Scoring system for renal pathology in Fabry disease: report of the International Study Group of Fabry Nephropathy (ISGFN).
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.
Fogo
Agnes B
AB
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA. agnes.fogo@vanderbilt.edu
Bostad
Leif
L
Svarstad
Einar
E
Cook
William J
WJ
Moll
Solange
S
Barbey
Federic
F
Geldenhuys
Laurette
L
West
Michael
M
Ferluga
Dusan
D
Vujkovac
Bojan
B
Howie
Alexander J
AJ
Burns
Aine
A
Reeve
Roy
R
Waldek
Stephen
S
Noël
Laure-Hélène
LH
Grünfeld
Jean-Pierre
JP
Valbuena
Carmen
C
Oliveira
João Paulo
JP
Müller
Justus
J
Breunig
Frank
F
Zhang
Xiao
X
Warnock
David G
DG
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