What are the considerations for using semaglutide (glucagon-like peptide-1 receptor agonist) in patients with Acute Kidney Injury (AKI) or impaired renal function?

Semaglutide Use in Acute Kidney Injury: Safety Considerations and Management

Semaglutide should be used with caution in patients with acute kidney injury (AKI), with close monitoring of renal function and hydration status, particularly in patients experiencing gastrointestinal side effects. 1, 2

Safety Concerns and Contraindications

• The FDA label specifically warns about postmarketing reports of acute kidney injury and worsening of chronic renal failure in patients treated with GLP-1 receptor agonists, which may sometimes require hemodialysis 2
• Most reported kidney injury events occurred in patients who experienced nausea, vomiting, diarrhea, or dehydration, which are common side effects of semaglutide 2, 1
• Case reports have documented acute interstitial nephritis and worsening kidney function in patients taking semaglutide, including in those with previously normal kidney function 3, 4
• While exenatide and lixisenatide are contraindicated in severe renal impairment or end-stage renal disease (ESRD), semaglutide should be used with caution in these populations 5

Clinical Approach to Using Semaglutide in AKI

Assessment and Monitoring

• Monitor renal function when initiating or escalating doses of semaglutide in patients reporting severe adverse gastrointestinal reactions 2
• Evaluate volume status carefully, as both hypovolemia and hypervolemia can complicate AKI management 1
• Pay particular attention to patients experiencing gastrointestinal side effects such as nausea, vomiting, and diarrhea, as these increase dehydration risk and can worsen AKI 1, 2

Dosing Considerations

• For patients recovering from AKI, consider reintroducing semaglutide at a lower dose with gradual titration once renal function stabilizes 1
• Renal impairment does not impact the pharmacokinetics of semaglutide in a clinically relevant manner, according to FDA data from studies with single doses in patients with different degrees of renal impairment 2

Glycemic Control in AKI

• Maintain serum glucose levels between 140-180 mg/dl in hospitalized patients with AKI 5
• Tight glucose control (80-110 mg/dl) should not be pursued due to increased risk of hypoglycemia in patients with kidney dysfunction 5
• Semaglutide is unlikely to cause hypoglycemia on its own but may do so when used with insulin or insulin secretagogues; consider reducing doses of these medications when used concomitantly 5

Potential Benefits vs. Risks

• In the SUSTAIN trials, semaglutide was associated with initial reductions in eGFR that plateaued over time and marked reductions in urinary albumin-to-creatinine ratio (UACR) 6
• Semaglutide was associated with a 36% reduction in the risk of persistent macroalbuminuria in patients with type 2 diabetes 1
• However, case reports have documented acute kidney injury in patients taking semaglutide, with some requiring hemodialysis 7, 3, 4
• A retrospective study of patients with advanced CKD (stage 4 or greater) found that most tolerated semaglutide despite gastrointestinal side effects, with improvements in glycemic control 8

Practical Recommendations

• Ensure adequate hydration in patients on semaglutide, especially those with AKI 1
• If AKI occurs while on semaglutide, particularly with gastrointestinal symptoms, discontinue the medication and provide appropriate management 7
• Laboratory monitoring should be more frequent when initiating semaglutide in patients with AKI or at risk for AKI 2, 1
• Consider the risk-benefit profile carefully in patients with moderate to severe kidney disease due to limited kidney reserve in the event of an adverse kidney event 7

Common Pitfalls and Caveats

• Failing to recognize the connection between gastrointestinal side effects, dehydration, and worsening kidney function 2, 7
• Not adjusting other glucose-lowering medications when using semaglutide in AKI patients, increasing hypoglycemia risk 5
• Overlooking the possibility of semaglutide-associated acute interstitial nephritis, which has been reported in case studies 3, 4
• Continuing semaglutide despite worsening kidney function or significant gastrointestinal symptoms 2, 7