NDT Advance Access published online on October 15, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp528
Scoring system for renal pathology in Fabry disease: report of the International Study Group of Fabry Nephropathy (ISGFN)
1 Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA 2 Department of Pathology, Haukeland University Hospital 3 Section of Pathology, The Gade Institute 4 Department of Medicine, Haukeland University Hospital 5 Institute of Medicine, University of Bergen, Bergen, Norway 6 Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA 7 Institute of Pathology, Geneva University Hospital, Geneva, Switzerland 8 Transplanatation Centre, Centre Hospitalier Universitaire Vaudois, University Hospital of Lausanne, Lausanne, Switzerland 9 Department of Pathology 10 Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada 11 Faculty of Medicine, Institute of Pathology, University of Ljubljana, Ljubljana, Slovenia 12 Department of Nephrology and Dialysis, General Hospital, Slovenj Gradec, Slovenia 13 Department of Cellular Pathology, University College London Medical School, Royal Free Hospital, London, UK 14 Centre for Nephrology, Royal Free Hampstead NHS Trust and University College London, London, UK 15 Department of Histopathology 16 Department of Metabolic Disease, Salford Royal Hospital NHS Foundation Trust, Salford, Manchester, UK 17 Department of Pathology 18 Department of Nephrology, Necker Hospital, University Paris Descartes, Paris, France 19 Department of Pathology 20 Department of Nephrology and Human Genetics, Faculty of Medicine, Hospital São João, Porto, Portugal 21 Department of Pathology 22 Department of Medicine, University of Würzburg, Würzburg, Germany 23 Department of Biostatistics 24 Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
Correspondence and offprint requests to: Agnes B. Fogo; E-mail: agnes.fogo{at}vanderbilt.edu
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Abstract |
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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 µmol/l); estimated glomerular filtration rate was 81.7 ml/min/1.73 m2 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.
Keywords: chronic kidney disease; Fabry disease; pathology; sclerosis; scoring
Received for publication: 8. 3.09
Accepted in revised form: 15. 9.09