GLP-1 Receptor Agonist-Associated Minimal Change Disease: Emerging Adverse Effect?

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained popularity in recent years due to their effectiveness in glycemic control, weight loss, cardiovascular protection, and kidney protection. We report a case of biopsy-proven minimal change disease (MCD) associated with GLP-1 RA use. Case Description: A 48-year-old female with no known medical history presented with a one-week history of worsening generalized peripheral edema and facial swelling. She reported a weight gain of over 10 pounds during that time. Rest of the review of system was negative. Notably, she had started semaglutide approximately six months prior for weight loss. Initial labs showed normal renal function (creatinine 0.9 mg/dL) and no significant electrolyte abnormalities 24 hour urine protein was 11 g. Serological workup was negative. Renal USG was unremarkable. Kidney biopsy revealed normal appearing glomeruli on light microscopy, no immune or complement deposits on immunofluorescence and electron microscopy with diffuse podocyte foot process effacement (~70%) consistent with minimal change disease. The patient was started on glucocorticoids and semaglutide was discontinued. At 6-week follow-up, urine protein-creatinine ratio had improved to 0.28 g/g, and her symptoms had significantly improved. A steroid taper was initiated. Discussion: Our literature review revealed a few case reports of MCD associated with GLP-1 RA use, particularly semaglutide. Patients typically present with nephrotic syndrome and biopsy findings, at ultrastructural examination, consistent with diffuse podocytopathy. Similar to our case, previously reported case showed temporal association of 3 – 6 months after GLP-1 RA initiation. Most responded well to glucocorticoids and discontinuation of the agent. One proposed mechanism involves immune modulation by GLP-1 RAs potentially triggering autoimmunity with possibly induction of formation of anti nephrin antibodies. Whether this adverse effect is unique to semaglutide or shared by other GLP-1 RAs remains unclear. As the use of GLP-1 RAs continues to rise, it is essential to recognize and report potential adverse effects to better understand their mechanisms and develop preventive strategies. We present this case of MCD temporally associated with recent GLP-1 RA initiation.