A nurse is caring for a client receiving cisplatin chemotherapy. Which nursing intervention is the most important priority to prevent nephrotoxicity?

Cisplatin is a highly effective platinum-based antineoplastic agent used for solid tumors such as ovarian cancer, but its clinical utility is significantly limited by dose-dependent nephrotoxicity. The client in this scenario has a baseline serum creatinine of 0.9 mg/dL and BUN of 18 mg/dL, which are within normal limits, but the risk of acute kidney injury (AKI) escalates with cumulative cycles. Cisplatin-induced nephrotoxicity (CIN) occurs in approximately 30% of patients and is primarily driven by the accumulation of cisplatin within renal proximal tubular cells, where it forms toxic thiol-cisplatin conjugates via the enzyme cysteine conjugate β-lyase 1 ^[1][4]. This process leads to tubular cell apoptosis, oxidative stress, and a decline in glomerular filtration rate.

The most important priority nursing intervention to prevent CIN is ensuring adequate hydration with normal saline before and after infusion (Option 4). Aggressive intravenous volume expansion with isotonic saline remains the cornerstone of nephroprotection because it increases renal plasma flow, dilutes the concentration of cisplatin in the renal tubules, and accelerates its urinary excretion, thereby reducing the contact time between the drug and tubular epithelial cells. Current evidence underscores that beyond hydration and magnesium supplementation, no pharmacologic agent has definitively proven effective for preventing CIN in clinical practice ^[4]. While mannitol has historically been used as a forced diuresis adjunct, a recent meta-analysis of randomized controlled trials found that the clinical evidence for its nephroprotective benefit remains inconclusive, and its use does not replace the fundamental need for robust saline hydration ^[3]. A large multicenter retrospective study comparing mannitol and furosemide for forced diuresis similarly highlighted that the choice of diuretic is secondary to the primary strategy of maintaining high urine output through volume loading ^[2].

• Option 1: Monitoring serum creatinine and BUN is essential for detecting nephrotoxicity early, but it is a surveillance measure, not a preventive one. By the time creatinine rises, significant tubular damage has already occurred. Prevention through hydration takes precedence over monitoring.


• Option 2: Administering antiemetics is a critical component of cisplatin care due to its high emetogenic potential, but this intervention targets gastrointestinal toxicity, not the pathophysiologic mechanism of renal tubular injury.


• Option 3: Assessing for peripheral neuropathy addresses cisplatin's dose-limiting neurotoxicity. While important for safety and quality of life, it does not mitigate the risk of AKI, which is the immediate threat to organ function during this third cycle of treatment.

The mechanism of CIN involves cisplatin entering renal proximal tubular cells via the organic cation transporter 2 (OCT2). Once intracellular, the drug undergoes enzymatic activation by cysteine conjugate β-lyase 1 to form a highly reactive thiol-cisplatin conjugate, which directly damages mitochondrial DNA and proteins, triggering cell death ^[1]. Adequate saline hydration works upstream of this pathway by reducing the luminal concentration of cisplatin in the proximal tubule, thus limiting its cellular uptake. This mechanistic understanding explains why hydration is the single most effective and evidence-based nursing intervention. Investigational agents such as flopropione, which inhibits the β-lyase enzyme, and SGLT2 inhibitors are being explored in preclinical and early-phase trials to directly block the intracellular toxicity cascade, but they are not yet standard of care ^[1][4].