{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:28:28Z","timestamp":1790155708619,"version":"4.0.1"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2017,9]]},"abstract":"\n Background and objectives<\/jats:title>\n Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years.<\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7\u201362) years old. Agalsidase-\n \u03b1<\/jats:italic>\n or -\n \u03b2<\/jats:italic>\n was prescribed for a median of 9.4 (range =5\u201314) years. The lower fixed dose group received agalsidase 0.2 mg\/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2\u20131.0 mg\/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase-\n \u03b2<\/jats:italic>\n shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (\u22121.39 [SD=1.04];\n P<\/jats:italic>\n =0.004) and the higher dose group (\u22123.16 [SD=2.39];\n P<\/jats:italic>\n =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose (\n r<\/jats:italic>\n =0.69;\n P<\/jats:italic>\n =0.001). Arterial\/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions (\n P<\/jats:italic>\n =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol\/L [SD=11.9]) compared with the higher dose group (10.4 nmol\/L [SD=8.4]) and correlated with cumulative agalsidase dose in men (\n r<\/jats:italic>\n =0.71;\n P<\/jats:italic>\n =0.01).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial\/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.01820217","type":"journal-article","created":{"date-parts":[[2017,6,16]],"date-time":"2017-06-16T20:20:09Z","timestamp":1497644409000},"page":"1470-1479","source":"Crossref","is-referenced-by-count":54,"title":["Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease"],"prefix":"10.2215","volume":"12","author":[{"given":"Rannveig","family":"Skrunes","sequence":"first","affiliation":[{"name":"Medicine,"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen, Norway; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"T\u00f8ndel","sequence":"additional","affiliation":[{"name":"Pediatrics,"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen, Norway; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Leh","sequence":"additional","affiliation":[{"name":"Pathology, and"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen, Norway; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin Kampevold","family":"Larsen","sequence":"additional","affiliation":[{"name":"Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Houge","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einar Skulstad","family":"Davidsen","sequence":"additional","affiliation":[{"name":"Heart Disease and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Hollak","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism and"},{"name":"Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 B.P.","family":"van Kuilenburg","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric M.","family":"Vaz","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einar","family":"Svarstad","sequence":"additional","affiliation":[{"name":"Medicine,"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen, Norway; 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disease.","volume":"345","author":"Eng","year":"2001","journal-title":"N Engl J Med"},{"key":"B5-20230813","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1001\/jama.285.21.2743","article-title":"Enzyme replacement therapy in Fabry disease: A randomized controlled trial.","volume":"285","author":"Schiffmann","year":"2001","journal-title":"JAMA"},{"key":"B6-20230813","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s10038-005-0342-9","article-title":"Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice.","volume":"51","author":"Sakuraba","year":"2006","journal-title":"J Hum Genet"},{"key":"B7-20230813","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/glycob\/cwg034","article-title":"A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry 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Anderson-Fabry disease?","volume":"72","author":"Basic-Jukic","year":"2009","journal-title":"Med Hypotheses"}],"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01277230-201709000-00013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:36:54Z","timestamp":1786369014000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01277230-201709000-00013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,16]]},"references-count":40,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.2215\/cjn.01820217","relation":{},"ISSN":["1555-9041","1555-905X"],"issn-type":[{"value":"1555-9041","type":"print"},{"value":"1555-905X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,16]]}}}