Do I need to discontinue Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors during Acute Kidney Injury (AKI)?

Yes, Discontinue SGLT2 Inhibitors During Acute Kidney Injury

SGLT2 inhibitors should be temporarily discontinued during acute kidney injury and other acute illness states that predispose to volume depletion or metabolic complications. 1, 2

Guideline-Based Recommendations for Discontinuation

When to Withhold SGLT2 Inhibitors

The KDIGO 2022 guidelines explicitly state it is reasonable to withhold SGLT2 inhibitors during:

• Critical medical illness when patients are at greater risk for ketosis 1
• Prolonged fasting or reduced oral intake 1, 2
• Surgery requiring bowel preparation or extended hospitalization 1
• Acute illness with fluid losses (such as gastrointestinal illness or excessive heat exposure) 2

FDA Drug Label Warnings

The empagliflozin (Jardiance) FDA label provides specific guidance:

• Consider temporarily discontinuing SGLT2 inhibitors in clinical situations known to predispose to ketoacidosis, including prolonged fasting due to acute illness or surgery 2
• Discontinue promptly if acute kidney injury occurs and institute appropriate treatment 2
• Monitor patients for signs and symptoms of acute kidney injury in any setting of reduced oral intake or fluid losses 2

Physiologic Rationale for Discontinuation During AKI

Volume Depletion Risk

• SGLT2 inhibitors cause intravascular volume contraction through osmotic diuresis 2
• Patients with AKI are often hypovolemic and more susceptible to further renal function deterioration 2
• The combination of AKI and SGLT2 inhibitor-induced volume depletion can worsen kidney injury 2

Ketoacidosis Risk

• Acute illness and reduced oral intake predispose to euglycemic diabetic ketoacidosis, a serious complication of SGLT2 inhibitors 2
• AKI often occurs in the context of acute illness, surgery, or reduced intake—all situations that increase ketoacidosis risk 1, 2

When to Resume SGLT2 Inhibitors

Restart Criteria

• Resume SGLT2 inhibitors only after the patient is eating and drinking normally 1
• Ensure complete resolution of the acute illness that precipitated the AKI 2
• Confirm adequate volume status and hemodynamic stability 1
• Verify kidney function has stabilized or improved 2

Long-Term Continuation After Recovery

• Once restarted following AKI recovery, SGLT2 inhibitors can be continued even if eGFR subsequently falls below 20 mL/min/1.73 m², unless kidney replacement therapy is initiated 1
• A reversible decrease in eGFR with SGLT2 inhibitor use is generally not an indication to discontinue therapy in stable chronic kidney disease 1

Distinguishing Acute from Chronic eGFR Changes

Do NOT Discontinue for Chronic Stable Use

• The initial mild decline in eGFR after starting SGLT2 inhibitors reflects hemodynamic changes (reduced intraglomerular pressure via tubuloglomerular feedback) and is not true AKI 1, 3
• This functional decline is expected and beneficial for long-term kidney protection 1

DO Discontinue for Acute Illness

• The key distinction is acute illness context: discontinue during AKI, acute illness, surgery, or volume depletion states 1, 2
• The concern is not the medication's chronic effects on eGFR, but rather the acute risk of worsening kidney injury and ketoacidosis during illness 2

Evidence on SGLT2 Inhibitors and AKI Risk

Protective Effects in Stable Patients

• Large randomized trials demonstrate SGLT2 inhibitors actually reduce the risk of AKI in stable patients with diabetes and CKD 4, 3, 5
• Real-world data show no increased AKI risk compared to other glucose-lowering drugs in stable outpatient settings 6, 5

Risk During Acute Illness

• Despite protective effects in stable patients, the FDA issued warnings about AKI risk in the context of volume depletion and acute illness 2, 7
• Pharmacovigilance data identified AKI cases, particularly with canagliflozin, with median onset at 72 days and hospitalization rate of 63.5% 7

Common Pitfalls and Caveats

• Do not confuse the expected initial eGFR dip with AKI: the former is hemodynamic and beneficial; the latter requires discontinuation 1, 3
• Do not continue SGLT2 inhibitors during acute illness "because they're kidney protective": the protection applies to chronic stable use, not acute illness states 1, 2
• Reduce concomitant diuretics before initiating SGLT2 inhibitors in patients at risk for volume depletion 1
• Educate patients about "sick day protocols": temporarily withhold during illness, maintain hydration, and seek medical attention early 1
• Monitor for ketoacidosis even with normal glucose levels: SGLT2 inhibitors can cause euglycemic ketoacidosis, particularly during acute illness 2