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 Lyon

Fabry disease X-linked inherited lysosomal storage disorder deficiency of -galactosidase A progressive accumulation of globotriaosylceramide (Gb 3 )

Fabry disease Accumulation in many types of cells nervous system skin heart kidney vascular endothelial cells gastro- intestinal symptoms 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 Time from start of -Gal treatment (years) inulin clearance (ml/min/1.73 m 2 ) < > 30 alb/creat (mg/mmol) (n = 6) (n = 9) (n = 10) mean decline in GFR (ml/min/1.73 per year) -0.8 ± ± ± 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 Gb 3 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