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6952082 
Journal Article 
Adefovir accumulation and nephrotoxicity in renal interstitium: Role of organic anion transporters of kidney 
Zhou, Y; Yang, Y; Wang, P; Wei, M; Ma, Y; Wu, X 
2019 
1 
Life Sciences
ISSN: 0024-3205
EISSN: 1879-0631 
224 
41-50 
English 
30902543 
Common characteristics of drug induced nephrotoxicity are renal tubular and interstitial injury. Many studies have only focused on renal tubular injury. However, less is known about the effects of drugs in the renal interstitium on the nephrotoxicity. The aim of this study was to investigate the pharmacokinetics of adefovir (ADV) and the nephrotoxicity in the renal interstitium. Rats were treated with ADV alone or in combination with probenecid for 1, 7, 14, or 28 days. The renal interstitial fluid was collected by renal microdialysis. The concentration of ADV was determined by HPLC-MS/MS. Nephrotoxicity was evaluated by biochemical parameters or histological analysis. The results showed that organic anion transporters (OATs) inhibitor probenecid significantly increased the area under concentration-time curves (AUC) and peak concentration (Cmax) of ADV in the renal interstitium, while the clearance (CL) in the renal interstitium was decreased in the ADV plus probenecid group compared to the ADV groups. After long-term treatment, interstitial fibrosis was present in the ADV plus probenecid group, whereas no trace of that could be detected in the ADV groups. Furthermore, a decrease was observed in the expression of OATs/Oats, which was dependent upon the concentrations and time of ADV treatment. In conclusion, it is possible that ADV could be accumulated in the interstitium when Oats were inhibited, which could cause renal interstitial fibrosis. Simply reducing cell uptake in long-term treatment might not be an effective method to protect against chronic nephrotoxicity.