1 / 25

RENAL INVOLVEMENT IN FABRY DISEASE

RENAL INVOLVEMENT IN FABRY DISEASE. Sandro Feriozzi Nephrology and Dialysis AUSL/VT Italy. BIOCHIMICA & GENETICA. Bishop PNAS 1988. GENETICA. TRASMISSIONE IPOTESI DI LYON.

verda
Download Presentation

RENAL INVOLVEMENT IN FABRY DISEASE

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. RENAL INVOLVEMENT IN FABRY DISEASE Sandro Feriozzi Nephrology and Dialysis AUSL/VT Italy

  2. BIOCHIMICA & GENETICA Bishop PNAS 1988

  3. GENETICA TRASMISSIONE IPOTESI DI LYON

  4. NATURAL HISTORY OF FABRY NEPHROPATHY Over the last 10 years something has been changed: Pathogenesis Prevalence Clinical picture ( consistent with) Treatment of the nephropathy Urinary biomarkers 30-35 y.o. 24/h prot <3g eGFR BP  >40 y.o. 24/prot <3g eGFR BP 20 y.o. 24/h prot <3g eGFR: norm. BP: norm tubular defects

  5. PATHOGENESIS OF THE NEPHROPATHY Intracellular deposition of Gb3 podocyte endothelium tubular epithelium cellular damage segmental sclerosis ischemia tubular defects Thadhani Madrid 2002

  6. PODOCYTE & Lyso Gb3 Sanchez-Nino, NDT 2011

  7. PREVALENCE OF FABRY IN DIALYSIS Thadhani, Kidney Int. 2002 Muto JASN 2000 USRDSEDTA - ERAJAPAN prevalence % 42/250.000 83/440.000 2/250 0.0167% 0.0188% 0.8% ITALY JAPAN AUSTRIA prevalence % 16/6378 6/514 4/2480 0,25% 1,2% 0,16% Spada J Inherit Metab Dis 2002 Nakao Kidney Int 2003 Kotanko JASN 2004 In dialysis unit it is reasonable estimate 1 Fabry /100 pts Prevalence 1:17.000 / 1:117.000 (UpToDate 2013 ) Maruyama (CJASN 2013) 47/1453 (3%) pts with low α-gal, but only 3 (0.2%) with LysoGb3 detectable , only 1 with mutation-causing disease

  8. During these years something has been changed : Prevalence Clinical picture (consistent with) Treatment of the nephropaty We will try to evaluate nephrological data from : Proteinuria Hypertension Renal function Clinical aspects

  9. ARTERIAL HYPERTENSION The same results have been reported by Kleinert in FOS AJH 2006 Ortiz, NDT 2008 Hypertension does not appear to be a major contributing factor in the progression Branton JASN 2002

  10. NATURAL RENAL PROGRESSION Schiffmann,NDT 2009

  11. DON ‘T FORGET THE FEMALES IN EARLY DETECTION Events precede diagnosis Events follow diagnosis «Although the signs of disease in women, in general occur later and with slower clinical progression compared with men, women can suffer from all the signs and symptoms of the disease» Parini & Feriozzi , Exp Opin Orphan Drugs 2013 CARDIAC RENAL CEREBROVAS: males females - 40 - 20 0 20 40 60 Years from clinical diagnosis

  12. PLOTS OF eGFR THROUGHOUT THE STUDY Feriozzi , CJASN 2012

  13. Without/ with hypertension ANNUALLY eGFR SLOPE -ml/min/year -ml/min/1,73m2 Feriozzi, CJASN 2012

  14. Tondel JASN 2013

  15. LONG-TERM OUTCOME OF ERT Rombach, OJRD 2013

  16. Cybulla , JN 2012

  17. URINARY BIOMARKERS During these years something has been changed: Prevalence Clinical picture ( consistent with) Treatment of renal signs Urinary biomarkers Rombach PloOne 2012 There was no significant correlation between urine lyso-Gb3 and eGFR. Therefore, lyso-Gb3 is not a good predictive biomarker for kidney involvement. Auray-Blais, Clin Chim Acta 2010

  18. URINARY BIOMARKERS Kistler , Plosone 2012

  19. CONCLUSIONS • Proteinuria and hypertension are risk factors for the • progression of renal disease and should be managed • appropriately • Early detection of renal involvement should be achieved • by regular measurement of GFR and proteinuria in both sexes • Early intervention with ERT and adjunctive therapy can • stabilize renal function or significantly slows down its decline • The role of biomarkers in diagnosis and in monitoring therapy is • promising but not clear yet Waldek & Feriozzi submitted

More Related