Should colchicine be held in acute kidney injury (AKI)?

From the Guidelines

Yes, you should hold colchicine in acute kidney injury (AKI). Colchicine is primarily eliminated by the kidneys, and its clearance is significantly reduced when kidney function declines. In AKI, continuing colchicine can lead to toxic accumulation of the drug, resulting in serious adverse effects including neuromuscular toxicity, gastrointestinal symptoms, bone marrow suppression, and in severe cases, multi-organ failure. The risk of toxicity is particularly high because colchicine has a narrow therapeutic window, meaning the difference between therapeutic and toxic doses is small. Key points to consider:

• Colchicine toxicity can occur in patients with renal impairment, as stated in the European Heart Journal study 1.
• The 2016 updated EULAR evidence-based recommendations for the management of gout suggest that colchicine should be avoided in patients with severe renal impairment and that the dose should be reduced in patients with renal impairment 1.
• If you're using colchicine for conditions like gout or familial Mediterranean fever, consider alternative treatments during the AKI episode. For acute gout, NSAIDs may be used if not contraindicated, or corticosteroids might be appropriate.
• Resume colchicine only after kidney function has recovered and with appropriate dose adjustments based on the new baseline kidney function. Always consult with a healthcare provider before making any medication changes.

From the FDA Drug Label

Colchicine dosing must be individualized according to the patient's renal function [see Use in Specific Populations (8.6)] For prophylaxis of gout flares in patients with mild (estimated creatinine clearance [Cl cr] 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, the starting dose should be 0.3 mg/day and any increase in dose should be done with close monitoring.

Dose adjustment is necessary in severe renal impairment.

• For patients with severe renal impairment, the starting dose should be 0.3 mg/day.
• For patients undergoing dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring.
• Close monitoring is required for patients with renal impairment.

Acute kidney injury (AKI) is not explicitly addressed, but given the need for dose adjustment in severe renal impairment, it is reasonable to exercise caution and consider holding or adjusting the dose of colchicine in patients with AKI until renal function improves. 2

From the Research

Colchicine Use in Acute Kidney Injury (AKI)

• Colchicine is a medication used to treat gout and familial Mediterranean fever, but its use in patients with acute kidney injury (AKI) is a concern due to the risk of toxicity 3, 4.
• Studies have shown that colchicine toxicity is increased in patients with chronic kidney disease (CKD) and AKI, and dosage reduction is required based on the level of kidney function 3, 5.
• A case report of a patient with polyarticular gout who developed acute renal failure after taking an accidental overdose of colchicine highlights the risk of colchicine-induced nephrotoxicity 5.
• The Cochrane Review of colchicine for acute gout found that low-dose colchicine may be an effective treatment for acute gout, but the evidence is limited by the small number of studies and the risk of bias 6, 7.
• The review also found that high-dose colchicine is associated with a greater risk of adverse events, including diarrhea, vomiting, and nausea, compared to low-dose colchicine or placebo 6, 7.

Recommendations for Colchicine Use in AKI

• Based on the available evidence, it is recommended that colchicine be used with caution in patients with AKI, and the dosage should be reduced based on the level of kidney function 3, 5.
• Low-dose colchicine may be a preferred treatment option for acute gout in patients with AKI, due to the lower risk of adverse events compared to high-dose colchicine 6, 7.
• However, the decision to use colchicine in patients with AKI should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 3, 4.