Agalsidase therapy in patients with Fabry disease on renal replacement therapy: a nationwide study in Italy.
BACKGROUND
In Fabry disease, end-stage renal disease (ESRD) and severe neurologic and cardiac complications represent the leading causes of late morbidity and mortality. A comprehensive Italian nationwide survey study was conducted to explore changes in cardiac status and renal allograft function in Fabry patients on renal replacement therapy (RRT) and enzyme replacement therapy (ERT).


METHODS
This study was designed as a cross-sectional survey study with prospective follow-up. Of the 34 patients identified via searches in registries, 31 males and 2 females who received RRT and ERT (agalsidase beta in 30 patients, agalsidase alpha in 3) were included. Left ventricular mass index (LVMI), interventricular septal thickness at end diastole (IVSD), left ventricular posterior wall thickness (LVPWT) and renal allograft function were assessed at ERT baseline and subsequently at yearly intervals.


RESULTS
The patients in the dialysis and transplant groups had been started on dialysis at age 42.0 and 37.1 years (mean), respectively, and patients in the transplant group received their renal allograft at age 39.8 years (mean). The mean age at the start of ERT was similar, 44.1 and 44.6 years, respectively. The mean RRT follow-up was 61.1 and 110.6 months for dialysis and transplant patients, respectively, whereas the ERT duration was 45.1 and 48.4 months, respectively. Cardiac parameters increased in dialysis patients. In transplant patients, mean LVMI seemed to plateau during agalsidase therapy at a lower level as compared to baseline. Decline in renal allograft function was relatively mild (-1.92 ml/min/year). Agalsidase therapy was well tolerated. Serious ERT-unrelated events occurred more often in the dialysis group.


CONCLUSIONS
Kidney transplantation should be the standard of care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on ERT may do better than patients remaining on maintenance dialysis. Larger, controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is able to change the trajectory of cardiac disease and can preserve graft renal function.
Mignani
Renzo
R
Department of Nephrology and Dialysis, Infermi Hospital, via Settembrini 2, 47900 Rimini, Italy. rmignani@auslrn.net
Feriozzi
Sandro
S
Pisani
Antonio
A
Cioni
Antonio
A
Comotti
Cristina
C
Cossu
Maria
M
Foschi
Annalisa
A
Giudicissi
Antonio
A
Gotti
Eliana
E
Lozupone
Vito Antonio
VA
Marchini
Francesco
F
Martinelli
Fabrizio
F
Bianco
Francesco
F
Panichi
Vincenzo
V
Procaccini
Deni Aldo
DA
Ragazzoni
Elena
E
Serra
Andrea
A
Soliani
Fausto
F
Spinelli
Letizia
L
Torti
Giacomo
G
Veroux
Massimiliano
M
Cianciaruso
Bruno
B
Cagnoli
Leonardo
L
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy* / Q000628:therapy*; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D007527:Isoenzymes / Q000627:therapeutic use*; D007558:Italy; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000628:therapy; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012042:Registries; D017582:Renal Replacement Therapy; D018487:Ventricular Dysfunction, Left / Q000209:etiology; D000519:alpha-Galactosidase / Q000627:therapeutic use*
D007527:Isoenzymes; D011994:Recombinant Proteins; D000519:alpha-Galactosidase; C459420:agalsidase beta