title: Scoring system for renal pathology in Fabry disease: report of the International Study Group of Fabry Nephropathy (ISGFN).
abstract: BACKGROUND
  In Fabry nephropathy, alpha-galactosidase deficiency leads to accumulation of glycosphingolipids in all kidney cell types, proteinuria and progressive loss of kidney function.
  
  
  METHODS
  An international working group of nephrologists from 11 Fabry centres identified adult Fabry patients, and pathologists scored histologic changes on renal biopsies. A standardized scoring system was developed with a modified Delphi technique assessing 59 Fabry nephropathy cases. Each case was scored independently of clinical information by at least three pathologists with an average final score reported.
  
  
  RESULTS
  We assessed 35 males (mean age 36.4 years) and 24 females (43.9 years) who mostly had clinically mild Fabry nephropathy. The average serum creatinine was 1.3 mg/dl (114.9 micromol/l); estimated glomerular filtration rate was 81.7 ml/min/1.73 m(2) and urine protein to creatinine ratio was 1.08 g/g (122.0 mg/mmol). Males had greater podocyte vacuolization on light microscopy (mean score) and glycosphingolipid inclusions on semi-thin sections than females. Males also had significantly more proximal tubule, peritubular capillary and vascular intimal inclusions. Arteriolar hyalinosis was similar, but females had significantly more arterial hyalinosis. Chronic kidney disease stage correlated with arterial and glomerular sclerosis scores. Significant changes, including segmental and global sclerosis, and interstitial fibrosis were seen even in patients with stage 1-2 chronic kidney disease with minimal proteinuria.
  
  
  CONCLUSIONS
  The development of a standardized scoring system of both disease-specific lesions, i.e. lipid deposition related, and general lesions of progression, i.e. fibrosis and sclerosis, showed a spectrum of histologic appearances even in early clinical stage of Fabry nephropathy. These findings support the role of kidney biopsy in the baseline evaluation of Fabry nephropathy, even with mild clinical disease. The scoring system will be useful for longitudinal assessment of prognosis and responses to therapy for Fabry nephropathy.
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA. agnes.fogo@vanderbilt.edu
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
authors.forename: Leif
authors.initials: L
authors.lastname: Bostad
authors.forename: Einar
authors.initials: E
authors.lastname: Svarstad
authors.forename: William J
authors.initials: WJ
authors.lastname: Cook
authors.forename: Solange
authors.initials: S
authors.lastname: Moll
authors.forename: Federic
authors.initials: F
authors.lastname: Barbey
authors.forename: Laurette
authors.initials: L
authors.lastname: Geldenhuys
authors.forename: Michael
authors.initials: M
authors.lastname: West
authors.forename: Dusan
authors.initials: D
authors.lastname: Ferluga
authors.forename: Bojan
authors.initials: B
authors.lastname: Vujkovac
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Howie
authors.forename: Aine
authors.initials: A
authors.lastname: Burns
authors.forename: Roy
authors.initials: R
authors.lastname: Reeve
authors.forename: Stephen
authors.initials: S
authors.lastname: Waldek
authors.forename: Laure-Hélène
authors.initials: LH
authors.lastname: Noël
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Grünfeld
authors.forename: Carmen
authors.initials: C
authors.lastname: Valbuena
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Oliveira
authors.forename: Justus
authors.initials: J
authors.lastname: Müller
authors.forename: Frank
authors.initials: F
authors.lastname: Breunig
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
mesh_terms: D000328:Adult; D001706:Biopsy; D018450:Disease Progression; D000795:Fabry Disease / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005355:Fibrosis / Q000473:pathology; D005919:Glomerular Filtration Rate / Q000502:physiology; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D050199:Podocytes / Q000473:pathology; D012720:Severity of Illness Index; D012727:Sex Characteristics