Abstract: SA-PO560
Genotype and Renal Outcomes in Alport Syndrome: A Retrospective Cohort Study Using National Registry of Rare Kidney Diseases (RaDaR) Data
Session Information
- Genetic Diseases: Diagnosis
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1102 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Wong, Katie, UK Renal Registry, Bristol, Bristol, United Kingdom
- Pitcher, David, UK Renal Registry, Bristol, Bristol, United Kingdom
- Turner, A. Neil, University of Edinburgh, Edinburgh, United Kingdom
- Bramham, Kate, King's College London, London, London, United Kingdom
- Gale, Daniel P., University College London, London, London, United Kingdom
Background
Alport syndrome (AS) is the second commonest cause of inherited kidney failure, resulting from pathogenic variants in COL4A3, COL4A4, and COL4A5 genes. This study investigated the renal outcomes associated with pathogenic variant types in a UK cohort of patients diagnosed with AS.
Methods
RaDaR data is linked with the UK Renal Registry for renal outcomes and Regional Genetics hubs for genetics reports.
Pathogenic variants were classified into 1)Non-protein length altering 2)Protein length altering. Kaplan-Meier analysis and the log rank statistic were used to compare survival curves, stratified by pathogenic variant type, for a)time between last eGFR ≥90 and last eGFR ≥30 (“therapeutic window”) b)age at KRT start c)kidney transplant graft survival, censored for death.
Analyses were run comparing variant type for 1) COL4A5 males 2) COL4A5 females 3) Heterozygous COL4A3 or COL4A4 variants 4) Homozygous or 2 COL4A3 or COL4A4 variants.
Results
Genetic report data were available for 182/914 (20%) AS patients recruited to RaDaR (Figure 1). 167/182 had a detected pathogenic mutation (92%). 46 (25%) underwent kidney transplantation. No significant difference in time to KRT by variant type was observed in males or females with COL4A5 variants (p=0.17, p=0.06 respectively). Graft survival and time in therapeutic window were not significantly different between variant type for any group.
Conclusion
We did not observe the previously reported correlation between variant type and renal outcomes in males with COL4A5 variants. Linkage of the RaDaR AS cohort with genetic report data is actively ongoing; further correlations may be observed with larger numbers.