Tubulointerstitial Injury Associated With Chemotherapeutic Agents Anushree C. Shirali, Mark A. Perazella  Advances in Chronic Kidney Disease  Volume 21, Issue 1, Pages 56-63 (January 2014) DOI: 10.1053/j.ackd.2013.06.010 Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions

Figure 1 Cisplatin-associated nephrotoxicity. Cisplatin causes kidney injury via multiple mechanisms. Uptake into proximal tubular cells is associated with toxicity via cell signaling pathways, inflammation, and increased oxidative stress. Vascular injury also causes tubular ischemia and acute kidney injury. OCT-2, organic cation transporter-2; RTEC, renal tubular epithelial cell; TNF-α, tumor necrosis factor-α. Advances in Chronic Kidney Disease 2014 21, 56-63DOI: (10.1053/j.ackd.2013.06.010) Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions

Figure 2 Ifosfamide-associated nephrotoxicity. Unlike cyclophosphamide, methotrexate is transported into proximal tubular cells via the OCT-2 on the basolateral membrane and is metabolized to the tubular toxic substance chloracetaldehyde. AKI, acute kidney injury; ATN, acute tubular necrosis; OCT, organic cation transporter-2. Advances in Chronic Kidney Disease 2014 21, 56-63DOI: (10.1053/j.ackd.2013.06.010) Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions

Figure 3 Prevention and treatment of methotrexate nephrotoxicity. High-risk patients more commonly develop nephrotoxicity from high-dose methotrexate. Preventive strategies include intravenous fluids, urinary alkalinization, and leucovorin rescue. When acute kidney injury develops and drug levels are excessive, glucarbidase and high-flux hemodialysis should be considered. HD, hemodialysis; IV, intravenous; GFR, glomerular filtration rate. Advances in Chronic Kidney Disease 2014 21, 56-63DOI: (10.1053/j.ackd.2013.06.010) Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions