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Kidney Week

Abstract: PO1293

The Emerging Role of Whole-Genome Investigation to Identify Undetected Nephropathies: The HIDDEN Study

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Mallett, Andrew John, Townsville Hospital and Health Service, Townsville, Queensland, Australia
  • Mallawaarachchi, Amali, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
  • Stark, Zornitza, Murdoch Childrens Research Institute, Parkville, Victoria, Australia
  • Simons, Cas, Murdoch Childrens Research Institute, Parkville, Victoria, Australia
  • Quinlan, Catherine, Murdoch Childrens Research Institute, Parkville, Victoria, Australia
  • Patel, Chirag, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Group or Team Name

  • The KidGen Collaborative
Background

5% of Australian and New Zealand patients commencing kidney replacement therapy have an uncertain kidney disease aetiology. New approaches and tools are required to resolve such diagnostic odysseys. WGS is an emerging diagnostic technology whose role in this setting is unclear. We sought to determine the diagnostic yield of clinical whole genome sequencing (WGS) in individuals with unexplained end stage kidney disease (ESKD).

Methods

Adult and paediatric patients reaching Chronic Kidney Disease Stage 5 before 51 years of age without an identified aetiology were prospectively recruited through an Australian national network of 18 clinics. Eligibility was determined by a national clinical committee based on pre-specified criteria.
Clinically-accredited WGS analysis was undertaken with a curated “KidneyOme” virtual panel of genes associated with Mendelian kidney disorders. A genomic diagnosis constituted a KidneyOme result of pathogenic or likely pathogenic variant/s of appropriate zygosity.

Results

168 individuals were referred (2018-2021) of whom 147 were approved and 104 consented. Of these, 40 (38.5%) were female and median age was 43yrs; 41 (39.4%) reached ESKD before 30yrs and 63 (60.6%) had undergone native kidney biopsy. Of 50 results returned to date, 7 (14%) were diagnostic, including both autosomal dominant (4/7) and recessive (3/7) inheritance patterns with 6/7 having a family history of CKD. A further 14/50 had variants of uncertain significance. One diagnosis was due to a copy number variation.
The KidneyOme virtual panel curation of 384 genes is publicly available in PanelApp-Australia.

Conclusion

One in seven patients with ESKD of uncertain aetiology had an undetected underlying monogenic cause for their kidney disease. Application of KidneyOme with WGS has diagnostic utility and should be considered in younger patients with unexplained renal failure.

Funding

  • Government Support – Non-U.S.