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Kidney Week

Abstract: TH-PO709

Tackling Undetermined ESRD by Whole Nephrome Sequencing in Adult Patients Waiting for Kidney Transplantation

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic


  • Ottlewski, Isabel, University Hospital Leipzig, Leipzig, Germany
  • Muench, Johannes, University Hospital Leipzig, Leipzig, Germany
  • Wagner, Timo, Bioscientia, Ingelheim, Germany
  • Bergmann, Carsten, Bioscientia, Ingelheim, Germany
  • Bachmann, Anette, University Hospital Leipzig, Leipzig, Germany
  • Lindner, Tom H., University Hospital Leipzig, Leipzig, Germany
  • Seehofer, Daniel, University Hospital Leipzig, Leipzig, Germany
  • Halbritter, Jan, University Hospital Leipzig, Leipzig, Germany

End-stage renal disease (ERSD) of undetermined etiology constitutes a significant clinical challenge, notably in kidney transplantation (KT). In absence of renal histology, genetic analysis may further elucidate ESRD etiology. To date, hereditary kidney disease is thought to represent < 10% of ESRD patients, mainly attributed to ADPKD. In recent years, however, a multitude of additional rare genetic ESRD conditions have been discovered without being yet systematically considered in clinical routine. To tackle the issue of undetermined ESRD prior to KT, we aimed to broadly analyze for genetic causes in patients on the waitlist.


Patients on the local KT-waitlist (n=134) were stratified based on their presumed etiologies: i) non- hereditary (n=56); ii) hereditary, including clinically diagnosed ADPKD (n=29); iii) undetermined, including biopsy-proven FSGS (n=49). The latter patients were analyzed by whole “nephrome” sequencing, comprising more than 290 ESRD-associated OMIM-genes.


An undetermined etiology was found in 36% of individuals (49/134) on the waitlist, 40% of whom reported a positive family history. We detected a robust genetic diagnosis in 24% (12/49). The genes COL4A3/5 were found most frequently mutated in undetermined ESRD. Taken together, hereditary nephropathies, including ADPKD, were identified in 31% (41/134) of the overall cohort. By significantly increasing the proportion of hereditary diagnoses (from n=29 to n=41, p<0,05), the rate of undetermined ESRD went down from n=49 to n=37 (p<0,05).


By this pilot study, we demonstrate the beneficial use of whole “nephrome” sequencing to significantly reduce the proportion of undetermined ESRD prior to KT. In absence of renal histology or unspecific histological conditions, such as FSGS or TMA, genetic analysis may not only provide a robust diagnosis but helps differentiating recurrent from non-recurrent etiologies, thereby contributing to personalized KT management and adequate evaluation of potential living donors.