Deterioration of renal function in young adult patients with fabry disease and proteinuria

Abstract

Objective: We describe the effects of withdrawal of enzyme replacement therapy (ERT) in FD. Methods: Patients were followed up prospectively after ERT withdrawal that occurred due to lack of government reimbursement of this licensed therapy. Results: Seventeen patients (13 males, 4 females) aged 22 to 72 years (mean age, 41.6 years) received ERT intravenously every 2 weeks for a mean of 32.8 months (range, 4-63 months). Three received agalsidase beta (Fabrazyme ® 1 mg/kg); 10 received agalsidase alfa (Replagal ® 0.2 mg/kg); and 4 received both in turn. One patient was lost to follow-up. Mean estimated glomerular filtration rate (eGFR) (adjusted modification of diet in renal disease formula) was 95.9 mL/min/1.73 m 2 pre-ERT, 88.9 mL/min/l.73 m 2 with ERT, and 83.3 mL/min/1.73 m 2 after a mean of 14.8 months off ERT. Class 3 to 5 chronic kidney disease (eGFR, <30 mL/min/1.73 m 2) was 18% pre-ERT and with ERT but 29% post-ERT. Left ventricular mass index was stable throughout. The Mainz Severity Score Index, a measure of the clinical extent of FD, was mean 32.5 pre-ERT, 30.0 with ERT, and 33.8 post-ERT (P = 0.01). Results of the SF-36 Health Survey showed 0 of 15 patients felt better preERT, 6 felt better on ERT, and 1 felt better post-ERT (P = 0.02). No patient had a stroke on or nff ERT. Proteinuria fell with ERT from 805 to 525 mg/d (P = 0.02); proteinuria post-ERT was 567.4 mg/d (NS). Conclusions: With ERT withdrawal of <15 months in FD, there was no change in the severity of the cardiac disease or incidence of stroke. There was reversal of prior improvement in renal function and well-being. These observations are suggestive of prior ERT benefit in FD rather than natural progression of FD. Longer follow-up is needed to confirm these findings due to the heterogeneous nature of this condition.