Post on 30-Dec-2015
description
ESPN Lyon 2008
What can we expect from enzyme
replacement on renal involvement ?
L Dubourg
Exploration fonctionnelle rénale et Unité de Néphrologie Pédiatrique
Hôpital E Herriot et Université Claude Bernard - INSERM U 820 - Lyon
Fabry disease
X-linked inherited lysosomal storage disorder
deficiency of -galactosidase A
progressive accumulation of
globotriaosylceramide (Gb3)
Fabry disease
Accumulation in many types of cells
nervous system skin heart kidney vascular endothelial
cells
gastro-intestinal symptom
s
pain
skin
early symtoms
brainheartkidney
late symtoms
Renal involvement in Fabry disease
Tondel et al., Am J Kidney Disease, 2008
Renal involvement in Fabry disease
Thurberg et al., kidney int 2002
Organ–specific disease progression
Breuning et al., J Nephrol, 2008
Renal involvement in Fabry disease
Branton et al., Medicine, 2002
Germain et al., J Am Soc Nephrol 2007
Enzyme replacement therapy (ERT)
double-blind placebo controlled period 54 months 58 patients (56 males) mean age 31.1 years Pcr 71 ± 17.7 µmol/l
Thurberg et al. kidney int 2002
Germain et al., J Am Soc Nephrol 2007
ERT
Thurberg et al. kidney int 2002
Germain et al., J Am Soc Nephrol 2007
ERT
Thurberg et al. kidney int 2002
Germain et al., J Am Soc Nephrol 2007
ERT
Thurberg et al. kidney int 2002
Germain et al., J Am Soc Nephrol 2007
ERT
Enzyme replacement therapy (ERT)
eGFR
Germain et al., J Am Soc Nephrol 2007
Enzyme replacement therapy (ERT)
Germain et al., J Am Soc Nephrol 2007
Enzyme replacement therapy
25 patients 21 males : 31.1 ± 2.7 years 4 females : 35.2 ± 8.3 years
0
20
40
60
80
100
120
140
31 2 40 5
Time from start of -Gal treatment (years)
inul
in c
lear
ance
(m
l/min
/1.7
3 m
2 )
< 2.52.5 - 30> 30
alb/creat (mg/mmol)
(n = 6)
(n = 9)
(n = 10)
mean decline in GFR
(ml/min/1.73 per year)
-0.8 ±0.8 -3.5 ± 1.4
-4.9 ± 0.9
ERT
Banikazemi et al., Ann Intern Med, 2007
double-blind placebo controlled median : 18.5 months 82 patients mean age 45 years Pcr 141 ± 44 µmol/l
Branton et al., Medecine, 2002
Fabry disease : onset of symptoms
Fabry disease
Tondel et al., Am J Kidney Disease, 2008
ERT in children
Ries et al., Pediatrics, 2006 Ramaswami et al., Acta Paediatrica, 2007 Wraith et al., J Pediatr, 2008
results
safety
normalisation of Gb3 plasma concentration
decrease in pain and gastro-intestinal symptoms
improvement of autonomic function
decrease in micro-albuminuria
Brenner et al., Curr Opin Nephrol Hypertens, 2004
What can we expect from enzyme replacement on renal involvement ?
Acknowledgments
Département des Maladies Héréditaires du
Métabolisme
Exploration Fonctionnelle rénale et métabolique
Département de Néphrologie Pédiatrique