{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T20:31:10Z","timestamp":1760646670779,"version":"3.37.3"},"reference-count":29,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:00:00Z","timestamp":1499731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Dutch Kidney Foundation","doi-asserted-by":"publisher","award":["KJPB.08.06"],"award-info":[{"award-number":["KJPB.08.06"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Up to two\u2010thirds of premature born neonates are treated for infections with aminoglycosides such as gentamicin. Although acute toxicities are well described, there is uncertainty on developmental changes after treatment of premature born neonates. We studied the effect of gentamicin and ceftazidime on kidney development in the rat. Additionally, we evaluated the modulating effect of extrauterine growth restriction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>On postnatal day (PND) 2, Wistar rats were cross\u2010fostered into normal sized litters (12 pups) or large litters (20 pups) to create normal food (NF) or food restricted (FR) litters to simulate growth restriction and dosed daily intraperitoneally with placebo, 4 mg\/kg of gentamicin or 50 mg\/kg ceftazidime until PND 8. Gentamicin pharmacokinetics were studied in a separate group of animals. Kidneys were weighed. Renal expression of 18 developmental genes was evaluated by quantitative PCR on PND 8. On PND 35, glomerular number was assessed by stereology and glomerular generations were counted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Food restricted litters showed 22% less body weight compared with controls by day 35 (<jats:italic>p<\/jats:italic> &lt; 0.001), 1.4\u2010 to 1.5\u2010fold down regulation of <jats:italic>Renin<\/jats:italic>, <jats:italic>Oat1<\/jats:italic>, and <jats:italic>Agtr1a<\/jats:italic> (<jats:italic>p<\/jats:italic> &lt; 0.05) expression and a 12% reduction in glomerular numbers (mean 30841 vs. 35187, <jats:italic>p<\/jats:italic> &lt; 0.001), whereas glomerular generation count was unaffected. Gentamicin pharmacokinetic parameters were found to be in a human clinical range (mean maximum concentration in plasma of 4.88 mg\/L and mean area under the plasma\u2010concentration time curve up to the last measured concentration after 4 hr of 10.71 mg.h\/L for sexes combined) and all endpoints were unaffected. Ceftazidime reduced <jats:italic>Renin<\/jats:italic> expression by 1.7\u2010fold (<jats:italic>p<\/jats:italic> &lt; 0.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our experiments showed that gentamicin at clinical levels did not disturb kidney development, ceftazidime can affect Renin expression, and extrauterine growth restriction impairs kidney development, but did not modulate potential drug toxicity. Birth Defects Research 109:1228\u20131235, 2017. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1071","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T10:11:16Z","timestamp":1499767876000},"page":"1228-1235","source":"Crossref","is-referenced-by-count":1,"title":["Early postnatal gentamicin and ceftazidime treatment in normal and food restricted neonatal wistar rats: Implications for kidney development"],"prefix":"10.1002","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4885-8597","authenticated-orcid":false,"given":"Ruud R.G.","family":"Bueters","sequence":"first","affiliation":[{"name":"Department of Pediatric Nephrology Radboud University Medical Center Nijmegen the Netherlands"},{"name":"Radboud Institute for Molecular Life Science Nijmegen the Netherlands"},{"name":"Preclinical Development &amp; Safety, Janssen Research &amp; Development, Division of Janssen Pharmaceutica NV Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annelies","family":"Jeronimus\u2010Klaasen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology Radboud University Medical Center Nijmegen the Netherlands"},{"name":"Radboud Institute for Molecular Life Science Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger J.M.","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Department of pharmacy Radboud University Medical Centre Nijmegen the Netherlands"},{"name":"Radboud Institute for Health Science Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lambertus P.","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology Radboud University Medical Center Nijmegen the Netherlands"},{"name":"Radboud Institute for Molecular Life Science Nijmegen the Netherlands"},{"name":"Department of Pediatrics University Hospital Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiel F.","family":"Schreuder","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology Radboud University Medical Center Nijmegen the Netherlands"},{"name":"Radboud Institute for Molecular Life Science Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,11]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000355734"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2014.127"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.21161"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000442674"},{"issue":"2","key":"e_1_2_5_6_1","first-page":"F466","article-title":"Effects of reactive oxygen species on cultured rat mesangial cells and isolated rat 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