Does Cisplatin (Cis-diammineplatinum) induce Acute Kidney Injury (AKI)?

From the Guidelines

Cisplatin is a well-known nephrotoxic agent that can induce acute kidney injury (AKI) in patients, particularly at higher doses, as evidenced by the study published in Kidney International in 2020 1.

Mechanism of AKI

The mechanism of cisplatin-induced AKI involves direct tubular toxicity, particularly to the proximal tubules, through oxidative stress, inflammation, and apoptosis of renal cells. Cisplatin accumulates in the kidneys at higher concentrations than in other tissues, explaining its selective renal toxicity.

Prevention Strategies

Prevention strategies include aggressive hydration with normal saline (1-2 L before and after cisplatin administration), maintaining adequate urine output, and sometimes administering amifostine as a cytoprotective agent.

Dose Adjustments and Monitoring

Dose adjustments are necessary for patients with pre-existing kidney disease, and renal function should be monitored before each cycle of cisplatin therapy, as recommended in the guidelines for ovarian cancer treatment published in the Journal of the National Comprehensive Cancer Network in 2021 1.

Key Considerations

Some key considerations for minimizing the risk of cisplatin-induced AKI include:

• Ensuring normal renal function before starting treatment
• Monitoring patients carefully for myelosuppression, dehydration, electrolyte loss, end-organ toxicities, and other toxicities after each cycle of chemotherapy
• Providing expert nursing care to decrease complications
• Administering intravenous fluids before and after IP chemotherapy to prevent certain toxicities, such as nausea, vomiting, electrolyte imbalances, and metabolic toxicities.

Conclusion is not allowed, so the answer will be ended here.

From the FDA Drug Label

ADVERSE REACTIONS Nephrotoxicity Dose-related and cumulative renal insufficiency, including acute renal failure, is the major dose-limiting toxicity of cisplatin. Renal toxicity has been noted in 28% to 36% of patients treated with a single dose of 50 mg/m 2 It is first noted during the second week after a dose and is manifested by elevations in BUN and creatinine, serum uric acid and/or a decrease in creatinine clearance. Renal toxicity becomes more prolonged and severe with repeated courses of the drug. Renal function must return to normal before another dose of cisplatin can be given.

Cisplatin induces Acute Kidney Injury (AKI): Yes, cisplatin can cause nephrotoxicity, including acute renal failure, which is a major dose-limiting toxicity of the drug. Renal toxicity has been observed in 28% to 36% of patients treated with a single dose of 50 mg/m^2, and it can become more prolonged and severe with repeated courses of the drug 2.

From the Research

Cisplatin and Acute Kidney Injury (AKI)

• Cisplatin is a chemotherapy drug that can cause AKI, a well-known complication of cisplatin-based chemotherapy 3, 4, 5, 6, 7
• The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney 4, 5
• Cisplatin nephrotoxicity is cumulative and dose-dependent, and often necessitates dose reduction or withdrawal 4

Incidence and Risk Factors of Cisplatin-Associated AKI

• The incidence of cisplatin-associated AKI is approximately 30-68% of patients treated with cisplatin 3, 6
• Risk factors for cisplatin-associated AKI include African American race, high dose of cisplatin, and repetitive administration of cisplatin 3, 6
• Patients who develop AKI are at risk for long-term decline in kidney function and the development of chronic kidney disease (CKD) 3, 5, 6

Mechanisms and Consequences of Cisplatin-Induced AKI

• Cisplatin causes AKI by inducing proximal tubular injury, DNA damage, apoptosis, inflammation, oxidative stress, and vascular injury 4, 5
• The consequences of cisplatin-induced AKI include long-term renal function decline, increased risk of CKD, and decreased patient survival 3, 5, 6
• Repetitive administration of cisplatin can cause subclinical kidney injury, leading to CKD over time 5, 6

Prevention and Treatment of Cisplatin-Induced AKI

• Hydration and avoiding additional nephrotoxic drugs are commonly used protocols to prevent cisplatin-induced AKI, but there are no clear guidelines regarding this approach 5
• Future perspectives for preventing nephrotoxicity may include the use of natural products, such as flavonoids or saponins, or pharmacological products, such as aprepitant 5
• Researchers are exploring potential therapeutic targets for cisplatin-induced kidney injury, including cell death, cell senescence, endoplasmic reticulum stress, autophagy, and immune cell activation 6