Case Presentation: A 69-year-old male with T2DM, OSA, and chronic back pain presented to the ED with nausea, vomiting, malaise, and confusion. He had been on metformin for diabetes, and 6 days prior to presentation, was switched to Victoza (Liraglutide) for better glucose control. He lived at home with his wife, who noticed that his oral intake had been decreasing and he had not urinated in about 3 days prior to presentation. She noted tremors and confusion, causing him to not recognize her at some points. His labs were notable for new renal failure with BUN 73 mg/dL, Cr 10 mg/dL, CO2 21 mmol/L, anion gap 30, Lactic acid 3.5 mmol/L. His baseline Cr was 1.3 mg/dL and GFR 55 mL/min/BSA. Per his PCP, last normal basic metabolic panel was less than 1 month prior to presentation. A renal ultrasound revealed no urine retention, hydronephrosis, or nephrolithiasis. A urine sample was notable for muddy brown casts, consistent with acute tubular necrosis (ATN). He was started on fluids to assess renal response. Unfortunately, given his altered mental status and unresponsive renal function, he was started on dialysis the next day. His mental status improved shortly after. He remained on dialysis for nearly 4 months prior to returning to his baseline kidney function, where he has remained.
Discussion: Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the small intestine that increases the post-prandial insulin release by acting on its receptors in the pancreas, however it has also been demonstrated to have extrapancreatic effects (1). In particular, GLP-1 has been studied to have its effect on blood pressure, renal blood flow, diuresis, and natriuresis, with human and animal models demonstrating the localized expression of GLP-1 receptors in the kidney (9-14). Unfortunately, the exact mechanism of the renal effects of GLP-1 is poorly understood. The use of GLP-1 agonists, a class of antidiabetic drug including exenatide and liraglutide, has been associated with acute kidney injury (AKI). Many case reports on AKI secondary to the use of exenatide have demonstrated pre-renal injury, with a significant portion of patients on medications that inhibit renal-angiotensin system. Some reports of acute interstitial nephritis that improved with steroid treatment have been reported as well. To our knowledge, only 3 case reports on AKI secondary to liraglutide have been published (6). The existing cases have been associated with acute tubular necrosis along with GI side effects, requiring immediate discontinuation of the drug, volume repletion and even hemodialysis. In our patient, who initially presented in the setting of significant GI symptoms as well as AKI in the setting of recent initiation of Victoza (liraglutide), ATN was evident on urine microscopy study. ATN likely developed from prolonged pre-renal/hypoperfusive injury in the setting of volume contraction due to GI symptoms, as demonstrated in other case reports. Furthermore, although less studied, especially in clinical settings, the intrinsic effect of GLP-1 receptor activation on the renal vasculature likely contributed to the renal injury induced by the drug.
Conclusions: The purpose of this abstract is to recognize poorly documented but potentially serious side effects of Liraglutide.