Semaglutide-Associated Minimal Change Disease: A Potential Rare Complication of a Novel Medication

Introduction: Glucagon-like peptide 1 receptor agonists (GLP1-RAs) are a class of antihyperglycemic medications that have demonstrated benefits for obesity and cardio-renal protection. The increased utilization of these therapies may reveal previously undocumented adverse effects. Case Description: An 83-year-old male with CKD (baseline Cr 1.7), hypertension, hyperlipidemia, congestive heart failure, hypothyroidism, and obesity (BMI 33) presented to the hospital with 5 days of dyspnea and bilateral leg swelling. He was recently started on Semaglutide in Israel. The patient reports no use of NSAIDs or over-the-counter medications. On exam, he had diminished breath sounds at the lung bases and 2+ bilateral lower extremity pitting edema. Labs showed BUN 34mg/dL, creatinine 2.06mg/dL, and albumin of 2.2g/dL. He had a total serum cholesterol level of 213 mg/dL and triglyceride of 170mg/dL. Urinalysis had 4+ proteinuria. The urinary protein to creatinine ratio (UPCR) was 17.2g/g. Serologic testing of ANCA-ab, ANA, GBM-ab, PLAR2R-ab were all negative. HIV, viral hepatitis, and renal ultrasound studies were unremarkable. A renal biopsy was performed, and light microscopy revealed global glomerulosclerosis. Electron microscopy showed complete visceral epithelial cell foot process effacement, which was consistent with minimal change disease (Figure 1). He was treated with pulse solumedrol for 3 days and transitioned to a 3-month prednisone taper. The patient also received 2 doses of Rituximab during the admission. UPCR improved from 17.2g/g to 9.2g/g. His creatine peaked at 4.1mg/dL and improved to 3.2mg/dL at discharge. Discussion: Podocytopathies can be associated with certain medications (i.e. NSAIDS, lithium, interferon), but their link with GLP-RAs has not been well described. Therefore, new edema or proteinuria associated with GLP1-RA initiation should prompt investigation for glomerular disease and discontinuation of the medication.Figure 1