Abstract: SA-PO805
Evaluation of Long-Term Renal Outcomes in Fabry Disease: A Single-Centre Prospective Cohort Study in North-West England
Session Information
- Genetic Diseases: Glomerulopathies - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Mannan, Fahmida, Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, England, United Kingdom
- Wiltshire, Ryan, Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, England, United Kingdom
- Chinnadurai, Rajkumar, Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, England, United Kingdom
- Kalra, Philip A., Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, England, United Kingdom
- Jovanovic, Ana, Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, England, United Kingdom
Group or Team Name
- Salford Fabry Observational Study.
Background
Fabry disease (FD) is a rare X-linked lysosomal storage disorder whereby deficiency of α-galactosidase-A results in progressive renal impairment and end-stage renal failure (ESRF). International recommendations suggest enzyme replacement therapy (ERT) in those with early signs of renal dysfunction, yet limited data exist on long-term outcomes.
Methods
395 patients were included from a national FD database from conception to 1 February 2022. Baseline data include FD mutation, diagnosis and ERT initiation dates, renal biochemical values, co-morbidities and medications. Those on renal replacement therapy (RRT) were excluded. Rapidly progressive renal dysfunction was defined as eGFR decline of > 1 ml/min/year. Primary outcomes include ESRF requiring RRT, all-cause mortality, and non-fatal cardiovascular events (NFCVE).
Results
395 patients (M=172;F=223) with median follow-up of 6.4 years were analysed. Males received more treatment (147 v 92, p<0.001), had RRT (12 v 1, p<0.001), experienced NFCVE (75 v 42, p<0.001) and all-cause mortality (21 v 8, p<0.001). Sub-cohort analysis (n=260) showed faster eGFR decline was not predictive of RRT, but associated with higher rates of NFCVE (52 v 50, p=0.01) and all-cause mortality (17 v 8, p=0.004;fig.1). Multivariate regression demonstrated only advancing age associated with faster renal disease progression (OR:1.05; 95% CI: 1.02-1.07; p<0.001).
33 developed CKD during median follow-up of 10.9 years. Genetic analysis showed highest prevalence of the commonest late-onset variant c.644A>G/p.N215S. 18(55%) started ERT, and 6 discontinued due to gastrointestinal intolerance or tiredness. 15(45%) experienced NFCVE, with stroke/TIA being commonest (n=6).
Conclusion
Our study supports early initiation of ERT, prior to onset of any renal decline, and advanced age a predictor of adverse outcomes.
Figure 1: Rate of survival (all-cause mortality)of faster/slower eGFR progressors. Log-rank p<0.001