So you’ve prescribed methotrexate for your patient with rheumatoid arthritis.
Good. Sensible. It’s been the cornerstone of RA management for decades.
Cheap, effective, dependable.
Problem is, it’s got all these pesky side effects:
Mucositis, myelosuppression, pneumonitis and fibrosis popping up everywhere.
It’s not exactly the friendliest of drugs.
Which is why we monitor. Relentlessly.

FBCs. LFTs. U&Es. The whole biochemical surveillance package. Unfortunately, these blood tests behave like toddlers. Leave them unsupervised, and you can be absolutely certain something expensive is being damaged somewhere.

In a study published in Arthritis Research & Therapy, researchers conducted a retrospective analysis to assess methotrexate's impact on kidney and liver-related adverse reactions in RA patients.

They looked at 10,319 adverse drug reaction reports where methotrexate was the suspected culprit. Outcomes were categorised as either:

Fatal: meaning the patient died or

Non-fatal: which included life-threatening events, prolonged hospitalisation, disabilities and so on.

What did they find?

But when it came to deaths, the kidneys were ahead. Among kidney-related side effects, fatalities occurred in 21.1% of cases compared to only 5.8% with liver toxicity. Suddenly, the liver looks like the least of your worries.

More Takeaways

Longer methotrexate use meant more kidney problems. Patients with kidney reactions had been on methotrexate for a median of 16.2 months, compared to 9.9 months for liver issues.

Older and overmedicated was a bad combo. Liver-related deaths were more common in older patients who were also stacking up comedications like corticosteroids, acetaminophen and metamizole.

Highest mortality in mixed disease. Patients with both liver and kidney involvement had the highest death rates, especially if they were mixing in NSAIDs, acetaminophen or metamizole.

In their own words, the authors put it plainly:

"Because drug management in patients with RA using methotrexate is a complex matter, precise and standardised recommendations on when and how frequently renal function needs to be tested to detect early signs of renal impairment might be helpful to prevent fatal outcomes."

The Bottom Line

Whilst LFTs are important for monitoring, maybe don’t let the kidneys feel left out.