Objective: To observe the renal changes of aristolochic acid-induced nephrotoxicity by long-term using different dose of Caulis Aristolochiae Manshuriensis Extract (CAME) in rats

and investigate the relationship between the changes and blood aristolochic acid-A concentration. Method: Male SD rats were randomized into 5 groups: normal diet control group

low-salt diet control group

Low-

Mid-

and High-dose groups. Renal function and morphological changes in renal tissue were observed at 4 and 6 weeks after treatment with CAME

respectively. The aristolochic acid-A concentration in blood was determined by LC-MS-MS method. Result: Compared with low-salt diet control group

the urine volumes in 3 groups were increased at the 2nd weeks. At the 4th weeks

the urine volumes were decreased; other renal changes in low- and mid-dose groups were not obvious; the levels of urine protein and BUN were remarkably increased in high-dose group. At the 6th weeks

the urine volume was decreased in high-dose group and the levels of urine protein

Crea and BUN were significantly increased. Morphologic changes consisted of vacuolization of renal tubular cells

hyalinization of small arterioles and the light renal interstitial fibrosis. All the injury changes in High-dose group were more severe than those in low- and mid-dose groups. The parameters in two control groups had no statistical significance. The plasma aristolochic acid-A concentration was very low. Conclusion: Long-term use of CAME in rats results in renal function and morphological changes

which correlated with time and dosage of used CAME and might be independence to plasma aristolochic acid-A concentration.