Can Empagliflozin (Jardiance) be given in patients with Acute Kidney Injury (AKI)?

From the Guidelines

Empagliflozin (Jardiance) should not be initiated in patients with Acute Kidney Injury (AKI), but it can be continued in patients who develop AKI while already on the medication.

Rationale

• The evidence from 1 suggests that SGLT2 inhibitors, such as empagliflozin, can be continued in patients who develop a decline in eGFR, including those with AKI, as long as the patient is tolerating the treatment and not requiring kidney replacement therapy (KRT).
• However, the same evidence also notes that SGLT2 inhibitors should be held during illness, which may include AKI, to prevent volume depletion and other complications.
• The study in 1 discusses the risk of AKI with SGLT2 inhibitors, but notes that randomized clinical outcome trials have not found an increased risk of AKI with these medications, even when combined with diuretics or other medications that reduce glomerular filtration.
• It is essential to monitor patients with AKI closely for signs of volume depletion, hypoglycemia, and other complications, and to adjust the treatment plan as needed.
• The evidence suggests that the benefits of continuing empagliflozin in patients with AKI may outweigh the risks, but this decision should be made on a case-by-case basis, taking into account the individual patient's condition and medical history.

Key Considerations

• Monitor patients with AKI closely for signs of volume depletion, hypoglycemia, and other complications.
• Adjust the treatment plan as needed to prevent these complications.
• Consider holding empagliflozin during illness, including AKI, to prevent volume depletion and other complications.
• Continue empagliflozin in patients who develop AKI while already on the medication, as long as the patient is tolerating the treatment and not requiring KRT.

From the FDA Drug Label

JARDIANCE can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine [see Adverse Reactions (6. 1)]. There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including JARDIANCE. Patients with impaired renal function (eGFR less than 60 mL/min/1. 73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating JARDIANCE in patients with one or more of these characteristics, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating JARDIANCE. Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy.

Empagliflozin (Jardiance) should not be initiated in patients with Acute Kidney Injury (AKI).

• The drug label warns of the risk of acute kidney injury with JARDIANCE use.
• It is recommended to assess volume status and renal function before initiating JARDIANCE, and to correct any volume depletion before starting the medication.
• Patients with impaired renal function are at increased risk for volume depletion or hypotension. 2

From the Research

Empagliflozin and Acute Kidney Injury (AKI)

• Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been associated with a potential risk of AKI, particularly in patients with type 2 diabetes mellitus (T2DM) who are also taking renin-angiotensin-aldosterone system blockers or other nephrotoxic agents 3.
• However, a real-world study found that empagliflozin users were at a lower risk of developing AKI compared to linagliptin users, with a 40% lower risk of AKI (adjusted hazard ratio, 0.60; 95% confidence interval, 0.45-0.82, p = 0.001) 4.
• There have been reports of biopsy-proven acute interstitial nephritis (AIN) secondary to empagliflozin, which resolved with discontinuation of the medication and corticosteroid treatment 5.

Renoprotective Effects of Empagliflozin

• Empagliflozin has been shown to protect against renal ischemia/reperfusion injury in mice, with decreased serum levels of creatinine and urea, reduced tubular damage, and inhibited apoptosis in injured kidneys 6.
• Empagliflozin has also been found to attenuate AKI after myocardial infarction in diabetic rats, with improved hyperglycemia, increased blood β-hydroxybutyrate level, and suppressed expression of injury markers 7.

Clinical Considerations

• While empagliflozin may be associated with a risk of AKI in certain patients, the available evidence suggests that it may also have renoprotective effects, particularly in patients with T2DM.
• The decision to use empagliflozin 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, 5, 6, 7.