Cisplatin is a commonly used chemotherapeutic drug for cancer treatment, but its nephrotoxicity may lead to the deterioration of renal function. Previous work was focused on cisplatin-induced acute kidney disease, whereas the mechanism of chronic kidney disease (CKD) following cisplatin chemotherapy is largely unknown. Here we have characterized the mouse model of chronic kidney defects induced by repeated low dose cisplatin treatment. We have also established a relevant cell culture model. In the animal model, C57 mice were given weekly injection of 8 mg/kg cisplatin for 4 weeks. This led to a sustained decline of kidney function. These mice showed loss of kidney mass, interstitial fibrosis, continued activation of inflammatory cytokines, and appearance of atubular glomeruli. In the cell model, BUMPT mouse proximal tubular cell line was treated 4 times with 1-2 mM cisplatin, resulting in low levels of apoptosis and the expression of fibrosis proteins and profibrotic factors. These data suggest that repeated treatment with low dose cisplatin causes long-term renal pathologies with characteristics of chronic kidney disease.
American journal of physiology. Renal physiology. 2019 Sep 18 [Epub ahead of print]
Ying Fu, Juan Cai, Fanghua Li, Zhiwen Liu, Shaoqun Shu, Ying Wang, Yuxue Liu, Chengyuan Tang, Zheng Dong
Department of Nephrology, Second Xiangya Hospital at Central South University., Department of Nephrology, The Key Laboratory of Kidney Disease and Blood Purification of Hunan Province, Second Xiangya Hospital at Central South University,Changsha, Hunan, China., Nephrology, The Second Xiangya Hospital at Central South University., Nephrology, The Second Xiangya Hospital of Central South University, China., Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA, USA, United States.