Assessing low-dose gentamicin-induced kidney injury in rats by analysis of urine.
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.
Nykjaer
Anders
A
Department of Medical Biochemistry, Aarhus University, DK 8000 Aarhus C, Denmark.
Schambye
Hans
H
Pedersen
Anders H
AH
Nielsen
Henning
H
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
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010743:Phospholipids