Plasma ghrelin levels as a predictor of adverse renal events due to cisplatin-based chemotherapy in patients with esophageal cancer

Objective

Although combination chemotherapy with docetaxel, cisplatin and 5-fluorouracil demonstrates high response rates in esophageal squamous cell carcinoma, patients treated with docetaxel, cisplatin and 5-fluorouracil frequently experience acute kidney injury. Ghrelin has shown renal protective effects in an experimental acute kidney injury model by reducing tubular apoptosis. In this prospective observational study, we evaluated the association between plasma ghrelin concentrations and docetaxel, cisplatin and 5-fluorouracil-related acute kidney injury.

Methods

Forty consecutive patients with esophageal squamous cell carcinoma who received docetaxel, cisplatin and 5-fluorouracil from October 2013 to July 2014 were enrolled in this study. Serum creatinine and urinary α-1 microglobulin, a marker of renal tubular damage, were measured six times during chemotherapy.

Results

The increases of creatinine level which is defined in Common Terminology Criteria for Adverse Event were observed less frequently in patients with acyl ghrelin concentrations of ≥9.6 fmol/ml (HAG group) than in those with concentrations <9.6 fmol/ml on Day 2 (LAG group) (P= 0.024). Serum creatinine was significantly lower in the HAG group than in the LAG group (Day 8: 0.79 ± 0.16 vs. 0.97 ± 0.26, P = 0.024; Day 11: 0.85 ± 0.19 vs. 1.08 ± 0.34 mg/dl, P = 0.049). Urinary α-1 microglobulin levels were significantly lower in the HAG group than in the LAG group (Day 4: 2.48 ± 1.83 vs. 3.33 ± 1.41, P = 0.011; Day 8: 4.67 ± 5.50 vs. 5.09 ± 2.54, P = 0.011; Day 11: 11.55 ± 13.78 vs. 16.43 ± 17.84 mg/l, P = 0.020).

Conclusions

Plasma acyl ghrelin concentrations on Day 2 of chemotherapy may be a potential predictor of docetaxel, cisplatin and 5-fluorouracil-induced acute kidney injury.

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