SAT-520 Tirzepatide-associated Interstitial Kidney Injury: A Case Report

Abstract Disclosure: M. Eldib: None. V. Mendpara: None. P. Rodriguez: None. J. Dhingra: None. L. Khan: None. Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for type 2 diabetes and obesity. They benefit glycemic control, cardiovascular risk reduction, and kidney protection. There have been reports of acute kidney injury associated to their use, which is noted in Warning and Precautions section of the FDA label. Although there are biopsy proven reports of Allergic Interstitial Nephritis with older GLP-1RA’s and Semaglutide, but there are no published report with Tirzepatide. Case Presentation: A 66-year-old man with type 2 diabetes, hypertension, chronic kidney disease, hyperlipidemia, obesity, osteoarthritis and GERD was on metformin (1000 mg twice daily), empagliflozin (10 mg daily), tirzepatide (10 mg weekly), lisinopril (10 mg daily), fenofibrate (160 mg daily) and pantoprazole (20 mg daily). He was prescribed Tirzepatide and remained on a stable regimen, receiving 5 mg for six months, followed by 7.5 mg for another six months. Serum creatinine (S. Cr) at the start of treatment with tirzepatide was 1.2. Over the course of the year, he achieved a notable weight reduction, decreasing from 135.6 kg to 121.6 kg. Dose increased to 10 mg after that for eight months. He presented during a diarrheal episode, during which serum creatinine was found to be elevated. A review of the past eight months revealed a gradual decline in kidney function, with S.Cr increasing from 1.1 to 2.11 mg/dL and eGFR decreasing from 68 to 34 mL/min/1.73 m². The endocrinologist discontinued metformin, Jardiance and increased tirzepatide to 12.5 mg when the kidney function worsened, while nephrology attributed the worsening renal function to dehydration from diarrhea in the context of underlying stage 3 CKD. Fenofibrate was stopped, pantoprazole had been self-discontinued and a kidney ultrasound showed normal parenchymal echogenicity. Despite these interventions, three months later, the S.Cr increased to 2.22 mg/dl. A kidney biopsy revealed chronic active tubulointerstitial nephritis with eosinophilic infiltrates and fibrosis. Tirzepatide was identified as the likely cause. It was discontinued and the patient was started on prednisone. This led to significant improvement in renal function. S.Cr decreased to 1.68 mg/dL after one month and stabilized at 1.78 mg/dL with an eGFR of 42 mL/min/1.73 m² after three months, down from a peak of 2.31. Discussion: This case highlights, biopsy-proven association between tirzepatide and chronic active tubulointerstitial nephritis. Also, it highlights the importance of recognizing potential adverse renal effects of incretin mimetic drugs. Prompt recognition, consideration of biopsy, cessation of the medication and appropriate management are critical to optimizing renal recovery. Presentation: Saturday, July 12, 2025