title: The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats.
abstract: BACKGROUND
  Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator.
  
  
  METHODS
  Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end.
  
  
  RESULTS
  Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months.
  
  
  CONCLUSIONS
  Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings.
authors.affiliation: Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ruud R G
authors.initials: RR
authors.lastname: Bueters
authors.forename: Annelies
authors.initials: A
authors.lastname: Jeronimus-Klaasen
authors.forename: Nuria
authors.initials: N
authors.lastname: Maicas
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Lambertus P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: Michiel F
authors.initials: MF
authors.lastname: Schreuder
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology; D005665:Furosemide / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D000209:Acute-Phase Proteins; D004232:Diuretics; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D006852:Hydrochlorothiazide; D012965:Sodium Chloride; D005665:Furosemide