Resumen
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.
| Idioma original | English |
|---|---|
| Páginas (desde-hasta) | 2168-2177 |
| Número de páginas | 10 |
| Publicación | Nephrology Dialysis Transplantation |
| Volumen | 25 |
| N.º | 7 |
| DOI | |
| Estado | Published - jul. 2010 |
Nota bibliográfica
Funding Information:Acknowledgements. The authors would like to acknowledge the efforts of Ellen Donnert at Vanderbilt University; Department of Pathology, for coordinating the exchange of slides sets and preparation of the scoring sheets. Dr Gary Cutter of the Department of Biostatistics, University of Alabama at Birmingham, provided guidance for the statistical analyses in this paper. Dr Noël would like to acknowledge the collaborative effort of Dr B. Laurent, Dr D.P. Germain, Professor G. Choukroun, and Dr C. Cordonnier to contribute Fabry nephropathy biopsy specimens. The patients described in this report are registered in the Fabry Outcome Survey (Shire Human Genetic Therapies, Boston, MA, USA) and the Fabry Registry (Genzyme Corporation, Cambridge, MA, USA); Institutional Review Board approval was obtained at each centre as part of their registry activity. A.B.F, D.G.W, F.Br., L.B. and J.P.O are members of the Steering Committee of the ISGFN, chaired by J.P.O. A preliminary report of these findings was presented at the 2006 Annual Meeting of the American Society of Nephrology in San Diego, CA, USA [37]. This work was supported by an unrestricted educational grant from Genzyme Corporation, Cambridge, MA, USA, and in addition, Hans Ebels (Genzyme Corporation) assisted with the preparation of the manuscript for submission. The authors are fully responsible for the contents of this paper. Partial support for the analyses was provided by the UAB-UCSD O’Brien Core Center (NIH 1P30 DK 079337).
Funding Information:
Conflict of interest statement. A.B.F. has received consultant and past grant support from Genzyme Corporation. L.B. has received travel assistance from Genzyme Corporation. E.S. has received speaker fees from Gen-zyme Corporation. W.J.C. has received travel assistance from Genzyme Corporation. S.M. has received travel assistance from Genzyme Corporation. F.Ba. has received speaker fees and travel assistance from Genzyme Corporation and Shire Human Genetic Therapies Inc. L.G. has nothing to disclose. M.W. has received speaker fees, consultant fees and/or research support from Genzyme Corporation, Shire Human Genetic Therapies Inc. and Amicus Therapeutics Inc. D.F. has received travel assistance from Gen-zyme Corporation. B.V. has received speaker fees and research grant support from Genzyme Corporation and Shire Human Genetic Therapies Inc. A.J.H. has received travel assistance from Genzyme Corporation. A.B. has received travel assistance from Genzyme Corporation. R.R. has nothing to disclose. S.W. is a member of the European Advisory Board of the Fabry Registry, sponsored by Genzyme Corporation, and is compensated for the services by Genzyme Corporation. S.W. is a paid consultant for Genzyme Corporation on matters relating to Fabry disease, has received research grants from Genzyme Corporation related to Fabry disease, and speaking fees from Genzyme Corporation and Shire Human Genetic Therapies Inc. L.H.N. has received travel assistance from Genzyme Corporation. J.P.G. has received travel assistance from Genzyme Corporation and Transkary-otic Therapies Inc. and is a consultant for Genzyme Corporation but did not receive consultancy fees. C.V. has received a non-restricted research grant from Genzyme Corporation. J.P.O. is a member of the European Advisory Board of the Fabry Registry, sponsored by Genzyme Corporation, and has received speaker fees and research support from Genzyme Corporation. J.M. has received travel assistance from Genzyme Corporation. F.Br. has received travel assistance and speaking fees from Genzyme Corporation and Shire Human Genetic Therapies Inc. D.G.W. is a paid consultant for Genzyme Corporation and has received speaker fees and research support from Genzyme Corporation.
ASJC Scopus Subject Areas
- Nephrology
- Transplantation