Semaglutide-Induced Severe AKI Requiring Hemodialysis

Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists, notable for their cardio and nephroprotective effects, are growing in popularity for the management of type 2 diabetes and obesity. We present a rare case of a patient with normal baseline renal function who developed severe acute kidney injury (AKI) with uremia requiring emergent dialysis shortly after starting semaglutide. Case Description: A 61-year-old female with type 2 diabetes, hypertension, and hyperlipidemia presents with a four week history of nausea, vomiting, diarrhea, and poor oral intake. Patient began semaglutide three months prior; other medications were unchanged. She has no known kidney disease. On arrival, she was lethargic and tremulous, but hemodynamically stable. Initial labs notable for sodium 129 mmol/L, potassium 2.9 mmol/L, bicarbonate 13 mmol/L, chloride 82 mmol/L, BUN 135 mg/dL, creatinine 14.2 mg/dL, eGFR 3 mL/min/1.73m2, magnesium 0.6 mmol/L, uric acid 26.8 mg/dL, and positive serum ketones. Imaging showed no acute pathology. Nephrology was consulted, recommending emergent hemodialysis (HD) and ICU admission. She was started on IV fluids, electrolyte repletion, and rasburicase. Nephrotoxic medications were held and she received DDAVP for bleeding at an IV site. After HD, labs trended towards optimal levels. Once improved she was transferred to the general floor and later discharged with nephrology follow-up. Discussion: GLP-1 receptor agonists enhance insulin secretion, reduce glucagon levels, and slow gastric emptying. Originally developed for diabetes, some have been recently approved for obesity. With the rise in use, closer examination of adverse effects is needed. While gastrointestinal effects are common, AKI remains rare, typically linked to dehydration. A post hoc analysis of the STEP 1, 2, and 3 trials revealed that semaglutide did not worsen renal outcomes regardless of patients' baseline renal function.1 A meta-analysis of FDA data indicated liraglutide had the highest risk of AKI, followed by semaglutide.2 Our patient developed AKI with uremia without existing renal disease. Extensive workup ruled out other causes such as immunologic, obstruction, etc., suggesting the presentation was due to semaglutide.