Abstract: PUB073
Tirzepatide: Pillar of Diabetic Kidney Disease Therapy or Wrecking Ball?
Session Information
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Linder, Ashley, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Bergeron, Jennifer, West Virginia University School of Medicine, Morgantown, West Virginia, United States
Introduction
The emerging standard of diabetic kidney disease mangement is combination therapy of renin-angiotensin system inhibitors, non-steroidal mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists (GLP-1RAs). As clinical outcomes with triple or quadruple therapy are considered, we present a case of acute tubular injury that calls into question if tirzepatide is as renal protective as it is touted.
Case Description
A 54-year-old male with CKD3b after prior IgA Vasculitis (IgAV) with complete remission, insulin dependent type 2 diabetes with mild diabetic changes on biopsy, HTN, and class I obesity presented for CKD follow up. He was on losartan and empagliflozin with good blood pressure and stable CKD (Cr 2.5mg/dl, eGFR 35), but his A1c was 7.9, so he was started on tirzepatide for renal triple therapy and uptitrated per label.
Unfortunately, his creatinine and cystatin C steadily rose the next 4 months to 3.4mg/dL (eGFR 20) and 3.3mg/L (eGFR 16). He reported good intake, no GI symptoms, had stable weight and blood pressure (130s/70s), and no symptoms/signs of dehydration or hypovolemia. There were no diuretics, new medications, or exposure to any nephrotoxins. His A1c was 7.1. His urine protein was undetectably low without hematuria. Repeat kidney biopsy found significant acute tubular injury not accounted for by his mild diabetic changes (RPS I-II) and his continued remission of his IgAV. After discussion with the pathologist, his tirzepatide was held, and his kidney function returned to baseline (see image).
Discussion
AKI caused by GLP-1RAs is generally due to the drug’s GI side effects but this case tells a different story. To our knowledge, this is the first report of a GLP-1RA causing biopsy proven intrinsic acute tubular injury during the initiation of combination therapy. While studies have shown improved CKD outcomes for GLP-1RAs, combination therapy has not been fully studied and this case shows that more might not always be better.