Early prediction of cisplatin-induced nephrotoxicity by urinary vanin-1 in patients with urothelial carcinoma. (1st June 2016)

• Record Type: Journal Article
• Authors: Hosohata, Keiko; Washino, Satoshi; Kubo, Taro; Natsui, Shinsuke; Fujisaki, Akira; Kurokawa, Shinsuke; Ando, Hitoshi; Fujimura, Akio; Morita, Tatsuo
• Is Part Of: Toxicology. Volume 359/360(2016)
• Page Start: 71
• Page End: 75
• Publication Date: 2016-06-01
• Subjects: eGFR estimated glomerular filtration rate -- KIM-1 kidney injury molecule-1 -- NAG N-acetyl-β-d-glucosaminidase -- NGAL neutrophil gelatinase-associated lipocalin -- GC gemcitabine and cisplatin -- MVAC methotrexate, vinblastine, doxorubicin, adiamycin, and cisplatin -- UC urothelial carcinoma; Early biomaker -- Renal function -- Cisplatin -- Urothelial carcinoma; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2016.06.011
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: Cisplatin is a widely used anticancer drug, but its nephrotoxicity is a serious problem. Traditional markers of kidney function, such as serum creatinine, are suboptimal, because they are not sensitive measures of kidney injuries. Sensitivity and specificity of urinary vanin-1 for reduction in eGFR after cisplatin were high. Urinary vanin-1 could predict the reduction in eGFR at a relatively early stage after cisplatin. Abstract: 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 6 days 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 6 days after cisplatin, 37.5% (9/24) of patients showed more than 20% decline in eGFR (baseline, 68.8 ± 11.1 mL/min/1.73 m 2 ; on day 6, 51.0 ± 2.5 mL/min/1.73 m 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 (9.31 ng/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 6 days 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.