{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:18:45Z","timestamp":1791919125238,"version":"4.3.4"},"reference-count":85,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T00:00:00Z","timestamp":1547769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["AR 1092\/2-1"],"award-info":[{"award-number":["AR 1092\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sodium retention and extracellular volume expansion are typical features of patients with nephrotic syndrome. In recent years, from in vitro data, endoluminal activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases has been proposed as an underlying mechanism. Recently, this concept was supported in vivo in nephrotic mice that were protected from proteolytic ENaC activation and sodium retention by the use of aprotinin for the pharmacological inhibition of urinary serine protease activity. These and other findings from studies in both rodents and humans highlight the impact of active proteases in the urine, or proteasuria, on ENaC\u2010mediated sodium retention and edema formation in nephrotic syndrome. Targeting proteasuria could become a therapeutic approach to treat patients with nephrotic syndrome. However, pathophysiologically relevant proteases remain to be identified. In this review, we introduce the concept of proteasuria to explain tubular sodium avidity and conclude that proteasuria can be considered as a key mechanism of sodium retention in patients with nephrotic syndrome.<\/jats:p>","DOI":"10.1111\/apha.13249","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T22:45:07Z","timestamp":1546296307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Proteasuria\u2014The impact of active urinary proteases on sodium retention in nephrotic syndrome"],"prefix":"10.1111","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3777-9316","authenticated-orcid":false,"given":"Ferruh","family":"Artunc","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry University Hospital T\u00fcbingen T\u00fcbingen Germany"},{"name":"Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University T\u00fcbingen T\u00fcbingen Germany"},{"name":"German Center for Diabetes Research (DZD) at the University T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"W\u00f6rn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry University Hospital T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Schork","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry University Hospital T\u00fcbingen T\u00fcbingen Germany"},{"name":"Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University T\u00fcbingen T\u00fcbingen Germany"},{"name":"German Center for Diabetes Research (DZD) at the University T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard N.","family":"Bohnert","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry University Hospital T\u00fcbingen T\u00fcbingen Germany"},{"name":"Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University T\u00fcbingen T\u00fcbingen Germany"},{"name":"German Center for Diabetes Research (DZD) at the University T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,18]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2435-6"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198810273191705"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-191711000-00002"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006111302"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-91-5-688"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(84)80021-9"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(79)90782-4"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000182827"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00032.2008"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000368491"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.07.023"},{"key":"e_1_2_14_13_1","first-page":"e57642","article-title":"Induction of nephrotic syndrome in mice by retrobulbar injection of doxorubicin and prevention of volume retention by sustained release aprotinin","volume":"135","author":"Bohnert BN","year":"2018","journal-title":"J Vis Exp"},{"key":"e_1_2_14_14_1","article-title":"Adriamycin\u2010induced nephrotic syndrome in rats: sequence of pathologic events","volume":"46","author":"Bertani T","year":"1982","journal-title":"Lab Invest"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V123598"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00399.2005"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110756"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00277.2003"},{"key":"e_1_2_14_19_1","first-page":"1","article-title":"Regulation of epithelial Na channels by aldosterone","volume":"46","author":"Palmer LG","year":"2016","journal-title":"Kitasato Med J"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021317-121143"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.010908.163108"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R800083200"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2013.275"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400080200"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00157.2014"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00133.2012"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.154435"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00342.2003"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008040364"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805676200"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201110763"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e3283330fb2"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.180"},{"key":"e_1_2_14_34_1","first-page":"479","article-title":"Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs","volume":"33","author":"Fritz H","year":"1983","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2014.11.006"},{"key":"e_1_2_14_36_1","first-page":"P085","article-title":"Protease inhibitors in nephrotic urine may prevent proteolytic activation of the epithelial sodium channel (ENaC) by urinary proteases","volume":"694","author":"Nacken R","year":"2013","journal-title":"Acta Physiol Suppl"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2010.0360"},{"key":"e_1_2_14_38_1","first-page":"49","article-title":"Characterisation and quantification of proteasuria in nephrotic syndrome","volume":"6","author":"Artunc F","year":"2018","journal-title":"EMJ Nephrol"},{"key":"e_1_2_14_39_1","unstructured":"W\u00f6rnM AlenaziF KalbacherH HeyneN ArtuncF.Characterization and quantification of proteasuria in nephrotic syndrome. 9th Annual Meeting of the German Society of Nephrology.http:\/\/www.abstractserver.com\/publication\/nephro2017\/nephro2017Abstracts.PDF 2017."},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfy104.FP278"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-018-9183-3"},{"key":"e_1_2_14_42_1","unstructured":"W\u00f6rnM BoldtK UeffingM HeyneN ArtuncF.Identification of serine proteases in urine from patients with nephrotic syndrome using a proteomic approach. 10th Annual Meeting of the German Society of Nephrology https:\/\/www.abstractserver.com\/publication\/nephro2018\/ 2018."},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.198879"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfu402"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000216"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.12261115"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13060"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2439-2"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013111173"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005040363"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.ndt.a027137"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.19"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013030285"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-012-0286-3"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010121289"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-56827-0_3"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12651"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.09220.x"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.10360917"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2018.06.007"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/11.1.32"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00162.2016"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016101119"},{"key":"e_1_2_14_64_1","first-page":"93","article-title":"Amiloride\u2010sensitive and amiloride\u2010insensitive kaliuresis in advanced chronic kidney disease","volume":"21","author":"Levy Yeyati N","year":"2008","journal-title":"J Nephrol"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-0644(97)70078-7"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.1979.tb127002.x"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)92450-8"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.05.008"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13743"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/1559-0275-10-17"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051379"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1515\/bchm.1998.379.10.1271"},{"key":"e_1_2_14_73_1","unstructured":"W\u00f6rnerS BohnertBN DanielC AmannK ArtuncF.Renal effects of the serine protease inhibitor aprotinin in healthy mice.http:\/\/wwwabstractservercom\/publication\/nephro2017\/nephro2017AbstractsPDF 2017."},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01852177"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00586.2012"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00705.2011"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00706.2011"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e328317a762"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.1159\/000168295"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-6632(91)90060-3"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000967"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00138.2015"},{"key":"e_1_2_14_83_1","first-page":"208A","article-title":"Urokinase\u2010type plasminogen activator is not required for edema formation during experimental nephrotic syndrome","volume":"27","author":"Artunc F","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00015.2002"},{"key":"e_1_2_14_85_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.04390808"},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2007.10.040"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapha.13249","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.13249","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apha.13249","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.13249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T21:37:46Z","timestamp":1694381866000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.13249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,18]]},"references-count":85,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/apha.13249"],"URL":"https:\/\/doi.org\/10.1111\/apha.13249","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,18]]},"assertion":[{"value":"2018-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13249"}}