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Kidney Week

Abstract: PO1294

The Utility of an Inherited Kidney Disease Clinic Employing a Broad Range of Genomic Testing Platforms: Experience of the Irish Kidney Gene Project

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Elhassan, Elhussein Aamir Elzein, Beaumont Hospital, Dublin, Ireland
  • Benson, Katherine A., Royal College of Surgeons in Ireland Department of Molecular and Cellular Therapeutics, Dublin, Ireland
  • Murray, Susan Louise, Beaumont Hospital, Dublin, Ireland
  • Collins, Kane Edmund, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Gilbert, Edmund H., Royal College of Surgeons in Ireland, Dublin, Ireland
  • Connaughton, Dervla M., Western University Schulich School of Medicine & Dentistry, London, Ontario, Canada
  • Kennedy, Claire, Beaumont Hospital, Dublin, Ireland
  • Little, Mark Alan, Saint James's Hospital, Dublin, Ireland
  • Cavalleri, Gianpiero, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Conlon, Peter J., Beaumont Hospital, Dublin, Ireland
Background

Inherited kidney diseases (IKD) are increasingly identified in adult patients. Here we demonstrate the diagnostic and clinical impact of evaluating patients with potential IKD in a dedicated IKD clinic (IKDC) utilising various genomic testing technologies (whole-exome sequencing, comprehensive gene-panel, and dedicated MUC-1 sequencing) and immunostaining.

Methods

We undertook a prospective cohort study of adult patients referred to an academic medical centre with suspected monogenic cause as part of the Irish Kidney Gene Project (IKGP), between 2014 and 2020. Patients with chronic kidney disease (CKD) who had either a positive family history, extrarenal features, or had CKD of ‘’unknown cause’’ (uCKD) were recruited from various centres across Ireland. We attempted to identify disease-causing variants and to assess the impact of the IKDC from diagnostic and clinical perspectives.

Results

During this period, genetic testing was performed for 677 adults (n= 501 families). The median age was 53 years (range, 18-93 years) and 73.9% participants had reported a family history of renal disease. We achieved a molecular diagnostic rate of 56.7 % (384/677). Among the identified disease-causing variants, PKD was the largest cohort (n= 183, 47.8% for PKD1 and PKD2), while mutations in three other causative genes were most prevalent among the remaining identified 42 genes encompassing several Mendelian disorders; MUC-1 (n=31, 8.1%); COL4A5 (n=30, 7.8%); UMOD (n= 12, 3.3%). In the remaining 167 disease-causing variants, excluding PKD, the clinical diagnosis was confirmed in 60.5% and 18% of cases were reclassified. A molecular diagnosis was established in 27 (36.5%) patients with uCKD, implying the end of their diagnostic odyssey. Clinically, a diagnostic kidney biopsy was unnecessary in 13 (7.7%) patients based on the genomic testing, 80 (47.3%) had their treatment plan altered and further 76 (45%) patients had appropriate cascade testing.

Conclusion

The IKDC is a valuable resource and the implementation of a broad range of diagnostic platforms has a direct clinical and therapeutic impact on treatment of patients with CKD.