Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 17;11(16):4810.
doi: 10.3390/jcm11164810.

Renoprotective Effect of Agalsidase Alfa: A Long-Term Follow-Up of Patients with Fabry Disease

Markus Cybulla  1 , Kathleen Nicholls  2   3 , Sandro Feriozzi  4 , Aleš Linhart  5 , Joan Torras  6   7 , Bojan Vujkovac  8 , Jaco Botha  9 , Christina Anagnostopoulou  9 , Michael L West  10 ; FOS Study Group
Affiliations

Renoprotective Effect of Agalsidase Alfa: A Long-Term Follow-Up of Patients with Fabry Disease

Markus Cybulla et al. J Clin Med. .

Abstract

Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, which, without treatment, can cause significant renal dysfunction. We evaluated the effects of enzyme replacement therapy with agalsidase alfa on renal decline in patients with Fabry disease using data from the Fabry Outcome Survey (FOS) registry. Male patients with Fabry disease aged >16 years at agalsidase alfa start were stratified by low (≤0.5 g/24 h) or high (>0.5 g/24 h) baseline proteinuria and by ‘classic’ or ‘non-classic’ phenotype. Overall, 193 male patients with low (n = 135) or high (n = 58) baseline proteinuria were evaluated. Compared with patients with low baseline proteinuria, those with high baseline proteinuria had a lower mean ± standard deviation baseline eGFR (89.1 ± 26.2 vs. 106.6 ± 21.8 mL/min/1.73 m2) and faster mean ± standard error eGFR decline (−3.62 ± 0.42 vs. −1.61 ± 0.28 mL/min/1.73 m2 per year; p < 0.0001). Patients with classic Fabry disease had similar rates of eGFR decline irrespective of baseline proteinuria; only one patient with non-classic Fabry disease had high baseline proteinuria, preventing meaningful comparisons between groups. In this analysis, baseline proteinuria significantly impacted the rate of eGFR decline in the overall population, suggesting that early treatment with good proteinuria control may be associated with renoprotective effects.

Keywords: Fabry disease; enzyme replacement therapy; estimated glomerular filtration rate; proteinuria.

PubMed Disclaimer

Conflict of interest statement

M Cybulla has served on advisory boards for Alexion, Amicus Therapeutics, and Takeda, has received honoraria from Amicus Therapeutics, Sanofi Genzyme, and Takeda, and travel expenses from Alexion, Amicus Therapeutics, and Takeda, outside the submitted work. K Nicholls has performed contracted research including clinical trials for Amicus Therapeutics, Avrobio, Idorsia, Protalix, Sanofi Genzyme, and Takeda, outside the submitted work, and has received honoraria from Amicus Therapeutics, Sanofi Genzyme, and Takeda. J Torras has served on advisory boards from Takeda, outside the submitted work. S Feriozzi reports personal fees from Amicus Therapeutics, Sanofi Genzyme, and Takeda, outside the submitted work. A Linhart reports personal fees from Amicus Therapeutics, Sanofi Genzyme, and Takeda, outside the submitted work. B Vujkovac reports personal fees from Amicus Therapeutics, Chiesi, Greenovation Biotech GmbH, Sanofi Genzyme, and Takeda, outside the submitted work. J Botha and C Anagnostopoulou are both employees of Takeda Pharmaceuticals International AG and stockholders of Takeda Pharmaceuticals Company Limited. M West has served on advisory boards for Amicus Therapeutics and Takeda; has received consulting fees from Amicus and Avrobio; has performed contracted research for Idorsia, Protalix, Sanofi Genzyme, and Takeda; and has served on speaker’s bureaus for Sanofi Genzyme and Takeda, outside the submitted work.

Figures

Figure 1
Figure 1
Change in eGFR over time by level of proteinuria at baseline. eGFR was measured using the CKD-EPI equation. CI—confidence interval; CKD-EPI—Chronic Kidney Disease Epidemiology Collaboration; eGFR—estimated glomerular filtration rate; SE, standard error.
Figure 2
Figure 2
Change in eGFR over time by mutation subgroup and level of proteinuria at baseline. (A) Classic mutations. (B) Non-classic mutations. eGFR was measured using the CKD-EPI equation. CI—confidence internal; CKD-EPI—Chronic Kidney Disease Epidemiology Collaboration; eGFR—estimated glomerular filtration rate; SE—standard error.
See this image and copyright information in PMC

References

    1. Mehta A., Clarke J.T.R., Giugliani R., Elliott P., Linhart A., Beck M., Sunder-Plassmann G. Natural course of Fabry disease: Changing pattern of causes of death in FOS–Fabry Outcome Survey. J. Med. Genet. 2009;46:548–552. doi: 10.1136/jmg.2008.065904. - DOI - PubMed
    1. Mehta A., Ricci R., Widmer U., Dehout F., Garcia de Lorenzo A., Kampmann C., Linhart A., Sunder-Plassmann G., Ries M., Beck M. Fabry disease defined: Baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur. J. Clin. Investig. 2004;34:236–242. doi: 10.1111/j.1365-2362.2004.01309.x. - DOI - PubMed
    1. Arends M., Wanner C., Hughes D., Mehta A., Oder D., Watkinson O.T., Elliott P.M., Linthorst G.E., Wijburg F.A., Biegstraaten M., et al. Characterization of classical and nonclassical Fabry disease: A multicenter study. J. Am. Soc. Nephrol. 2017;28:1631–1641. doi: 10.1681/ASN.2016090964. - DOI - PMC - PubMed
    1. Parini R., Pintos-Morell G., Hennermann J.B., Hsu T.R., Karabul N., Kalampoki V., Gurevich A., Ramaswami U., FOS Study Group Analysis of renal and cardiac outcomes in male participants in the Fabry Outcome Survey starting agalsidase alfa enzyme replacement therapy before and after 18 years of age. Drug Des. Dev. Ther. 2020;14:2149–2158. doi: 10.2147/DDDT.S249433. - DOI - PMC - PubMed
    1. Ramaswami U., Beck M., Hughes D., Kampmann C., Botha J., Pintos-Morell G., West M.L., Niu D.M., Nicholls K., Giugliani R., et al. Cardio-renal outcomes with long-term agalsidase alfa enzyme replacement therapy: A 10-year Fabry Outcome Survey (FOS) analysis. Drug Des. Dev. Ther. 2019;13:3705–3715. doi: 10.2147/DDDT.S207856. - DOI - PMC - PubMed