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Kidney Week

Abstract: FR-PO598

Characterization of Monogenic Kidney Disease in Patients over 60 Years of Age

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Elhassan, Elhussein Aamir Elzein, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Benson, Katherine A., Royal College of Surgeons in Ireland, Dublin, Dublin, Ireland
  • Cavalleri, Gianpiero, Royal College of Surgeons in Ireland, Dublin, Dublin, Ireland
  • Conlon, Peter J., Beaumont Hospital, Dublin, Ireland
Background

Approximately 10% of adults with chronic kidney disease (CKD) have monogenic forms of the disease. However, the prevalence of monogenic kidney diseases in the over-60 population is not well characterized.

Methods

For genetic screening in this cohort with suspected monogenic kidney disease, excluding polycystic kidney disease, we utilized gene-panel and exome sequencing. The purpose of this study was to assess the diagnostic yield of clinically validated disease-causing variants and to compare the clinical characteristics of solved and unsolved cohorts.

Results

Genetic testing was performed for 113 adults (n= 93 families) with a median age at recruitment of 69 years (IQR: 64 - 73). 83.3% participants reported a family history of CKD and 52.2% were females. At last follow up, 84 (75.7%) individuals progressed to kidney failure at a median age of 57 years [IQR: 41.5 – 65]. We were able to demonstrate likely-pathogenic/pathogenic variant in 37/113 (32.7%), encompassing 13 distinct monogenic entities. Disease-causing variants in three phenotypes accounted for up to 76% of solved cases. These included MUC1 (n=6), UMOD (n=3), HNF1B (n=5) and DNAJB11 (n=1) associated with tubulointerstitial kidney disease; COL4A5 (n=4) and monoallelic COL4A3 (n=4) associated with Alport–related kidney disease; and INF2 (n=5) associated with focal segmental glomerulosclerosis. We identified disease-causing variants in the CLCN5 gene associated with Dent disease type 1 in an additional 3 (2.6%) individuals. In 32% (n=8) of the 25 patients referred with a priori diagnosis of CKD of undetermined cause were found to have a known monogenic cause. There was no difference in age at initial presentation [45.4 vs. 46 years; p = 0.863] and age at kidney failure [52.8 vs. 52.8 years; p = 0.747] between individuals with monogenic disease and those without. A family history of CKD was an independent predictor of a genetic diagnosis [odds ratio: 5; 95% CI: 1.1 - 23.3, p = 0.040], with a higher proportion of solved cases than unsolved cases [94.4% vs. 77.7%, p = 0.02].

Conclusion

We estimated that about a third of this cohort over 60 years old with suspected inherited CKD would have a monogenic nephropathy. Awareness of monogenic nephropathies, particularly in this population group, should permit family counselling and individualized treatment.