Acute Interstitial Nephritis Due to Tirzepatide (Mounjara)

Background: Tirzepatide (T) is a gastric inhibitory polypeptide (GIP) and GLP-1 receptor agonist approved by the U.S. Food and Drug Administration for the treatment of obesity and type 2 diabetes in 2022. The reported spectrum of its renal SEs was thought to be limited to volume depletion following gastrointestinal upsets. In this case report, we add an intrinsic etiology to its renal SEs. Case: A 43-year-old woman was referred for recent fluid overload and an increase in serum creatinine from baseline at 330 umol/L to 740 umol/L. She had type II diabetes mellitus as well as stable and chronic renal failure, which is clinically compatible with diabetic glomerulosclerosis. She did not have other previous medical illness or chronic intake of other medications. However, she admitted to taking Tirzepatide (Mounjara) for weight reduction 1 month prior to her recent admission. Her kidney biopsy showed acute interstitial nephritis on top of diffuse diabetic glomerulosclerosis. Serum complements, ANA, ANCA, protein electrophoresis, IgG4 level, hepatitis B, and C serology were within normal levels. T was discontinued, and she was treated with Mycophenolate mofetil (MMF) 1 g twice daily. To hasten the immunologic response without disturbing her diabetic management, an initial Prednisone 60 mg/day was given for 3 days. By 2 weeks, serum creatinine had improved to her previous baseline and did not require furosemide for fluid overload. By 6 weeks, MMF was discontinued, and she remained stable for 1 year. Conclusion: In genetically predisposed patients, acute interstitial nephritis can be triggered following T-use, yet it is amenable to drug-discontinuation and 6-week therapy with MMF.