Is it safe to use Mounjaro (tirzepatide) with acute kidney injury?

Tirzepatide (Mounjaro) Should Not Be Used in Patients with Acute Kidney Injury

Tirzepatide (Mounjaro) should be discontinued in patients with acute kidney injury (AKI) due to the risk of worsening renal function and potential for adverse outcomes. 1

Risks of Tirzepatide in AKI

• The FDA label for Mounjaro (tirzepatide) specifically warns about the potential risk for worsening renal function in patients with renal impairment who experience severe gastrointestinal adverse reactions 1
• Patients with AKI are at increased risk for dehydration due to tirzepatide's gastrointestinal side effects, which can further compromise kidney function 1
• Tirzepatide can cause severe gastrointestinal adverse reactions including nausea, vomiting, and diarrhea, which can lead to fluid depletion and worsen AKI 1
• Recent case reports have documented acute kidney injury in patients taking tirzepatide, particularly when combined with other medications that affect volume status 2

Medication Management in AKI

• KDIGO guidelines recommend that patients with AKI receive potentially nephrotoxic medications only if absolutely necessary and only for as long as needed 3
• Drug stewardship is critical in AKI, with the primary goal of balancing the changing risks and benefits of drug utilization and dosing 3
• AKI represents a state of altered drug metabolism and clearance that can lead to unpredictable pharmacokinetics, especially with medications that affect fluid balance 4
• The risk-benefit ratio for medication use in AKI must be carefully considered and therapy personalized according to individual patient risks 3

Specific Concerns with Tirzepatide in AKI

• Tirzepatide can cause direct vasodilation, natriuresis, and reduction in extracellular volume, which can exacerbate AKI 2
• A recent study documented cases where tirzepatide contributed to symptomatic hypotension and acute kidney injury, requiring modification of other medications 2
• While tirzepatide itself does not require dose adjustment for chronic kidney disease, the FDA label specifically warns about monitoring renal function in patients with renal impairment who experience severe gastrointestinal adverse reactions 1
• The combination of rapid weight loss, volume depletion, and gastrointestinal side effects from tirzepatide creates a particularly high-risk situation for patients with AKI 5

Management Recommendations

• Discontinue tirzepatide in patients who develop AKI until kidney function has stabilized 1
• Monitor renal function closely if tirzepatide must be continued, with particular attention to signs of worsening kidney function 1
• Consider alternative diabetes management strategies during the acute phase of kidney injury 3
• Resume tirzepatide only after AKI has resolved and the patient is euvolemic 3, 1
• If tirzepatide is restarted after resolution of AKI, consider restarting at a lower dose with careful monitoring 5

Potential Benefits After AKI Resolution

• Once AKI has resolved, tirzepatide may offer renal benefits in patients with type 2 diabetes, as it has been shown to reduce urine albumin-to-creatinine ratio and slow eGFR decline compared to insulin glargine 6
• In patients without active AKI, tirzepatide has demonstrated a reassuring renal safety profile in clinical trials 7
• After recovery from AKI, the decision to restart tirzepatide should be based on a careful assessment of risks and benefits, with close monitoring of renal function 3

Remember that acute kidney injury represents a state of increased vulnerability where medication effects can be unpredictable and potentially harmful. The priority should be stabilizing kidney function before considering medications like tirzepatide that can affect fluid balance and potentially worsen kidney injury.