Glutamine synthetase as sensitive biomarker to detect nephrotoxicity induced by colistin in rat

K Zeghal1, Z Ghlissi1, T Rebai2, F Ayedi3, Z Sahnoun1, A Hakim1. 1Faculty of Medicine, University of Sfax, Laboratory of Pharmacology, 3029 Sfax, Tunisia, 2Faculty of Medicine, University of Sfax, Laboratory of Histology and Embryology,3029 Sfax, Tunisia, 3Habib Bourguiba University Hospital of Sfax, Department of Biochemistry,3029 Sfax, Tunisia

Aim: Nephrotoxicity is a frequent problem of colistin treatment. Early recognition could help clinical management and make avoid acute kidney injury. Glutamine synthetase, an enzyme localised in the S3 segment of proximal tubule, has been suggested to contribute to prediction of an early nephrotoxicity.

Methods: Eighteen male Wistar rats were divided into three groups: control group (group 1) was injected intramuscularly with sodium chloride 0.9% (1 ml/kg), groups 2 and 3 (n=6 each) were treated intramuscularly with colistin at dose of 150 000 or 300 000 IU/kg/day body weight every 12 hours for 7 days, respectively. Everyday, urine samples from each rat of treated groups were collected to measure glutamine synthetase activity. Twelve hours after the last injection, all rats were sacrificed, kidneys were quickly removed and blood samples were collected. Microscopic examination of kidneys and measurements plasma creatinine and blood urea nitrogen was performed.

Results: Treated groups showed no alterations of blood urea nitrogen and plasma creatinine levels or histological change. However, a considerable increase in glutamine synthetase activity was observed.

Conclusion: Urine glutamine synthetase activity could be a sensitive marker of colistin involvement of the kidney than plasma creatinine or blood urea nitrogen, permitting to detect early S3 segment-specific injury of the proximal tubule at a functional stage before the definitive renal damage.