Should Farxiga (dapagliflozin) be held in patients with Acute Kidney Injury (AKI)?

Management of Farxiga (Dapagliflozin) During Acute Kidney Injury

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

Rationale for Holding Farxiga in AKI

SGLT2 inhibitors like dapagliflozin are generally beneficial for long-term kidney outcomes, but require special consideration during episodes of acute kidney injury:

• The KDOQI guidelines recommend implementing "sick day protocols" which include holding SGLT2 inhibitors during acute illness, particularly when accompanied by volume depletion 1
• Kidney International guidelines recommend temporary discontinuation of medications affecting the renin-angiotensin system during AKI until renal function has returned to baseline or stabilized 2
• While SGLT2 inhibitors typically cause an initial "eGFR dip" of 3-5 mL/min/1.73 m² within the first 4 weeks of therapy, this is usually reversible and part of their normal mechanism of action 1

Mechanism of Concern

The concern with continuing Farxiga during AKI stems from several factors:

• SGLT2 inhibitors have diuretic and natriuretic effects that could potentially worsen volume depletion in the setting of AKI 1
• Patients with AKI may have compromised renal perfusion, and the hemodynamic effects of SGLT2 inhibitors could theoretically exacerbate this situation
• Case reports have identified AKI in patients on SGLT2 inhibitors, particularly when combined with other nephrotoxic agents or during acute medical events 3

When to Restart Farxiga After AKI

After AKI resolution:

1. Wait until renal function has returned to baseline or stabilized
2. Ensure adequate volume status and blood pressure
3. Consider starting at a lower dose than previously used
4. Monitor renal function and potassium within 2-4 weeks after restarting
5. A small rise in serum creatinine (10-20%) is acceptable when restarting 2

Special Considerations

Risk Factors for AKI with SGLT2 Inhibitors

• Concomitant use of renin-angiotensin system blockers (ACEIs/ARBs) 3
• Exposure to other nephrotoxic agents (contrast media, NSAIDs, COX-2 inhibitors) 3
• Acute medical events (diarrhea, sepsis, dehydration) 3
• Baseline decreased glomerular filtration rate 3

Evidence Supporting Safety

Despite concerns about AKI, evidence from clinical trials is reassuring:

• In the DAPA-CKD trial, dapagliflozin actually reduced the risk of abrupt declines in kidney function (HR 0.68 [95% CI 0.49,0.94]) compared to placebo 4
• Acute kidney injury-related serious adverse events were not significantly different between dapagliflozin and placebo groups (2.5% vs 3.2%) 4
• A randomized study of dapagliflozin in acute decompensated heart failure showed no increase in AKI episodes compared to control (13% vs 9.4%, p=0.45) 5

Practical Approach

1. Identify AKI: Recognize rising creatinine or declining eGFR
2. Hold Farxiga: Temporarily discontinue during the acute phase of AKI
3. Address underlying causes: Treat the primary cause of AKI
4. Monitor renal function: Follow creatinine and eGFR until stabilization
5. Restart when appropriate: Resume once renal function returns to baseline or stabilizes

Common Pitfalls to Avoid

• Don't confuse the initial "eGFR dip" (3-5 mL/min/1.73 m²) that occurs within the first 4 weeks of starting SGLT2 inhibitors with true AKI 1
• Don't permanently discontinue Farxiga after AKI resolution if the patient would otherwise benefit from its cardiorenal protective effects
• Don't restart too early before renal function has stabilized or returned to baseline
• Don't overlook other nephrotoxic medications that may be contributing to AKI

By following these guidelines, clinicians can appropriately manage Farxiga during episodes of AKI while preserving its long-term benefits for kidney and cardiovascular outcomes.