Urine biomarkers after acute kidney injury in rats induced by gentamycin / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the time and dose relation of new urine bio markers in rat model of acute kidney injury induced by genta mycin (GM)to search for more sensitive,noninvasive and specific markers than traditional approaches to monitor nephrotoxicity.METHODS SD Rats were im treated with GM5,20,80 mg·kg -1 or saline once daily.Rats were randomly divided into 20 subgroupstreated for 1 ,3,7,14 d and 14 d followed with 28 d recovery period.Ten rats per group (5 rats per sex)were scarified at 24 h after the last dosing or the end of recovery period.Blood sa mples were col-lected for blood urea nitrogen (BUN)and creatinine(CRE)analysis.Urine was collected at each nec-ropsy for urine protein by dry che mistry method,for kidney injury molecule-1 (KIM-1 )analysis by ELISA, and for β2-microglobulin (β2-MG)analysis by ELISA.Kidneys were obtained for histological exa mination after HE stains.RESULTS Positive protein(3 +)was noted for several fe male animals treated for 7 or 14 d at 80 mg·kg -1 and the tendency of recovery were noted at the end of recovery period.Co mpared with those in saline control group treated for 7 d,the seru m BUN and CRE levels for fe males and the CRE level for males were significantly increased at 80 mg·kg -1 (P 0.05).When treated for 14 d,the seru m BUN and CRE levels for fe males and males at 80 mg·kg -1 and the seru m CRE level for fe males at 20 mg·kg -1 were significantly increased when compared with those in saline control group(P <0.05). The seru m BUN and CRE recovered to base line for all animals treated for 14 d followed by a 28 d recov-ery period.Histopathological observation of kidney tissues indicated that focal tubule dilatation was noted for animals treated for 3 d at 20 and 80 mg·kg -1 ,infla mmatory cell infiltration and focal tubule dilatation were noted at 20 mg·kg -1 and focal renal tubular epithelial cell degeneration,infla mmatory cell infiltra-tion,focal casts (lightly)were noted at 80 mg·kg -1 for animals treated for 7 or 14 d.For animals treated for 14 d followed by a 28 d recovery period,only basophilic tubules and renal casts were noted at 80 mg·kg -1 .New urine bio markers determination indicated that KIM-1 level was significantly increased at 20 and 80 mg·kg -1 for animals treated for 3,7 or 14 d when compared with that in saline control group (P<0.05).For animals treated for 14 d followed by a 28 d recovery period,the KIM-1 level was still significantly higher than saline control group for males and fe males at 80 mg·kg -1 and males at 20 mg·kg -1 (P <0.05 ),but there was evidence for reversal.The β2-MG level was significantly increased at 80 mg·kg -1 for animals treated for 3 d(P<0.05),at 20 or 80 mg·kg -1 for animals treated for 7 or 14 d(P<0.05 or P<0.01 ),when compared with that in the saline control group.For animals treated for 14 d followed by a 28 d recovery period,the β2-MG level was still significantly higher than saline control group for males and fe males at 80 mg·kg -1 and fe males at 20 mg·kg -1 (P <0.05),but there was also evidence for reversal.CONCLUSION Urine KIM-1 and β2-GM are more sensitive and specific markers for early diagnosis of kidney injury induced by GM when compared with the traditional approaches to monitor nephrotoxicity.