Should Mounjaro (tirzepatide) be held in patients with Acute Kidney Injury (AKI)?

Management of Tirzepatide (Mounjaro) in Acute Kidney Injury

Tirzepatide (Mounjaro) should be temporarily discontinued in patients with acute kidney injury until renal function has returned to baseline or stabilized.

Rationale for Holding Tirzepatide in AKI

Tirzepatide requires special consideration during episodes of acute kidney injury for several important reasons:

• The FDA label for Mounjaro specifically recommends monitoring renal function in patients with renal impairment who experience severe adverse gastrointestinal reactions 1
• Gastrointestinal adverse effects of tirzepatide (nausea, vomiting, diarrhea) can worsen volume depletion, potentially exacerbating AKI 1
• KDIGO guidelines recommend temporary discontinuation of potentially nephrotoxic and renally excreted drugs in people with serious intercurrent illness that increases the risk of AKI 2
• Case reports have documented AKI associated with GLP-1 receptor agonists, including tirzepatide 3

Management Algorithm for Tirzepatide in AKI

1. Immediately discontinue tirzepatide when AKI is diagnosed

   • This follows the KDIGO consensus statement that drug selection, dosing, and monitoring among patients with AKD should be guided by the functional phase, trajectory, and stage of AKD 2

2. Provide supportive care for AKI

   • Ensure adequate hydration with isotonic fluids
   • Avoid other nephrotoxic medications
   • Monitor electrolytes, particularly potassium and bicarbonate

3. Monitor renal function

   • Follow creatinine, BUN, and eGFR closely
   • Assess for signs of recovery

4. Considerations for restarting tirzepatide after AKI resolution:

   • Wait until renal function has returned to baseline or stabilized
   • Ensure adequate volume status before restarting
   • Consider starting at a lower dose than previously used
   • Monitor renal function within 2-4 weeks after restarting 4

Special Considerations

Pharmacokinetics in Renal Impairment

While pharmacokinetic studies suggest tirzepatide exposure is generally similar across renal impairment groups 5, this does not negate the need to hold the medication during acute kidney injury when rapid changes in renal function are occurring.

Risk of Worsening AKI

The KDIGO guidelines emphasize that "the decision to discontinue, introduce and/or reintroduce medications in patients with AKD should be individualized" with considerations including "potential for nephrotoxicity" and "effect of AKD on metabolites" 2. The diuretic and natriuretic effects of tirzepatide could potentially worsen volume depletion in the setting of AKI 4.

Long-term Renal Benefits vs. Short-term Risks

While tirzepatide may have positive long-term impacts on UACR without detrimental effects on eGFR 6, this does not outweigh the potential risks during an acute kidney injury episode.

Common Pitfalls to Avoid

1. Continuing tirzepatide despite AKI: This could worsen volume depletion through GI side effects and diuretic properties.

2. Restarting too soon: Ensure renal function has stabilized before reintroducing tirzepatide.

3. Failing to monitor: Close monitoring of renal function is essential when restarting tirzepatide after an AKI episode.

4. Overlooking other nephrotoxic medications: KDIGO recommends avoiding combinations of nephrotoxic medications in patients with AKD 2.

By temporarily discontinuing tirzepatide during AKI and following a careful protocol for reintroduction after recovery, clinicians can minimize risks while preserving the long-term benefits of this medication for patients with type 2 diabetes.