Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene that obliterate or markedly reduce α-galactosidase A activity. This results in the systemic accumulation of its glycosphingolipid substrates in body fluids and organs, including the kidney. Fabry nephropathy can lead to end-stage renal disease requiring kidney transplantation. Little is known about its long-term outcomes and the overall patient survival after kidney transplantation.
Here, we report 17 Fabry patients (15 male and 2 female subjects) who received kidney transplants and their long-term treatment and follow-up at 4 specialized Fabry centers.
The posttransplant follow-up ranged to 25 years, with a median of 11.5 (range, 0.8-25.5] years. Graft survival was similar, and death-censored graft survival was superior to matched controls. Fabry patients died with functioning kidneys, mostly from cardiac causes. In 2 male subjects 14 and 23 years posttransplant, the grafts had a few typical FD lamellar inclusions, presumably originating from invading host macrophages and vascular endothelial cells.
We conclude that kidney transplantation has an excellent long-term outcome in FD.
This retrospective cohort study suggests that patients with chronic kidney disease due to Fabry disease who receive a kidney transplant and enzyme replacement therapy show long-term patient and graft survival that are at least comparable to matched controls.
1 Department of Cardiology, Inselspital, Bern University Hospital, Bern, Switzerland.
2 Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland.
3 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
4 Department of Nephrology and Hypertension, Inselspital, University of Bern, Bern, Switzerland.
5 Division of Nephrology and Intensive Care Medicine, CVK, Charité Universitätsmedizin, Berlin, Germany.
6 Service of Genetic Medicine, University Hospital Lausanne, Switzerland.
7 Institute of Pathology, University Bern, Bern, Switzerland.
8 Department of Nephrology, University Hospital Zurich, Zurich, Switzerland.
9 University Heart Centre, University Hospital Zurich, Zurich, Switzerland.
10 Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
Received 20 November 2017. Revision received 17 March 2018.
Accepted 11 April 2018.
S.E. received a travel grant from Sanofi-Genzyme and Shire. A.N. received lecturing honoraria, and research support from Sanofi Genzyme and Shire and received financial publication support for this article from Sanofi Genzyme. R.J.D. is a consultant to Alexion Pharmaceuticals, Amicus Therapeutics, Sanofi-Genzyme, and Sangamo Therapeutics, has founder shares of Amicus Therapeutics and options of Sangamo Therapeutics, and receives royalties from Sanofi-Genzyme and Shire HRT. F.B. received a research grant from Shire. The other authors have no conflicts of interests.
S.E. and A.N. participated in the research design, performance of the research, data analysis, and writing of the paper. U.H.D., S.C.K., F.B., and S.S. participated in the performance of the research, data analysis, and writing of the paper. R.J.D. and V.G. participated in data analysis and the writing of the paper. T.N., A.F., and M.C. participated in writing of the paper.
Correspondence: Albina Nowak, M.D., University Heart Centre, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland. (email@example.com).