{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:15:46Z","timestamp":1790813746669,"version":"4.1.0"},"reference-count":116,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Nephrology"],"published-print":{"date-parts":[[2012]]},"abstract":"<jats:p>A large body of evidence indicates that proteinuria is a strong predictor of morbidity, a cause of inflammation, oxidative stress and progression of chronic kidney disease, and development of cardiovascular disease. The processes that lead to proteinuria are complex and involve factors such as glomerular hemodynamic, tubular absorption, and diffusion gradients. Alterations in various different molecular pathways and interactions may lead to the identical clinical end points of proteinuria and chronic kidney disease. Glomerular diseases include a wide range of immune and nonimmune insults that may target and thus damage some components of the glomerular filtration barrier. In many of these conditions, the renal visceral epithelial cell (podocyte) responds to injury along defined pathways, which may explain the resultant clinical and histological changes. The recent discovery of the molecular components of the slit diaphragm, specialized structure of podocyte-podocyte interaction, has been a major breakthrough in understanding the crucial role of the epithelial layer of the glomerular barrier and the pathogenesis of proteinuria. Thispaper provides an overview and update on the structure and function of the glomerular filtration barrier and the pathogenesis of proteinuria, highlighting the role of the podocyte in this setting. In addition, current antiproteinuric therapeutic approaches are briefly commented.<\/jats:p>","DOI":"10.1155\/2012\/546039","type":"journal-article","created":{"date-parts":[[2012,7,5]],"date-time":"2012-07-05T06:16:39Z","timestamp":1341468999000},"page":"1-13","source":"Crossref","is-referenced-by-count":57,"title":["Understanding the Mechanisms of Proteinuria: Therapeutic Implications"],"prefix":"10.1155","volume":"2012","author":[{"given":"Jorge E.","family":"Toblli","sequence":"first","affiliation":[{"name":"Laboratorio de Medicina Experimental, Hospital Alem\u00e1n, Facultad de Medicina, University of Buenos Aires, Avenida Pueyrredon 1640, 1118 Buenos Aires, Argentina"},{"name":"Servicio de Nefrolog\u00eda, Hospital Alem\u00e1n, 1118 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Bevione","sequence":"additional","affiliation":[{"name":"Servicio de Nefrolog\u00eda, Hospital Alem\u00e1n, 1118 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Di Gennaro","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Interna, Hospital Alem\u00e1n, 1118 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Madalena","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Experimental, Hospital Alem\u00e1n, Facultad de Medicina, University of Buenos Aires, Avenida Pueyrredon 1640, 1118 Buenos Aires, Argentina"},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, 1113 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Cao","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Experimental, Hospital Alem\u00e1n, Facultad de Medicina, University of Buenos Aires, Avenida Pueyrredon 1640, 1118 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Angerosa","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Experimental, Hospital Alem\u00e1n, Facultad de Medicina, University of Buenos Aires, Avenida Pueyrredon 1640, 1118 Buenos Aires, Argentina"},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, 1113 Buenos Aires, Argentina"},{"name":"Hospital de Clinicas \u201cJos\u00e9 de San Mart\u00edn\u201d, Universidad de Buenos Aires, 1120 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"98","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.09741110"},{"issue":"4","key":"2","first-page":"375","volume":"20","year":"2007","journal-title":"Journal of Nephrology"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2009.04.029"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.39"},{"issue":"2","key":"5","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1053\/ajkd.2000.8996","volume":"36","year":"2000","journal-title":"American Journal of Kidney Diseases"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000031732.78052.81"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000133312.96477.48"},{"issue":"8","key":"8","doi-asserted-by":"crossref","first-page":"629","DOI":"10.7326\/0003-4819-134-8-200104170-00007","volume":"134","year":"2001","journal-title":"Annals of Internal Medicine"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2011.03.002"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.424"},{"issue":"5","key":"11","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s004240000307","volume":"440","year":"2000","journal-title":"Pflugers Archiv European Journal of Physiology"},{"issue":"1","key":"12","doi-asserted-by":"crossref","first-page":"F1","DOI":"10.1152\/ajpcell.1994.266.1.C1","volume":"266","year":"1994","journal-title":"American Journal of Physiology"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007111205"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00173.2005"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1159\/000101798"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707330"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90601.2008"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1159\/000209209"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1159\/000046320"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/13.10.2519"},{"issue":"10","key":"21","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1136\/jcp.52.10.735","volume":"52","year":"1999","journal-title":"Journal of Clinical Pathology"},{"issue":"4","key":"22","first-page":"269","volume":"55","year":"2001","journal-title":"Clinical Nephrology"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq200"},{"issue":"4","key":"24","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1053\/j.ajkd.2011.05.032","volume":"58","year":"2011","journal-title":"American Journal of Kidney Diseases"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-011-1785-1"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022296"},{"issue":"23","key":"27","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1101\/gad.10.23.2981","volume":"10","year":"1996","journal-title":"Genes and Development"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002706"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30894"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200603073"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006010033"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005090921"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.137"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1159\/000320878"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008070782"},{"issue":"4","key":"36","first-page":"805","volume":"141","year":"1992","journal-title":"American Journal of Pathology"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1080\/10715760601064706"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002469"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008101117"},{"issue":"1","key":"40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/hmg\/10.1.1","volume":"10","year":"2001","journal-title":"Human Molecular Genetics"},{"issue":"3","key":"41","doi-asserted-by":"crossref","first-page":"807","DOI":"10.4049\/jimmunol.141.3.807","volume":"141","year":"1988","journal-title":"Journal of Immunology"},{"issue":"6","key":"42","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1016\/S0002-9440(10)63590-0","volume":"163","year":"2003","journal-title":"American Journal of Pathology"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.381"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301279200"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422562C1"},{"issue":"2","key":"46","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1128\/MCB.24.2.550-560.2004","volume":"24","year":"2004","journal-title":"Molecular and Cellular Biology"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00202.x"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(02)00527-2"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00268.2005"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00185.2007"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106215"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006091010"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.06.033"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.466"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1177\/1933719109338630"},{"issue":"4","key":"56","first-page":"1141","volume":"151","year":"1997","journal-title":"American Journal of Pathology"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.080063"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e3283520f38"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00636-6"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.135"},{"key":"61","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfm191"},{"key":"62","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004030180"},{"key":"63","doi-asserted-by":"publisher","DOI":"10.1159\/000103918"},{"key":"64","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.43"},{"key":"65","doi-asserted-by":"publisher","DOI":"10.1159\/000106782"},{"key":"66","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008091005"},{"key":"67","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp367"},{"key":"68","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011070690"},{"key":"69","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39492"},{"key":"70","doi-asserted-by":"publisher","DOI":"10.1038\/nature06639"},{"key":"71","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.11.005"},{"key":"74","doi-asserted-by":"publisher","DOI":"10.1038\/ng.232"},{"key":"75","doi-asserted-by":"publisher","DOI":"10.1038\/ng.226"},{"key":"76","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.08721209"},{"key":"77","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193032"},{"key":"78","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.251"},{"key":"79","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-010-0861-0"},{"key":"80","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011010069"},{"issue":"8","key":"81","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.4161\/auto.7066","volume":"4","year":"2008","journal-title":"Autophagy"},{"key":"121","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-010-1115-0"},{"issue":"4","key":"84","first-page":"599","volume":"57","year":"2006","journal-title":"Journal of Physiology and Pharmacology"},{"issue":"1","key":"85","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1152\/physrev.00020.2002","volume":"83","year":"2003","journal-title":"Physiological Reviews"},{"key":"86","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2005.04203.x"},{"issue":"12","key":"87","first-page":"1151","volume":"9","year":"1991","journal-title":"Journal of Hypertension"},{"issue":"15","key":"88","doi-asserted-by":"crossref","first-page":"11628","DOI":"10.1016\/S0021-9258(19)78171-X","volume":"269","year":"1994","journal-title":"The Journal of Biological Chemistry"},{"key":"89","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(98)00278-1"},{"issue":"2","key":"90","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/ki.1991.199","volume":"40","year":"1991","journal-title":"Kidney International"},{"key":"91","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.10.013"},{"key":"92","doi-asserted-by":"publisher","DOI":"10.1159\/000066790"},{"issue":"4","key":"93","first-page":"F601","volume":"263","year":"1992","journal-title":"American Journal of Physiology"},{"key":"94","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002041"},{"issue":"3","key":"95","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1681\/ASN.2011070666","volume":"23","year":"2012","journal-title":"Journal of the American Society of Nephrology"},{"key":"97","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000141"},{"issue":"3","key":"98","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1172\/JCI111270","volume":"73","year":"1984","journal-title":"Journal of Clinical Investigation"},{"key":"99","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90638.2008"},{"key":"100","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007090997"},{"key":"101","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006111266"},{"key":"102","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-009-1381-9"},{"issue":"4","key":"103","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1159\/000045419","volume":"83","year":"1999","journal-title":"Nephron"},{"key":"104","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000039569.34360.5E"},{"issue":"4","key":"105","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1681\/ASN.V114669","volume":"11","year":"2000","journal-title":"Journal of the American Society of Nephrology"},{"issue":"12","key":"106","first-page":"1599","volume":"26","year":"2011","journal-title":"Histology and Histopathology"},{"key":"107","doi-asserted-by":"publisher","DOI":"10.2174\/157339908783502370"},{"key":"108","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)10363-X"},{"key":"109","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011303"},{"key":"110","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011161"},{"key":"111","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199604113341502"},{"key":"112","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00661.x"},{"key":"113","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0708379"},{"key":"114","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009070737"},{"key":"115","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.00240106"},{"issue":"5","key":"116","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1681\/ASN.V125993","volume":"12","year":"2001","journal-title":"Journal of the American Society of Nephrology"},{"key":"117","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes."},{"key":"118","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006010064"},{"key":"119","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00058.2011"},{"key":"120","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2010.130"}],"container-title":["International Journal of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijn\/2012\/546039.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijn\/2012\/546039.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijn\/2012\/546039.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T02:12:28Z","timestamp":1687572748000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/ijn\/2012\/546039\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012]]},"references-count":116,"alternative-id":["546039","546039"],"URL":"https:\/\/doi.org\/10.1155\/2012\/546039","relation":{},"ISSN":["2090-214X","2090-2158"],"issn-type":[{"value":"2090-214X","type":"print"},{"value":"2090-2158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012]]}}}