{"doi":"10.2215/cjn.01820217","title":"Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease","abstract":"<jats:sec>\n            <jats:title>Background and objectives</jats:title>\n            <jats:p>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          <jats:sec>\n            <jats:title>Design, setting, participants, &amp; measurements</jats:title>\n            <jats:p>Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7–62) years old. Agalsidase-<jats:italic toggle=\"yes\">α</jats:italic> or -<jats:italic toggle=\"yes\">β</jats:italic> was prescribed for a median of 9.4 (range =5–14) 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 (0.2–1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase-<jats:italic toggle=\"yes\">β</jats:italic> 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.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Results</jats:title>\n            <jats:p>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 (−1.39 [SD=1.04]; <jats:italic toggle=\"yes\">P</jats:italic>=0.004) and the higher dose group (−3.16 [SD=2.39]; <jats:italic toggle=\"yes\">P</jats:italic>=0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose (<jats:italic toggle=\"yes\">r</jats:italic>=0.69; <jats:italic toggle=\"yes\">P</jats:italic>=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 (<jats:italic toggle=\"yes\">P</jats:italic>=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 (<jats:italic toggle=\"yes\">r</jats:italic>=0.71; <jats:italic toggle=\"yes\">P</jats:italic>=0.01).</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions</jats:title>\n            <jats:p>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>","journal":"Clinical Journal of the American Society of Nephrology","year":2017,"id":16506,"datarank":3.1231885914442463,"base_score":4.110873864173311,"endowment":4.110873864173311,"self_citation_contribution":0.6166310796259968,"citation_network_contribution":2.5065575118182495,"self_endowment_contribution":0.6166310796259968,"citer_contribution":2.5065575118182495,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":53,"citers_with_citation_signal":48,"citers_with_endowment":48,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":121581,"name":"Camilla Tøndel","orcid":null,"position":1,"is_corresponding":false},{"id":121582,"name":"Sabine Leh","orcid":null,"position":2,"is_corresponding":false},{"id":121583,"name":"Kristin Kampevold Larsen","orcid":null,"position":3,"is_corresponding":false},{"id":121584,"name":"Gunnar Houge","orcid":null,"position":4,"is_corresponding":false},{"id":121585,"name":"Einar Skulstad Davidsen","orcid":null,"position":5,"is_corresponding":false},{"id":121586,"name":"Carla Hollak","orcid":null,"position":6,"is_corresponding":false},{"id":121587,"name":"André B.P. van Kuilenburg","orcid":null,"position":7,"is_corresponding":false},{"id":121588,"name":"Frédéric M. Vaz","orcid":null,"position":8,"is_corresponding":false},{"id":121589,"name":"Einar Svarstad","orcid":null,"position":9,"is_corresponding":false},{"id":121580,"name":"Rannveig Skrunes","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.110873864173311,"endowment":4.110873864173311,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28625968","pmcid":"PMC5586567","openalex_id":"https://openalex.org/W2624878463","authors":[],"funders":[],"total_grants":0,"fwci":3.4628,"citation_percentile":0.92886012,"influential_citations":2,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":6},{"year":2019,"count":1},{"year":2020,"count":14},{"year":2021,"count":9},{"year":2022,"count":12},{"year":2023,"count":5},{"year":2024,"count":4},{"year":2025,"count":8}],"oa_status":"bronze","license":"other-oa","oa_locations":[{"url":"https://cjasn.asnjournals.org/content/clinjasn/12/9/1470.full.pdf","host_type":"journal"},{"url":"https://cjasn.asnjournals.org/content/clinjasn/12/9/1470.full.pdf","host_type":"BRONZE"},{"url":"https://cjasn.asnjournals.org/content/clinjasn/12/9/1470.full.pdf","host_type":"publisher"},{"url":"https://journals.lww.com/01277230-201709000-00013","host_type":"publisher"},{"url":"https://doi.org/10.2215/cjn.01820217","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28625968","host_type":"repository"},{"url":"https://pure.amsterdamumc.nl/en/publications/11006918-64fd-4f64-920c-fb25bc64b873","host_type":"repository"},{"url":"https://pure.amc.nl/en/publications/longterm-dosedependent-agalsidase-effects-on-kidney-histology-in-fabry-disease(1a034f43-8f85-4e03-a643-feeec6748db6).html","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5586567","host_type":"repository"},{"url":"https://pure.amsterdamumc.nl/ws/files/159032308/Long-term-dose-dependent-agalsidase-effects-on-kidney-histology-in-fabry-disease.pdf","host_type":"repository"}],"fields_of_study":["Lysosomal Storage Disorders Research","Renal Diseases and Glomerulopathies","Biomedical Research and Pathophysiology","Medicine","Adolescent","Adult","Biopsy","Child","Dose-Response Relationship, Drug","Drug Administration Schedule","Enzyme Replacement Therapy","Fabry Disease","Female","Glomerular Filtration Rate","Humans","Isoenzymes","Kidney","Male","Middle Aged","Norway","Time Factors","Treatment Outcome","Trihexosylceramides","Young Adult","alpha-Galactosidase"],"mesh_terms":["Adolescent","Adult","alpha-Galactosidase","Fabry Disease","Biopsy","Child","Dose-Response Relationship, Drug","Drug Administration Schedule","Female","Glomerular Filtration Rate","Humans","Isoenzymes","Kidney","Male","Middle Aged","Norway","Time Factors","Trihexosylceramides","Treatment Outcome","Young Adult","Enzyme Replacement Therapy"],"keywords":["Medicine","Fabry disease","Histology","Kidney","Term (time)","Fabry's disease","Urology","Internal medicine","Disease","Isoenzymes","Male","Adult","Child","Biomarkers","Follow-up studies","Adolescent","Biopsy","glomerular filtration rate","Podocyte","Albuminuria","Middle aged","Chronic Kidney Disease","Podocytes","Humans","Young Adult","Disease Progression","Enzyme Replacement Therapy","Genetic Renal Disease","Trihexosylceramides","Alpha-galactosidas"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-02T09:47:30.883397Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}