#276 ADTKD genetic diagnostics in Europe: where do we stand and what is needed?

Abstract

Abstract Background and Aims We are the first European patient organization to pursue the goal of raising awareness of the monogenic kidney disease ADTKD (autosomal dominant tubulointerstitial kidney disease) and supporting its research (www.adtkd.de/en-gb). To date, causative mutations are known in at least five disease genes (UMOD, MUC1, REN, HNF1B, SEC61A1) [1] and one can expect that even more disease genes exist. There are already strong international collaborations to define the clinical course of ADTKD [2] and to evaluate a targeted therapy in clinical trials [3]. Clinical registries form the basis for the inclusion of patients, preferably at an early stage of the disease. Such a registry already exists in the USA and is currently being established in Europe (ADTKD-Net) as part of the European Joint Program on Rare Diseases (EJP RD). Due to its non-specific and variable clinical characteristics, ADTKD is often misdiagnosed or not diagnosed at all. Experts therefore suspect a high number of unreported cases. There are also challenges in genetic diagnostics. While next generation sequencing (NGS) panels have been established for ADTKD, they are usually unable to detect pathogenic MUC1 variants due to their specific location in the genome. This is the insertion of an additional cytosine (dupC) in a VNTR (Variable Number of Tandem Repeats) domain of the MUC1 gene, which cannot be detected by NGS and therefore requires special procedures such as SnaPshot Minisequencing [4] or VNtyper [5]. For instance, there are only two laboratories that can perform this specific MUC1 testing in Germany to date. The aim of this study is to assess the status quo of ADTKD diagnostics in Europe. We hypothesize that there is a lack of appropriate structures to adequately and reliably diagnose ADTKD, notably ADTKD-MUC1. The study is intended to help identify deficits and obstacles in order to address these in a targeted manner. Methods We used Survey Monkey to create a digital survey, which we sent by email to around 50 European ADTKD experts. They were asked to answer 7 key questions (Fig. 1). For the selection of suitable ADTKD experts, we use various sources such as publications on ADTKD in PubMed, the Expert Finder and the European Patient Advocacy Groups (ePAG) in the European Reference Network for Rare Kidney Diseases (ERKNet) and our own network. Our aim is to cover at least the 30 largest countries in Europe in terms of population. Results Results will be presented at the ERA conference. Conclusion With our survey we would like to substantiate the hypothesis that the possibilities of molecular diagnostics of ADTKD in Europe are currently insufficient. Based on our results, short and long-term measures should be taken to remedy potential deficits so that as many patients as possible can be identified and have access to therapeutic options in the future. Another interesting aspect is the awareness of ADTKD among European nephrologists. This could be a future activity of our patient organization.