Journal Article

Cardiovascular outcomes in Fabry disease are linked to severity of chronic kidney disease

Lewis, Nigel T, Nicholls, Kathy M, Talbot, Andrew S

2015

Overview

Objectives 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/m2.7 in CKD5 versus 5.7±7.9 g/m2.7, 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.

• Publisher: BMJ Publishing Group LTD
• Subject: Adolescent / Adult / alpha-Galactosidase - therapeutic use / Cardiomyopathy / Data analysis / Disease Progression / Disease-Free Survival / Echocardiography, Doppler / Electrocardiography / Enzyme Replacement Therapy / Enzymes / Fabry Disease - complications / Fabry Disease - diagnosis / Fabry Disease - drug therapy / Fabry Disease - mortality / Glomerular Filtration Rate / Heart attacks / Humans / Hypertrophy, Left Ventricular - diagnosis / Hypertrophy, Left Ventricular - etiology / Hypertrophy, Left Ventricular - mortality / Hypertrophy, Left Ventricular - physiopathology / Hypertrophy, Left Ventricular - therapy / Kidney diseases / Kidney Failure, Chronic - diagnosis / Kidney Failure, Chronic - etiology / Kidney Failure, Chronic - mortality / Kidney Failure, Chronic - physiopathology / Kidney Failure, Chronic - therapy / Kidney Transplantation / Male / Middle Aged / Mortality / Mutation / Predictive Value of Tests / Renal Dialysis / Retrospective Studies / Severity of Illness Index / Statistical analysis / Studies / Time Factors / Treatment Outcome / Ventricular Dysfunction, Left - diagnosis / Ventricular Dysfunction, Left - etiology / Ventricular Dysfunction, Left - mortality / Ventricular Dysfunction, Left - physiopathology / Ventricular Dysfunction, Left - therapy / Ventricular Function, Left / Young Adult