐ versus low‐to‐middle‐income regions (81.03% and 65.99%, respectively; p < 0.001), and in mid‐to‐large size transplant programs compared to smaller programs. Perceived value included continued professional development (97.68%) and trainee education (95.70%). AMR was reported to be discussed at these meetings by 217 respondents with case presentations reviewing patient characteristics, histology, and HLA antibody data. A third of the respondents reviewed non‐HLA/pathogenic autoantibodies and/or molecular diagnostics, with the latter being more frequently applied in high‐ versus low‐to‐middle‐income regions (46.71% and 12.31%, respectively; p < 0.001). AMR case presentations allowed diagnosis revision, actionable management plans and were perceived as improving care. The primary barrier to the implementation of multidisciplinary meetings (63.27%) was the unavailability of transplant professionals (e.g., transplant immunologists).ConclusionFacilitating multidisciplinary meetings through the remote participation of pertinent experts and incentivizing participation through remuneration, protected time, or continued medical education may help standardize AMR diagnosis and harmonize its management.

In September 2022, in Banff, Alberta, Canada, the XVIth Banff meeting, corresponding to the 30th anniversary of the Banff classification, was held, leading to 2 recent publications. Discussions at the Banff meeting focused on proposing improvements to the Banff process as a whole. In line with this, a unique opportunity was offered to a selected group of 16 representatives from the pathology and transplant nephrology community, experts in the field of kidney transplantation, to review these 2 Banff manuscripts. The aim was to provide an insightful commentary, to gauge any prospective influence the proposed changes may have, and to identify any potential areas for future enhancement within the Banff classification. The group expressed its satisfaction with the incorporation of 2 new entities, namely “microvascular inflammation/injury donor-specific antibodies–negative and C4d negative” and “probable antibody-mediated rejection,” into category 2. These changes expand the classification, facilitating the capture of more biopsies and providing an opportunity to explore the clinical implications of these lesions further. However, we found that the Banff classification remains complex, potentially hindering its widespread utilization, even if a degree of complexity may be unavoidable given the intricate pathophysiology of kidney allograft pathology. Addressing the histomorphologic diagnosis of chronic active T cell–mediated rejection (CA TCMR), potentially reconsidering a diagnostic-agnostic approach, as for category 2, to inflammation in interstitial fibrosis and tubular atrophy and chronic active T cell–mediated rejection was also an important objective. Furthermore, we felt a need for more evidence before molecular diagnostics could be routinely integrated and emphasized the need for clinical and histologic context determination and the substantiation of its clinical impact through rigorous clinical trials. Finally, our discussions stressed the ongoing necessity for multidisciplinary decision-making regarding patient care.

ABSTRACT Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6–8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium ( n Stage1 : 111,666; n Stage2 : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea ( PPM1J , EDEM3, ACP1, SPEG, EYA4, CYP1A1 , and ATXN2L ; P Stage1 <3.7×10 −7 ), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 ( P =5.4×10 −8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2 -knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.