Methotrexate treats autoimmune diseases like rheumatoid arthritis, psoriasis, and Crohn’s disease. It also treats cancers like acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. It slows the growth of rapidly dividing cells, reducing inflammation in autoimmune conditions and inhibiting cancer cell proliferation.
How Methotrexate Affects Kidneys
Methotrexate is primarily eliminated from the body through the kidneys. If kidney function is impaired, methotrexate can accumulate in the bloodstream, leading to prolonged exposure and increased toxicity.
Higher doses of methotrexate, often used in cancer treatment, can directly impact kidney function, potentially causing acute kidney injury (AKI). Damage occurs through several mechanisms, including precipitation of methotrexate and its metabolites within renal tubules, obstructing them. Crystal formation is more likely in acidic urine. Direct toxicity to tubular cells, oxidative stress, inflammation, and reduced blood flow contribute.
Monitoring Kidney Health During Treatment
Monitoring kidney function is important during methotrexate therapy to detect early issues. Regular blood tests assess kidney health, including serum creatinine, a waste product filtered by kidneys. Increased creatinine levels indicate decreased kidney function.
Blood urea nitrogen (BUN) is another common test; elevated BUN levels also suggest suboptimal kidney function. Healthcare providers calculate the estimated glomerular filtration rate (eGFR) from these results. The eGFR estimates how well kidneys filter waste from blood.
These tests are performed at baseline before starting methotrexate and regularly throughout treatment. Monitoring may occur every 1-2 weeks initially, then every 1-2 months for long-term therapy, or more frequently for high-risk patients. Patients should report any new symptoms to their healthcare team, as these could signal kidney concerns.
Adjusting Treatment for Kidney Concerns
If a patient has pre-existing kidney impairment or develops kidney issues during methotrexate treatment, healthcare providers manage toxicity risk. Dosage adjustments are often necessary, as methotrexate elimination is reduced with impaired kidney function. Mild to moderate impairment may require dose reductions, while severe impairment might lead to temporary withholding or contraindication in advanced kidney disease.
Increased monitoring of kidney function and methotrexate levels is also implemented. Aggressive hydration and alkalinization of urine (maintaining a pH of 7 or higher) with sodium bicarbonate are often used to enhance methotrexate solubility and excretion, helping to prevent crystal formation in the tubules.
Certain co-medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and some antibiotics, can interfere with methotrexate excretion and increase its levels, so their use may need to be avoided or carefully managed. For high-dose methotrexate, rescue therapies like leucovorin are administered to counteract the drug’s effects on healthy cells and reduce toxicity. In severe cases of delayed methotrexate clearance due to impaired kidney function, glucarpidase may be used to rapidly break down circulating methotrexate.