Clinical Features， Molecular Mechanisms and Therapeutic Strategies of Aristolochic Acid-Induced Nephrotoxicity

It is reported that aristolochic acid（AA）not only has the definite nephrotoxicity but also causes the 3 different types of aristolochic acid nephropathy（AAN），which is different from the mutational signature of AA in inducing hepatocellular carcinomas. The clinical features of AA-induced nephrotoxicity include the lack of specific symptoms，a small amount of tubular proteinuria，the progressive renal failure，anemia and the extensive renal interstitial fibrosis with few infiltrated cells，along with tubular atrophy. The molecular mechanisms of AA-induced nephrotoxicity mainly refer to the induction of renal cellular apoptosis by affecting microRNAs（miRNAs），endoplasmic reticulum stress and oxidative stress directly or indirectly. In addition，renal inflammation is probably related to the molecular mechanism of AA-induced nephrotoxicity. The therapeutic strategies of AA-induced nephrotoxicity contain the low-dosage of glucocorticoids，prostaglandin E₁，bone marrow mesenchymal stem cells and Chinese herbal compound prescriptions and their extracts. Recently Chinese government has maintained strict controls on Chinese medicinal materials and Chinese traditional patent medicines containing AA，so that the incidences of AA-induced nephrotoxicity and AAN have been decreasing year by year. Nevertheless，Chinese herbal medicines（CHM） related drug-induced kidney injury（DKI）cannot be ignored，in which，establishing the evaluation methods of nephrotoxicity of CHM is the key point to understand the molecular mechanisms and explore the therapeutic strategies.