Early prediction of cisplatin-induced nephrotoxicity by urinary vanin-1 in patients with urothelial carcinoma.
Cisplatin is a widely used anticancer drug, but its nephrotoxicity is a serious problem. To examine whether the novel biomarker, urinary vanin-1, could predict reduction in renal function after dosing of cisplatin. We conducted a prospective single-center pilot study of 24 patients with urothelial carcinoma who received cisplatin-based chemotherapy between 2012 and 2015. The primary outcome was a 20% or greater decline in estimated glomerular filtration rate (eGFR) from baseline within the first 6days of cisplatin. Urine concentration of creatinine, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and NAG (N-acetyl-β-d-glucosaminidase) as well as vanin-1 were measured during the perioperative period. During 6days after cisplatin, 37.5% (9/24) of patients showed more than 20% decline in eGFR (baseline, 68.8±11.1mL/min/1.73m(2); on day 6, 51.0±2.5mL/min/1.73m(2)) and this reduction persisted until day 10. Urinary vanin-1, but not KIM-1, NGAL and NAG, significantly elevated early on day 3 after cisplatin, which preceded the elevation of serum creatinine on day 6. Sensitivity and specificity of a cutoff point of urinary vanin-1 (9.31ng/mg Cr) on day 3 were calculated to be 66.7% (95% CI: 0.30-0.93) and 83.3% (95% CI: 0.52-0.97), respectively, for predicting 20% decline in eGFR during 6days after cisplatin. These data suggest that urinary vanin-1 is an early predictive biomarker for decline in eGFR in patients with urothelial carcinoma after dosing of cisplatin.
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan. Electronic address: hosohata@gly.oups.ac.jp.
Keiko
K
Hosohata
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan; Department of Urology, Jichi Medical University, Tochigi 329-0498, Japan.
Satoshi
S
Washino
Department of Urology, Jichi Medical University, Tochigi 329-0498, Japan.
Taro
T
Kubo
Department of Urology, Jichi Medical University, Tochigi 329-0498, Japan.
Shinsuke
S
Natsui
Department of Urology, Jichi Medical University, Tochigi 329-0498, Japan.
Akira
A
Fujisaki
Department of Urology, Jichi Medical University, Tochigi 329-0498, Japan.
Shinsuke
S
Kurokawa
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan.
Hitoshi
H
Ando
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan.
Akio
A
Fujimura
Department of Urology, Jichi Medical University, Tochigi 329-0498, Japan.
Tatsuo
T
Morita
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000503:physiopathology / Q000652:urine; D000368:Aged; D000369:Aged, 80 and over; D000581:Amidohydrolases / Q000652:urine*; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D015415:Biomarkers / Q000652:urine; D002277:Carcinoma / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine*; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D058851:GPI-Linked Proteins / Q000652:urine; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D014571:Urologic Neoplasms / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine*
D000970:Antineoplastic Agents; D015415:Biomarkers; D058851:GPI-Linked Proteins; D000581:Amidohydrolases; C022314:pantetheinase; D002945:Cisplatin
Cisplatin; Early biomaker; Renal function; Urothelial carcinoma