{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:28:47Z","timestamp":1791379727344,"version":"4.3.3"},"reference-count":44,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,6,18]],"date-time":"2019-06-18T00:00:00Z","timestamp":1560816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MH"],"award-info":[{"award-number":["MH"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["kireports.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Kidney International Reports"],"published-print":{"date-parts":[[2019,10]]},"DOI":"10.1016\/j.ekir.2019.06.012","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T13:10:16Z","timestamp":1561468216000},"page":"1454-1462","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"title":["Rationale and Design for a Phase 1 Study of N-Acetylmannosamine for Primary Glomerular Diseases"],"prefix":"10.1016","volume":"4","author":[{"given":"Marjan","family":"Huizing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Yardeni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Fuentes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May C.V.","family":"Malicdan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petcharat","family":"Leoyklang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Volkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Dekel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Brede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi","family":"Blake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alva","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harish","family":"Chatrathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Anikster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Carrillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B.","family":"Kopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ekir.2019.06.012_bib1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/glycob\/2.1.25","article-title":"Diversity in the sialic acids","volume":"2","author":"Varki","year":"1992","journal-title":"Glycobiology"},{"key":"10.1016\/j.ekir.2019.06.012_bib2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.sbi.2009.06.003","article-title":"Sialic acids as regulators of molecular and cellular interactions","volume":"19","author":"Schauer","year":"2009","journal-title":"Curr Opin Struct Biol"},{"key":"10.1016\/j.ekir.2019.06.012_bib3","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1126\/science.284.5418.1372","article-title":"UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation","volume":"284","author":"Keppler","year":"1999","journal-title":"Science"},{"key":"10.1016\/j.ekir.2019.06.012_bib4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.molmed.2008.06.002","article-title":"Sialic acids in human health and disease","volume":"14","author":"Varki","year":"2008","journal-title":"Trends Mol Med"},{"key":"10.1016\/j.ekir.2019.06.012_bib5","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.3389\/fimmu.2017.01347","article-title":"Pro-inflammatory state in monoclonal gammopathy of undetermined significance and in multiple myeloma is characterized by low sialylation of pathogen-specific and other monoclonal immunoglobulins","volume":"8","author":"Bosseboeuf","year":"2017","journal-title":"Front Immunol"},{"key":"10.1016\/j.ekir.2019.06.012_bib6","doi-asserted-by":"crossref","first-page":"24313","DOI":"10.1074\/jbc.272.39.24313","article-title":"A\u00a0bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Purification and characterization of UDP-N-acetylglucosamine 2-epimerase\/N-acetylmannosamine kinase","volume":"272","author":"Hinderlich","year":"1997","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.ekir.2019.06.012_bib7","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ymgme.2017.04.010","article-title":"Safety, pharmacokinetics and sialic acid production after oral administration of N-acetylmannosamine (ManNAc) to subjects with GNE myopathy","volume":"122","author":"Xu","year":"2017","journal-title":"Mol Genet Metab"},{"key":"10.1016\/j.ekir.2019.06.012_bib8","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1073\/pnas.52.2.371","article-title":"The feedback control of sugar nucleotide biosynthesis in liver","volume":"52","author":"Kornfeld","year":"1964","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.ekir.2019.06.012_bib9","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1086\/302411","article-title":"Mutations in the human UDP-Nacetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme","volume":"64","author":"Seppala","year":"1999","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.ekir.2019.06.012_bib10","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0300-9084(01)01301-3","article-title":"The human sialyltransferase family","volume":"83","author":"Harduin-Lepers","year":"2001","journal-title":"Biochimie"},{"key":"10.1016\/j.ekir.2019.06.012_bib11","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s00253-012-4040-1","article-title":"Sialic acid metabolism and sialyltransferases: natural functions and applications","volume":"94","author":"Li","year":"2012","journal-title":"Appl Microbiol Biotechnol"},{"key":"10.1016\/j.ekir.2019.06.012_bib12","first-page":"477","article-title":"Glomerular sialic acid and proteinuria in human renal disease","volume":"28","author":"Blau","year":"1973","journal-title":"Lab Invest"},{"key":"10.1016\/j.ekir.2019.06.012_bib13","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S0344-0338(87)80103-6","article-title":"Ultrastructural alterations in the sialic acid distribution in minimal change disease and membranous glomerulonephritis","volume":"182","author":"Quatacker","year":"1987","journal-title":"Pathol Res Pract"},{"key":"10.1016\/j.ekir.2019.06.012_bib14","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1111\/j.1523-1755.2004.05407.x","article-title":"Aberrant glycosylation in IgA nephropathy (IgAN)","volume":"65","author":"Coppo","year":"2004","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2019.06.012_bib15","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/ki.2009.473","article-title":"Aberrantly glycosylated IgA1 induces mesangial cells to produce platelet-activating factor that mediates nephrin loss in cultured podocytes","volume":"77","author":"Coppo","year":"2010","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2019.06.012_bib16","first-page":"907","article-title":"In\u00a0vivo enzymatic removal of alpha 2,6-linked sialic acid from the glomerular filtration barrier results in podocyte charge alteration and glomerular injury","volume":"74","author":"Gelberg","year":"1996","journal-title":"Lab Invest"},{"key":"10.1016\/j.ekir.2019.06.012_bib17","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1172\/JCI30954","article-title":"Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine","volume":"117","author":"Galeano","year":"2007","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.ekir.2019.06.012_bib18","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1016\/j.ajpath.2011.12.023","article-title":"The Gne M712T mouse as a model for human glomerulopathy","volume":"180","author":"Kakani","year":"2012","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ekir.2019.06.012_bib19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0029873","article-title":"Glycoprotein hyposialylation gives rise to a nephrotic-like syndrome that is prevented by sialic acid administration in GNE V572L point-mutant mice","volume":"7","author":"Ito","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ekir.2019.06.012_bib20","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1681\/ASN.2011090947","article-title":"Deficits in sialylation impair podocyte maturation","volume":"23","author":"Weinhold","year":"2012","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2019.06.012_bib21","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.ymgme.2012.10.011","article-title":"Oral monosaccharide therapies to reverse renal and muscle hyposialylation in a mouse model of GNE myopathy","volume":"107","author":"Niethamer","year":"2012","journal-title":"Mol Genet Metab"},{"key":"10.1016\/j.ekir.2019.06.012_bib22","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1021\/bi00661a029","article-title":"Sialic acid uptake by fibroblasts","volume":"15","author":"Hirschberg","year":"1976","journal-title":"Biochemistry"},{"key":"10.1016\/j.ekir.2019.06.012_bib23","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/bit.10901","article-title":"Characterization of the cellular uptake and metabolic conversion of acetylated N-acetylmannosamine (ManNAc) analogues to sialic acids","volume":"85","author":"Jones","year":"2004","journal-title":"Biotechnol Bioeng"},{"key":"10.1016\/j.ekir.2019.06.012_bib24","doi-asserted-by":"crossref","first-page":"4228","DOI":"10.1074\/jbc.M412040200","article-title":"Mechanism of uptake and incorporation of the non-human sialic acid N-glycolylneuraminic acid into human cells","volume":"280","author":"Bardor","year":"2005","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.ekir.2019.06.012_bib25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0167-4889(85)90107-7","article-title":"Accumulation of N-acetylneuraminic acid (sialic acid) in human fibroblasts cultured in the presence of N-acetylmannosamine","volume":"846","author":"Thomas","year":"1985","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.ekir.2019.06.012_bib26","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1002\/(SICI)1097-0290(19980620)58:6<642::AID-BIT10>3.0.CO;2-9","article-title":"Improvement of interferon-gamma sialylation in Chinese hamster ovary cell culture by feeding of N-acetylmannosamine","volume":"58","author":"Gu","year":"1998","journal-title":"Biotechnol Bioeng"},{"key":"10.1016\/j.ekir.2019.06.012_bib27","doi-asserted-by":"crossref","first-page":"5079","DOI":"10.1016\/j.febslet.2005.08.013","article-title":"The intracellular concentration of sialic acid regulates the polysialylation of the neural cell adhesion molecule","volume":"579","author":"Bork","year":"2005","journal-title":"FEBS Lett"},{"key":"10.1016\/j.ekir.2019.06.012_bib28","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201800186","article-title":"Combining butyrated ManNAc with glycoengineered CHO cells improves EPO glycan quality and production","volume":"14","author":"Wang","year":"2019","journal-title":"Biotechnol J"},{"key":"10.1016\/j.ekir.2019.06.012_bib29","doi-asserted-by":"crossref","first-page":"9255","DOI":"10.1074\/jbc.M111619200","article-title":"Differential effects of unnatural sialic acids on the polysialylation of the neural cell adhesion molecule and neuronal behavior","volume":"277","author":"Charter","year":"2002","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.ekir.2019.06.012_bib30","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12014-015-9083-8","article-title":"Identification of sialylated glycoproteins from metabolically oligosaccharide engineered pancreatic cells","volume":"12","author":"Tian","year":"2015","journal-title":"Clin Proteomics"},{"key":"10.1016\/j.ekir.2019.06.012_bib31","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/labinvest.2015.78","article-title":"Sialic acid supplementation ameliorates puromycin aminonucleoside nephrosis in rats","volume":"95","author":"Pawluczyk","year":"2015","journal-title":"Lab Invest"},{"key":"10.1016\/j.ekir.2019.06.012_bib32","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nm.2261","article-title":"Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome","volume":"17","author":"Clement","year":"2011","journal-title":"Nat Med"},{"key":"10.1016\/j.ekir.2019.06.012_bib33","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/ng718","article-title":"The UDP-N-acetylglucosamine 2-epimerase\/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy","volume":"29","author":"Eisenberg","year":"2001","journal-title":"Nature Genet"},{"key":"10.1016\/j.ekir.2019.06.012_bib34","series-title":"The Online Metabolic and Molecular Bases of Inherited Disease","article-title":"GNE myopathy","author":"Huizing","year":"2014"},{"key":"10.1016\/j.ekir.2019.06.012_bib35","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1007\/s13311-018-0671-y","article-title":"GNE myopathy: etiology, diagnosis, and therapeutic challenges","volume":"15","author":"Carrillo","year":"2018","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.ekir.2019.06.012_bib36","first-page":"49","article-title":"Aceneuramic acid extended release administration maintains upper limb muscle strength in a 48-week study of subjects with GNE myopathy: results from a phase 2, randomized, controlled study","volume":"3","author":"Argov","year":"2016","journal-title":"J\u00a0Neuromuscul Dis"},{"key":"10.1016\/j.ekir.2019.06.012_bib37","doi-asserted-by":"crossref","first-page":"11751","DOI":"10.1073\/pnas.95.20.11751","article-title":"A\u00a0mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence","volume":"95","author":"Chou","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ekir.2019.06.012_bib38","doi-asserted-by":"crossref","first-page":"15708","DOI":"10.1074\/jbc.272.25.15708","article-title":"Molecular cloning and characterization of human podocalyxin-like protein. Orthologous relationship to rabbit PCLP1 and rat podocalyxin","volume":"272","author":"Kershaw","year":"1997","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.ekir.2019.06.012_bib39","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1074\/JBC.X600004200","article-title":"Lectins: carbohydrate-specific reagents and biological recognition molecules","volume":"282","author":"Sharon","year":"2007","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.ekir.2019.06.012_bib40","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ab.2008.12.005","article-title":"Specificity analysis of lectins and antibodies using remodeled glycoproteins","volume":"386","author":"Iskratsch","year":"2009","journal-title":"Anal Biochem"},{"key":"10.1016\/j.ekir.2019.06.012_bib41","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1172\/JCI32482","article-title":"Sizing up sialic acid inglomerular disease","volume":"117","author":"Quaggin","year":"2007","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.ekir.2019.06.012_bib42","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1053\/j.ajkd.2011.05.019","article-title":"Expressing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) cystatin C equations for estimating GFR with standardized serum cystatin C values","volume":"58","author":"Inker","year":"2011","journal-title":"Am J Kidney Dis"},{"key":"10.1016\/j.ekir.2019.06.012_bib43","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jchromb.2015.07.018","article-title":"Quantitative hydrophilic interaction chromatography-mass spectrometry analysis of N-acetylneuraminic acid and N-acetylmannosamine in human plasma","volume":"1000","author":"Shi","year":"2015","journal-title":"J\u00a0Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"10.1016\/j.ekir.2019.06.012_bib44","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.kint.2018.11.007","article-title":"Burden, access, and disparities in kidney disease","volume":"95","author":"Crews","year":"2019","journal-title":"Kidney Int"}],"container-title":["Kidney International Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2468024919313956?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2468024919313956?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T03:25:34Z","timestamp":1762831534000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2468024919313956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["S2468024919313956"],"URL":"https:\/\/doi.org\/10.1016\/j.ekir.2019.06.012","relation":{},"ISSN":["2468-0249"],"issn-type":[{"value":"2468-0249","type":"print"}],"subject":[],"published":{"date-parts":[[2019,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Rationale and Design for a Phase 1 Study of N-Acetylmannosamine for Primary Glomerular Diseases","name":"articletitle","label":"Article Title"},{"value":"Kidney International Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ekir.2019.06.012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc. on behalf of the International Society of Nephrology.","name":"copyright","label":"Copyright"}]}}