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Kidney Week

Abstract: FR-PO060

AKI with Proximal Tubular Epithelium Vacuolization following SGLT2 Inhibitor Overdose

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

  • Araki, Makoto, Sapporo Tokushukai Hospital, Sapporo, Japan
  • Ogawa, Yayoi, Sapporo Tokushukai Hospital, Sapporo, Japan
  • Yanai, Mitsuru, Sapporo Tokushukai Hospital, Sapporo, Japan
Introduction

Sodium-glucose cotransporter-2 inhibitors (SGLT2i), commonly used to treat diabetes, heart failure, and chronic kidney disease, have been occasionally linked to acute kidney injury (AKI). Although osmotic renal injury is suspected to be one of the causes due to the drug’s pharmacological effects, there are few histological studies on this issue.

Case Description

A 76-year-old woman with a history of two prior suicide attempts through drug overdose was admitted to our hospital after ingesting a large dose of her husband’s medications an hour before arrival. The medications included 160 mg of esomeprazole, 1740 mg of azosemide, 725 mg of eplerenone, and 290 mg of dapagliflozin. She had diabetes, an HbA1c level of 8.1%, and bipolar disorder, but her family carefully managed her medications to prevent overdose. Following admission, diuretic-induced polyuria exceeded 150 mL/h. Ten hours later, a drop in blood pressure and signs of dehydration prompted an increase in fluid infusion. On the second day, her urine output increased to 5 liters per day, but then decreased sharply. By the fourth day, she became anuric. Subsequently, she remained anuric with her creatinine level rising to 4.12 mg/dl, leading to a diagnosis of stage 3 AKI and the initiation of dialysis. A renal biopsy conducted the following day revealed significant vacuolization and swelling in the proximal tubular cells, confirming osmotic tubular damage likely caused by SGLT2i, given the absence of hyperosmotic agents or severe potassium imbalance. Fortunately, her urine output gradually improved from the sixth day, allowing for the cessation of dialysis. Her renal function normalized by the twelfth day, and she was subsequently transferred for psychiatric care on the eighteenth day.

Discussion

Osmotic tubular injury, characterized by diffuse vacuolization and swelling of proximal tubular cells and traditionally associated with hyperosmotic agents, is now also sporadically reported with the use of SGLT2i. Risk factors include chronic kidney disease, advanced age, dehydration, and diuretic use. In this case, a combination of uncontrolled hyperglycemia, diuretic-induced dehydration, and high-dose SGLT2i likely caused the tubular injury. The prognosis for SGLT2i-induced damage remains uncertain, though it was favorable here.