Case Report of Near-Complete Remission of Relapsing Proteinuria Following GLP-1 Receptor Agonist Therapy in IgM-Positive Minimal Change Disease

Minimal change disease (MCD) with mesangial IgM deposition is an uncommon podocytopathy phenotype associated with frequent relapse and reduced responsiveness to corticosteroid therapy. Emerging evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert antiproteinuric and renoprotective effects beyond glycemic control, although data in non-diabetic glomerular disease remain limited. We report a case of a 34-year-old woman with relapsing proteinuria and edema 6 years after initial diagnosis of steroid-responsive MCD. Initial kidney biopsy demonstrated diffuse podocyte foot process effacement with mesangial IgM deposition, glomerulomegaly, and obesity-related glomerular features. At presentation to our center, body mass index was 36.9 kg/m 2 with urine albumin to creatinine ratio (UACR) of 2.7 g/g and preserved kidney function. The patient declined additional corticosteroid therapy because of prior steroid-associated weight gain. Partial improvement in proteinuria was achieved with losartan and empagliflozin; however, recurrent proteinuria persisted. Semaglutide therapy was later initiated and was temporally associated with substantial weight loss and marked reduction in proteinuria. Following transition to tirzepatide-based therapy, further weight reduction and continued improvement in proteinuria were observed, with UACR decreasing to <300 mg/g approximately 3.5 years after initial evaluation. This case highlights a possible association between GLP-1RA therapy, weight reduction, and improvement in proteinuria in IgM-positive MCD with obesity-related glomerular stress. Further studies are needed to clarify the role of GLP-1RAs in non-diabetic podocytopathies.