Can Imatinib (Gleevec) affect kidney function, specifically causing Impaired renal function?

Imatinib's Effects on Kidney Function

Yes, imatinib can affect kidney function, causing both acute kidney injury and chronic decline in glomerular filtration rate in some patients. 1

Incidence and Severity of Renal Effects

Imatinib's impact on renal function has become increasingly recognized over time:

• Initially reported as rare (<1% in dose-escalating studies) 1
• Later studies showed more significant effects:
  • 7% of patients developed acute kidney injury
  • Mean decrease in glomerular filtration rate of 2.77 ml/min per 1.73 m² per year
  • 12% of patients developed chronic renal failure with long-term treatment 1
  • Increased risk of renal dysfunction (chronic kidney disease or acute kidney injury) with a pooled relative risk of 2.70 compared to other tyrosine kinase inhibitors 2

Mechanisms of Renal Injury

Imatinib can cause various forms of kidney damage:

• Acute tubular necrosis 1
• Tubular vacuolization 1
• Partial Fanconi syndrome (tubular dysfunction) 1, 3
• Thrombotic thrombocytopenic purpura 1
• Electrolyte disturbances (hypophosphatemia, hypokalemia, hypomagnesemia) due to increased urinary excretion 3

Risk Factors and Monitoring

The FDA label indicates that imatinib exposure increases in patients with renal impairment:

• 1.5 to 2-fold increase in mean exposure in patients with mild to moderate renal impairment 4
• Dose reductions are necessary for patients with moderate and severe renal impairment 4

Management Recommendations

1. For patients with existing renal impairment:

   • Maximum starting dose of 400 mg for patients with renal insufficiency 1
   • Dose reductions necessary for moderate and severe renal impairment 4
   • Renal function classification:
     • Mild: CrCL 40-59 mL/min
     • Moderate: CrCL 20-39 mL/min
     • Severe: CrCL <20 mL/min 4

2. For patients who develop renal impairment on imatinib:

   • Consider dose reduction or temporary interruption 1
   • Monitor and correct electrolyte disturbances 3
   • In severe cases, consider switching to a second-generation TKI 5
   • Some cases of renal failure are reversible upon discontinuation 1, 6

3. Monitoring recommendations:

   • Regular assessment of renal function during treatment
   • Monitor for electrolyte abnormalities, particularly phosphate, potassium, and magnesium 3
   • Early diagnosis and correction of electrolyte disorders can improve outcomes 3

Alternative TKI Options for Patients with Renal Concerns

• Nilotinib and dasatinib may be better options for patients with renal impairment:
  • Nilotinib-treated patients in phase I and II studies did not develop renal failure 1
  • Nilotinib has been reported to potentially benefit renal dysfunction through dissipation of fibrosis 1
  • Dasatinib administration has not led to worsening of renal function 1
  • Switching from imatinib to a second-generation TKI (nilotinib or dasatinib) showed significant improvement in renal function after just one month 5

Clinical Pearls

• Renal effects of imatinib may be underrecognized in clinical practice
• Early recognition of declining renal function or electrolyte abnormalities is crucial
• Some patients may require hemodialysis in severe cases 1
• Consider baseline renal function when selecting initial TKI therapy for CML patients
• Regular monitoring of renal function is advisable throughout imatinib treatment