{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:57:27Z","timestamp":1784948247428,"version":"3.55.0"},"reference-count":57,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 BX004024"],"award-info":[{"award-number":["I01 BX004024"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000850","name":"National Heart and Lung Institute","doi-asserted-by":"publisher","award":["R35 HL135749"],"award-info":[{"award-number":["R35 HL135749"]}],"id":[{"id":"10.13039\/501100000850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000850","name":"National Heart and Lung Institute","doi-asserted-by":"publisher","award":["P01 HL116264"],"award-info":[{"award-number":["P01 HL116264"]}],"id":[{"id":"10.13039\/501100000850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK 020595"],"award-info":[{"award-number":["DK 020595"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK105160"],"award-info":[{"award-number":["DK105160"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001440","name":"ADA Foundation","doi-asserted-by":"publisher","award":["1-15-BS-172"],"award-info":[{"award-number":["1-15-BS-172"]}],"id":[{"id":"10.13039\/100001440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005384","name":"American Physiological Society","doi-asserted-by":"publisher","award":["Research Career Enhancement Award"],"award-info":[{"award-number":["Research Career Enhancement Award"]}],"id":[{"id":"10.13039\/100005384","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32 HL134643"],"award-info":[{"award-number":["T32 HL134643"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:p>Diabetic kidney disease (DKD) is one of the leading pathological causes of decreased renal function and progression to end-stage kidney failure. To explore and characterize age-related changes in DKD and associated glomerular damage, we used a rat model of type 2 diabetic nephropathy (T2DN) at 12 wk and older than 48 wk. We compared their disease progression with control nondiabetic Wistar and diabetic Goto-Kakizaki (GK) rats. During the early stages of DKD, T2DN and GK animals revealed significant increases in blood glucose and kidney-to-body weight ratio. Both diabetic groups had significantly altered renin-angiotensin-aldosterone system function. Thereafter, during the later stages of disease progression, T2DN rats demonstrated a remarkable increase in renal damage compared with GK and Wistar rats, as indicated by renal hypertrophy, polyuria accompanied by a decrease in urine osmolarity, high cholesterol, a significant prevalence of medullary protein casts, and severe forms of glomerular injury. Urinary nephrin shedding indicated loss of the glomerular slit diaphragm, which also correlates with the dramatic elevation in albuminuria and loss of podocin staining in aged T2DN rats. Furthermore, we used scanning ion microscopy topographical analyses to detect and quantify the pathological remodeling in podocyte foot projections of isolated glomeruli from T2DN animals. In summary, T2DN rats developed renal and physiological abnormalities similar to clinical observations in human patients with DKD, including progressive glomerular damage and a significant decrease in renin-angiotensin-aldosterone system plasma levels, indicating these rats are an excellent model for studying the progression of renal damage in type 2 DKD.<\/jats:p>","DOI":"10.1152\/ajprenal.00246.2019","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T14:24:06Z","timestamp":1569853446000},"page":"F1450-F1461","source":"Crossref","is-referenced-by-count":53,"title":["Progression of diabetic kidney disease in T2DN rats"],"prefix":"10.1152","volume":"317","author":[{"given":"Oleg","family":"Palygin","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisha","family":"Spires","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav","family":"Levchenko","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan","family":"Bohovyk","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykhailo","family":"Fedoriuk","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0812-824X","authenticated-orcid":false,"given":"Christine A.","family":"Klemens","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Sykes","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4411-3643","authenticated-orcid":false,"given":"John D.","family":"Bukowy","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Allen W.","family":"Cowley","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozef","family":"Lazar","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria V.","family":"Ilatovskaya","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5190-8356","authenticated-orcid":false,"given":"Alexander","family":"Staruschenko","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin"},{"name":"Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11491116"},{"key":"B2","first-page":"8","volume":"11","author":"Anguiano L","year":"2019","journal-title":"ASN Kidney News"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/1470320317705232"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70208-0"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00636.x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00353.x"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40639-x"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009070721"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017111210"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11111016"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/jcm4050998"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2012.07.011"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.07505.x"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/srep26428"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.119.85"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.01.006"},{"key":"B17","first-page":"598","volume":"106","author":"Kasiske BL","year":"1985","journal-title":"J Lab Clin Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2337\/diab.41.11.1422"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2147\/IJNRD.S103784"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4172\/2155-6156.S9-005"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.203869"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00320.x"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2018.02.003"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00143.2018"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet1066"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.3.735"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1306"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)62459-4"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.92331"},{"key":"B31","volume-title":"Kidney Disease in Diabetes","author":"Pavkov ME","year":"2018"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/428950"},{"key":"B34","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1681\/ASN.V10112382","volume":"10","author":"Price DA","year":"1999","journal-title":"J Am Soc Nephrol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1984.147"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4654-7"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1994.52"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042167"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13639"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004110970"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00234.2006"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-016-0167-x"},{"key":"B43","first-page":"624","volume":"4","author":"Sengupta P","year":"2013","journal-title":"Int J Prev Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.327866"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00155.2018"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00182.2018"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010010010"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.2174\/157339905774574374"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016060666"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1296"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c100049"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00941.x"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3525-8"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.028268"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2014.919907"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00262.2010"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006070798"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00246.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T11:41:04Z","timestamp":1664538064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00246.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,1]]},"references-count":57,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,12,1]]}},"alternative-id":["10.1152\/ajprenal.00246.2019"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00246.2019","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,1]]}}}