title: Impact of acute kidney injury defined by CTCAE v4.0 during first course of cisplatin-based chemotherapy on treatment outcomes in advanced urothelial cancer patients.
abstract: BACKGROUND
  The Kidney Disease: Improving Global Outcomes group (KDIGO) defined acute kidney injury (AKI) as an elevation of serum creatinine (sCR) exceeding 0.3 mg/dl within 48 h. The widely used adverse events criteria for chemotherapy, Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAE v4.0), also defined AKI as sCR exceeding 0.3 mg/dl, but with no provision of a time course. Here, we attempted to clarify the impact of AKI (CTCAE v4.0) during cisplatin-based chemotherapy on clinical outcome of patients with advanced urothelial cancer (UC).
  
  
  METHODS
  This multicenter retrospective study included 230 UC patients who received cisplatin-based chemotherapy.
  
  
  RESULTS
  During the first chemotherapy course, AKI (CTCAE v4.0) episodes were observed in 61 patients (26.5 %), whereas only four patients (1.5 %) experienced AKI (KDIGO) episodes. Both the pretreatment estimated glomerular filtration rate (eGFR) and creatinine clearance by Cockcroft-Gault formula were not efficient predictors for the development of AKI (CTCAE v4.0). AKI (CTCAE v4.0) impacted renal function: at the start of second-course chemotherapy, the average eGFR of the patients with AKI (CTCAE v4.0) was 54.1 ml/min/1.73 m2, significantly lower than that of patients without AKI (CTCAE v4.0) (63.4 ml/min/1.73 m2). As a result, only 57.4 % of patients with AKI (CTCAE v4.0) received the planned treatment at the second course. The survival of the patients who developed AKI (CTCAE v4.0) was significantly worse than that of the patients who did not. The 3-year OSs were 10.3 and 21.4 %, respectively (P = 0.02).
  
  
  CONCLUSIONS
  The present study demonstrated that AKI (CTCAE v4.0) during chemotherapy had a negative impact on both the intensity of subsequent chemotherapy and oncological outcomes.
authors: Department of Urology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
authors: Ryutaro
authors: R
authors: Ishitsuka
authors: Department of Urology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
authors: Jun
authors: J
authors: Miyazaki
authors: Department of Urology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
authors: Daishi
authors: D
authors: Ichioka
authors: Department of Urology, Akita University Graduate School of Medicine, Akita, 010-8502, Japan.
authors: Takamitsu
authors: T
authors: Inoue
authors: Department of Urology, Shiga University of Medical Science, Shiga, 522-8522, Japan.
authors: Susumu
authors: S
authors: Kageyama
authors: Department of Urology, Faculty of Medicine, Kagawa University, Kagawa, 761-0701, Japan.
authors: Mikio
authors: M
authors: Sugimoto
authors: Department of Urology, Tohoku University, Graduate School of Medicine, Miyagi, 980-8575, Japan.
authors: Koji
authors: K
authors: Mitsuzuka
authors: Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
authors: Yoshiyuki
authors: Y
authors: Matsui
authors: Department of Urology, Hyogo College of Medicine, Hyogo, 663-8501, Japan.
authors: Yusuke
authors: Y
authors: Shiraishi
authors: Department of Urology and Andrology, Kansai Medical University, Osaka, 573-1191, Japan.
authors: Hidefumi
authors: H
authors: Kinoshita
authors: Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692, Japan.
authors: Hironobu
authors: H
authors: Wakeda
authors: Department of Urology, Tokai University School of Medicine, Kanagawa, 259-1193, Japan.
authors: Takeshi
authors: T
authors: Nomoto
authors: Department of Urology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
authors: Eiji
authors: E
authors: Kikuchi
authors: Department of Urology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
authors: Koji
authors: K
authors: Kawai
authors: Department of Urology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. nishiuro@md.tsukuba.ac.jp.
authors: Hiroyuki
authors: H
authors: Nishiyama
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology
chemical_list: D015415:Biomarkers; D003404:Creatinine; D002945:Cisplatin
keywords: Acute kidney injury; Chemotherapy; Cisplatin; Serum creatinine; Urothelial cancer