Urinary parameters predictive and electrolyte disturbances of cisplatin-induced acute renal associated with cancer as a critical target of the chemotherapeutic agent in patients with solid tumors.

Abstract

Cisplatin (CP) is a remarkably effective Pt-based anticancer drug, but it also exhibits severe toxic side effects, including nephrotoxicity and ototoxicity, and CP nephrotoxicity is a major constraint for the treatment of solid tumors. This study was designed to evaluate the electrolyte and biochemical changes in dogs with acute kidney injury (acute renal failure) following administration of CP as a chemotherapeutic agent to exhibit broad efficacy in solid tumors. A total of 10 adult male dogs were selected (treated dogs = 7 and control dogs = 3). Cisplatin-treated animals were received 0.75 mg/kg via intravenous for 5 consecutive days. Urine and blood samples on days 0 (pre-dosing), 1, 2, 3, 4, 7, 10, 14, and 28 (post-dosing) were collected. For tracking the signs of toxicity with cisplatin, clinical examination was performed for 2 times a day. Serum samples were assayed urea, creatinine, sodium, chloride, potassium, calcium, phosphorus, and urine samples were used to measure creatinine. Serum creatinine levels indicating renal function (glomerular filtration rate) was 0.66 and 0.94 mg/dL in day 0, respectively, in treatment and control animals. After day 2, a significant change in creatinine was observed in treatment animals. On the end day of the study control and treatments, creatinine was measured with mean of 1.35 and 1.00 mg/dL, respectively. Electrolyte disturbances were observed after several days of cisplatin administration including changes in levels of sodium, potassium, phosphorus, calcium, and chloride. Clinical observations also identified CP toxicity. This study for the first time showed that compensation electrolyte abnormalities in dogs following administration of cisplatin is essential to prevent deaths by daily monitoring and measurement of electrolytes in patients. This may be advantageous if repetitive cycles of chemotherapy or subsequent administration of high dose chemotherapy were planned.