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.
- 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.

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 m2; on day 6, 51.0 ± 2.5 mL/min/1.73 m2) 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.