Cardiovascular outcomes in Fabry disease are linked to severity of chronic kidney disease.
OBJECTIVE
Assess the impact of end-stage renal disease (chronic kidney disease stage 5 (CKD5)) on cardiovascular outcomes in patients with Fabry disease on enzyme replacement therapy.


BACKGROUND
Fabry disease, an X-linked lysosomal storage disease, causes hypertrophic cardiomyopathy and cardiovascular dysfunction.


METHODS
Cardiac and renal function of 25 male patients with Fabry disease were analysed at 0, 1, 2, 5, 7 and 10 years after initiation of treatment. Patients were grouped at baseline into those with CKD5 (n=10) and those without (n=15). ECG and echocardiography were performed 6 and 12 monthly, respectively, while renal function was measured yearly.


RESULTS
After 10 years of treatment, cardiac and renal function in non-CKD5 patients remained unchanged. In contrast, CKD5 was associated with worse baseline cardiac parameters and progressive LV hypertrophy. LV mass index grew by 35.4±31.8 g/m(2.7) in CKD5 versus 5.7±7.9 g/m(2.7), p=0.044 in non-CKD5, predominantly due to increased interventricular septal wall thickness (7.7±5.5 mm vs 1.3±1.7 mm, p=0.003). Cardiovascular events, including sudden death, arrhythmia and pacing device insertion, occurred in 100% patients with CKD5 (21 events) and 26% non-CKD5 patients (7 events), p<0.0001. Additionally, estimated LV filling pressure (E/Ea) was significantly higher in patients having cardiovascular events (21.1±7.7 vs 12.5±4.5, p=0.008) irrespective of renal function.


CONCLUSIONS
End-stage renal disease was the strongest indicator of cardiovascular disease progression in Fabry disease. Enzyme replacement initiated prior to CKD5 was associated with stability in cardiac and renal disease while patients with CKD5 showed ongoing deterioration. Additionally, E/Ea ≥15 may predict risk of cardiac events.
Department of Nephrology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Andrew S
http://orcid.org/0000-0003-4803-6830
AS
Talbot
Department of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Nigel T
NT
Lewis
Department of Nephrology, Royal Melbourne Hospital, Melbourne, Victoria, Australia Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Kathy M
KM
Nicholls
D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D018572:Disease-Free Survival; D015150:Echocardiography, Doppler; D004562:Electrocardiography; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D005919:Glomerular Filtration Rate; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D006435:Renal Dialysis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D016277:Ventricular Function, Left; D055815:Young Adult; D000519:alpha-Galactosidase / Q000627:therapeutic use
D000519:alpha-Galactosidase
QUALITY OF CARE AND OUTCOMES; RENAL DISEASE