What are the considerations for passing a kidney stone while taking methotrexate (methotrexate)?

Management of Kidney Stones in Patients Taking Methotrexate

Patients taking methotrexate who develop kidney stones require careful monitoring of renal function, as methotrexate is primarily eliminated through the kidneys and any obstruction can lead to dangerous drug accumulation and toxicity.

Key Considerations for Kidney Stone Management in Methotrexate Users

Renal Function Assessment

• Methotrexate is eliminated almost entirely by the kidneys (85%) 1
• Impaired renal function significantly increases risk of methotrexate toxicity due to drug accumulation 1, 2
• Even low-dose methotrexate can impair kidney function, with studies showing significant decreases in glomerular filtration rate and tubular function 3

Immediate Actions When a Kidney Stone Is Suspected

1. Temporarily hold methotrexate until renal function is assessed and stone passage is complete
2. Monitor renal function with serum creatinine and BUN measurements
3. Assess for signs of methotrexate toxicity:
   • Fever/flu-like illness
   • Mouth ulceration
   • Unexplained bruising or bleeding
   • Nausea, vomiting, abdominal pain
   • Breathlessness or cough 4

Management Based on Stone Size and Location

For stones <10mm:

• Medical expulsive therapy (MET) can be considered if:
  • Pain is well-controlled
  • No clinical evidence of sepsis
  • Adequate renal functional reserve 4
• Periodic imaging to monitor stone position and assess for hydronephrosis 4
• Increased hydration to promote stone passage and prevent methotrexate accumulation

For stones >10mm:

• Surgical intervention likely required 4
• Options include:
  1. Shock wave lithotripsy (SWL)
  2. Ureteroscopy (URS)
  • URS yields significantly greater stone-free rates but has higher complication rates 4

Specific Precautions for Methotrexate Users

1. Hydration management:

   • Aggressive hydration (3-4 L/day) is crucial to prevent methotrexate accumulation 5
   • Urinary alkalinization to maintain pH >7.0 may be beneficial to prevent methotrexate crystal formation 5

2. Medication interactions:

   • Avoid NSAIDs for pain control as they can:
     • Decrease binding of methotrexate to albumin
     • Decrease renal tubular excretion
     • Lead to increased serum methotrexate levels 4, 5
   • Use alternative pain management (acetaminophen, opioids if necessary)

3. Laboratory monitoring:

   • More frequent monitoring of:
     • Complete blood count
     • Liver function tests
     • Renal function tests 4
   • Consider methotrexate level monitoring if available 1

4. Post-stone passage follow-up:

   • Assess renal function before restarting methotrexate
   • Consider dose reduction if evidence of residual renal impairment
   • Resume at lower dose with more frequent monitoring initially

Special Considerations

• Patients with pre-existing renal impairment are at particularly high risk and may require hospitalization for close monitoring during stone passage 2
• Elderly patients have declining renal function and are at higher risk for methotrexate toxicity 1
• Leucovorin rescue may be considered in cases where methotrexate levels are elevated due to acute kidney injury from stone obstruction 5

Prevention of Future Stones

• Maintain high fluid intake (2-3 L/day)
• Consider metabolic evaluation after stone passage to identify underlying causes
• Address modifiable risk factors for stone formation
• Regular monitoring of renal function while on methotrexate therapy 6

Remember that even temporary renal impairment from a passing kidney stone can lead to dangerous methotrexate accumulation, potentially causing severe toxicity including myelosuppression, mucositis, and worsening renal damage 7.