{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:17:40Z","timestamp":1791407860887,"version":"4.3.3"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN 119368"],"award-info":[{"award-number":["FRN 119368"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000191","name":"Kidney Foundation of Canada","doi-asserted-by":"publisher","award":["KFOC120010"],"award-info":[{"award-number":["KFOC120010"]}],"id":[{"id":"10.13039\/501100000191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>The use of animal models to predict the response to new therapies in humans is a vexing issue in nephrology. Unlike patients with chronic kidney disease (CKD), few rodent models develop a progressive decline in glomerular filtration rate (GFR) so that experimental studies frequently report a reduction in proteinuria as the primary efficacy outcome. Moreover, while humans present with established kidney disease that continues to progress, many experimental studies investigate therapies in the prevention rather than in a therapeutic setting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used the remnant kidney (subtotal nephrectomy [SNX]) rat model that develops a decline in GFR in conjunction with heavy proteinuria and hypertension along with the histological hallmarks of CKD in humans, glomerulosclerosis and tubulointerstitial fibrosis. Using agents that had been shown to improve GFR as well as proteinuria in the prevention setting, angiotensin\u2010converting enzyme (ACE) inhibition with enalapril and SIRT1 activation with SRT3025, treatment was initiated 6\u2009weeks after SNX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While enalapril reduced blood pressure, proteinuria and histological injury, it did not improve GFR, as measured by inulin clearance. SRT3025 improved neither GFR nor structural damage despite a reduction in proteinuria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings demonstrate that neither a reduction in proteinuria nor a reversal of structural damage in the kidney will necessarily translate to a restoration of kidney function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nep.13828","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T11:50:58Z","timestamp":1605181858000},"page":"270-279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Late intervention in the remnant kidney model attenuates proteinuria but not glomerular filtration rate decline"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6555-2899","authenticated-orcid":false,"given":"Matthew R.","family":"Veitch","sequence":"first","affiliation":[{"name":"Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital  Toronto Ontario Canada"},{"name":"Faculty of Medicine, Department of Laboratory Medicine &amp; Pathobiology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri","family":"Thai","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Francois","family":"Desjardins","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Golam","family":"Kabir","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim A.","family":"Connelly","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital  Toronto Ontario Canada"},{"name":"Faculty of Medicine, Department of Laboratory Medicine &amp; Pathobiology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital  Toronto Ontario Canada"},{"name":"Faculty of Medicine, Department of Laboratory Medicine &amp; Pathobiology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.214"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(12)80312-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000139066.77892.04"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009543"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.09.016"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-198806000-00010"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177451"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1991.200"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000095248.91994.D3"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000146121.72699.86"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000060"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1502"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004070578"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3485-4"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.25.5.1111"},{"key":"e_1_2_7_17_1","first-page":"285","article-title":"The \"point of no return\" and the rate of progression in the natural history of IgA nephritis","volume":"52","author":"Scholl U","year":"1999","journal-title":"Clin Nephrol"},{"key":"e_1_2_7_18_1","first-page":"690","article-title":"\"Point of no return (PNR)\" in progressive IgA nephropathy: significance of blood pressure and proteinuria management up to PNR","volume":"18","author":"Komatsu H","year":"2005","journal-title":"J Nephrol"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199311113292004"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1470320316668434"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008040416"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1303154"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1208799"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-0621"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.18269"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1275-6"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015111230"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.09.020"}],"container-title":["Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.13828","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nep.13828","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.13828","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T13:38:46Z","timestamp":1693661926000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nep.13828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1111\/nep.13828"],"URL":"https:\/\/doi.org\/10.1111\/nep.13828","archive":["Portico"],"relation":{},"ISSN":["1320-5358","1440-1797"],"issn-type":[{"value":"1320-5358","type":"print"},{"value":"1440-1797","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]},"assertion":[{"value":"2020-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}