During high-dose methotrexate therapy, which organ pairs are monitored for toxicity?

• A. Heart and kidneys
• B. Lungs and kidneys
• C. Heart and liver
• D. Liver and kidneys

Answer: (D)

In high-dose methotrexate therapy, the organs most at risk are those involved in clearing the drug and those prone to toxicity from it. The liver processes methotrexate and can develop hepatotoxicity, so liver function tests are routinely monitored. The kidneys are the primary route of MTX elimination, and high doses can cause nephrotoxicity if the drug or its metabolites precipitate in the renal tubules or if hydration and urine pH aren’t adequately managed. That’s why renal function tests and urine output are closely watched. Monitoring both liver and kidney function allows early detection of hepatotoxicity and nephrotoxicity and supports timely supportive measures like hydration, urine alkalinization, and leucovorin rescue. Other organ systems can be affected in different contexts, but liver and kidneys are the main focus for toxicity monitoring with this regimen.