Dialysis and transplantation in Fabry disease: indications for enzyme replacement therapy.
ESRD is a major cause of morbidity and premature mortality in Fabry disease, particularly in classically affected males. The decline of renal function in Fabry nephropathy is adversely affected by male gender, advanced chronic kidney disease (CKD), and severe proteinuria. The diagnosis of Fabry nephropathy may be missed if not specifically addressed in progressive CKD and patients have been first identified in screening programs of dialysis patients. Fabry patients have worse 3-year survival rates on dialysis as compared with nondiabetic controls. The 5-year survival rate of transplanted Fabry patients is also lower than that of controls. However, because Fabry nephropathy does not recur in the allograft and transplanted Fabry patients appear to have better overall outcomes than those maintained on dialysis, kidney transplantation should be recommended as a first choice in renal replacement therapy (RRT) for Fabry disease. Appropriately designed and powered studies are not available to answer the question whether enzyme replacement therapy (ERT) influences outcomes, the course of cardiomyopathy, events, or survival in Fabry patients on RRT. The authors are not aware of compelling indications for ERT in RRT patients because progression of cardiomyopathy was documented during ERT. Whether the excess mortality risk of Fabry patients on RRT can be prevented by ERT is unknown. Despite observational reports of symptomatic improvement, the available evidence supporting ERT for such patients is not compelling enough. To clarify this issue, studies are needed to test the effectiveness of agalsidases in preventing cardiac and cerebrovascular complications in Fabry patients with ESRD.
Mignani
Renzo
R
Department of Nephrology and Dialysis, Infermi Hospital, Rimini, Italy.
Feriozzi
Sandro
S
Schaefer
Roland M
RM
Breunig
Frank
F
Oliveira
João Paulo
JP
Ruggenenti
Piero
P
Sunder-Plassmann
Gere
G
D018450:Disease Progression; D056947:Enzyme Replacement Therapy / Q000009:adverse effects; D019317:Evidence-Based Medicine; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000601:surgery / Q000628:therapy; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D006435:Renal Dialysis / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000009:adverse effects / Q000627:therapeutic use*
D000519:alpha-Galactosidase