Osteopontin and fatty acid binding protein in ifosfamide-treated rats

Abstract

Introduction: Ifosfamide (IF) is a cytostatic that exhibits adverse nephrotoxic properties. Clinically, IF-induced nephrotoxicity takes various forms, depending on applied dose and length of treatment. Objectives: The aim of the study was to evaluate the two proteins: osteopontin (OP) and fatty acid binding protein (FABP), as markers of kidney function in rats treated with ifosfamide. Material and Methods: Rats receiving a single IF dose (250 mg/kg b.w.; group 1) or treated with five consecutive IF doses administrated on following days (50mg/kg b.w.; group 3), compared with control groups 2 and 4, respectively, were studied. Kidney function was assessed using classical (urea, creatinine) and novel (FABP, OP) laboratory parameters and by histopathology. Results: Single IF dose administration resulted in significant total proteinuria with urinary concentrations and 24-hour excretions of both FABP and OP comparable to the appropriate control. In rats treated with five consecutive IF doses, the urinary concentrations and 24-hour excretion of both FABP and OP were significantly higher compared to the appropriate control. The development of cystitis was revealed in groups 1 and 3, which was not accompanied by significant histopathological kidney damage. Conclusions: Both OP and FABP may be useful laboratory markers of tubulopathy in the early stage of chronic nephrotoxicity of ifosfamide.