Abstract: FR-PO0736
Membranous Nephropathy Associated with Compounded Tirzepatide: Cause, Cure, or Coincidence
Session Information
- Glomerular Diseases: Membranous Nephropathy, FSGS, and Podocytopathies
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Agrawal, Vikas, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Yadlapalli, Srinath, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Ellis, Rebecca J., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Guo, Shunhua, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Doshi, Simit, Indiana University School of Medicine, Indianapolis, Indiana, United States
Introduction
Drug-induced membranous nephropathy (MN) is increasingly recognized, with implicated agents such as NSAIDs, gold salts, and checkpoint inhibitors. Tirzepatide, a dual GIP/GLP-1 agonist approved for type 2 diabetes and obesity, has shown renal benefits in clinical trials. Immune-mediated kidney injuries, predominantly acute interstitial nephritis (AIN), have been reported post-marketing. Compounded GLP-1 formulations have unpredictable effects due to variable composition and unregulated manufacturing.
Case Description
A 47-year-old female with no significant medical history presented with persistent proteinuria and bilateral lower extremity edema. Laboratory testing showed urine protein: creatinine ratio (UPCR) of 2.1 g/g, hypoalbuminemia (3.2 g/dL) and hyperlipidemia with preserved renal function and normoglycemia. Serologic workup was unremarkable. Her medications included compounded tirzepatide initiated approximately 18 months prior to presentation. She had transitioned to FDA-approved tirzepatide due to symptoms of edema that developed after 16 months of using the compounded formulation.
Kidney biopsy revealed subepithelial deposits, diffuse podocyte foot process effacement, and negative PLA2R staining. Mass spectrometry for alternative antigens was negative. Age-appropriate cancer screening was unremarkable.
Despite 6 months of conservative management, proteinuria worsened with peak ~ 4.3g/g. Lisinopril 2.5 mg was initiated, and rituximab therapy was planned. FDA-approved tirzepatide was resumed before immunosuppression (IS) initiation. Within two months of resuming therapy, UPCR improved to 0.5 g/g. IS was deferred.
Discussion
This case raises multiple diagnostic and therapeutic questions. Is this spontaneous remission of primary MN from a novel target antigen? Does the strong temporal association implicate compounded tirzepatide as the cause of secondary MN? Does prescription tirzepatide have potential immunomodulatory effects that could have lead to remission of MN?
Temporal relationship between compounded tirzepatide and disease activity suggests a drug-related process further supported by PLA2R negativity and the absence of other immune targets.
Although causality cannot be confirmed, this case underscores the need for pharmacovigilance distinguishing compounded from branded formulations. GLP-1 agents and their effect on immune function and glomerular disease need to be further studied.