title: Assessing low-dose gentamicin-induced kidney injury in rats by analysis of urine.
abstract: BACKGROUND
  Gentamicin is an important aminoglycoside antibiotic used in clinics to combat infections from especially gram negative bacteria. A frequent side-effect of aminoglycoside antibiotics is a kidney injury consisting of necrosis of proximal tubular cells. It is important both in clinics and in research directed to eliminate or ameliorate this side-effect that a method is available for detection of injury at an early stage.
  
  
  METHODS
  We have therefore compared the sensitivity of four methods currently used in animal models to assess kidney injury induced by aminoglycoside antibiotics by applying them to the analysis of urine from male rats treated with low doses of gentamicin.
  
  
  RESULTS
  Excretion of phospholipids was significantly increased in contrast to excretion of N-acetyl-beta-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and protein. Assessment of phospholipiduria thus is the more sensitive noninvasive way to monitor initial renal injury induced by aminoglycoside antibiotics. A protocol is given for the serial analysis of urinary phospholipids allowing a considerable number of determinations to be carried out in the course of 2-3 days.
  
  
  CONCLUSIONS
  It is well known that all four considered methods do detect kidney damage induced in rats by high gentamicin doses far above doses used in clinics. The present investigation shows that only the analysis of the urinary phospholipids will detect damage induced by low doses of gentamicin. The method is relevant for animal model studies but will require considerable and innovative development for use in clinics.
authors.affiliation: Department of Medical Biochemistry, Aarhus University, DK 8000 Aarhus C, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Nykjaer
authors.forename: Hans
authors.initials: H
authors.lastname: Schambye
authors.forename: Anders H
authors.initials: AH
authors.lastname: Pedersen
authors.forename: Henning
authors.initials: H
authors.lastname: Nielsen
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000008:administration & dosage* / Q000633:toxicity; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000652:urine*; D008297:Male; D010743:Phospholipids / Q000378:metabolism / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D016482:Urinalysis / Q000379:methods
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010743:Phospholipids