Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: The prevalence of end stage renal disease (ESRD) of unknown aetiology in adult patients accounts for almost 20% of all dialysis patients in Europe. Genetic causes for renal disease are well established in paediatric nephrology. Recent studies suggest that the proportion of adult patients with a causal genetic variant has been underestimated dramatically. Next generation sequencing (NGS) substantially improved the identification of mutations leading to ESRD with a great impact on the management of such patients. An accurate genetic diagnosis helps identifying comorbidities at an early stage, stratifying the risk of recurrence as well as evaluating potential living kidney donor candidates. Therefore, this now cost- and time-efficient diagnostic approach should be aimed at whenever possible.
*Methods: Over 300 adult patients are listed for kidney transplantation at our center. Patients with ESRD of unknown aetiology at an age below 40, positive family history and/or typical extrarenal manifestations have been selected. These pre-selected patients were analyzed for causal genetic variants by NGS-based sequencing methods.
*Results: 25% of all patients awaiting kidney transplantation (n=316) were diagnosed with ESRD of unknown aetiology. Within this group we determined more than 10 families showing nephropathies with distinct patterns of inheritance. So far, we identified causal genetic variants in the following genes: Uromodulin (UMOD), MUCIN-1 (MUC-1), LIM Homeobox Transcription Factor 1 Beta (LMX1B), Hepatocyte Nuclear Factor (HNF1ß) and Alpha-5-Collagen-Typ-IV (COL4A5). For the latter we are the first to demonstrate a pedigree and a genotype-phenotype-association for this novel genetic variant.
*Conclusions: Hereditary nephropathies are very difficult to diagnose clinically and are therefore likely to be underestimated regarding frequency and significance. This highlights the importance of NGS-based genetic testing in patients with ESRD of unknown aetiology and a positive family history with regards to kidney transplantation. Selection of an appropriate NGS-approach and interpretation of the obtained data is challenging and requires a multidisciplinary work combining the expertise of geneticists and nephrologists. With this study we hope to raise awareness and promote the understanding of rare hereditary nephropathies with adult onset.
To cite this abstract in AMA style:Leenen E, Beck B, Joerres A, Weidemann A. Elucidating the Genetic Background of End Stage Renal Disease of Unknown Aetiology in Patients Listed for Kidney Transplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/elucidating-the-genetic-background-of-end-stage-renal-disease-of-unknown-aetiology-in-patients-listed-for-kidney-transplantation/. Accessed October 30, 2020.
« Back to 2020 American Transplant Congress