B ZAHOROWSKA1, S D ROGER2
1Liverpool Hospital, Liverpool, New South Wales, 2Gosford Hospital, Gosford, New South Wales
Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been available in Australia for 4 years as sole therapy or in combination therapy for type 2 diabetic patients with insufficient glycaemic control. SGLT2 inhibitors act by blocking glucose uptake by renal proximal tubular epithelial cells thus promoting glycosuria. To date, investigation into further effects of SGLT2 inhibitors has been performed in experimental animal diabetes models and in vitro human proximal tubular cell lines.
Case Report: We report the first known case of renal tubular epithelial cell isometric vacuolation associated with SGLT2 inhibitor use. A 56 year old female presented with acute kidney injury, creatinine increased from 75µmol/L in January 2016 to 130µmol/L in December 2016. Her background included recent diagnosis of type 2 diabetes mellitus and hypertension in August 2016 and hyperlipidaemia. She had been commenced on dapagliflozin and metformin hydrochloride (5mg/1000mg) daily alongside perindopril 5mg and pre-existing rosuvastatin 5mg daily. Investigations demonstrated normal sized kidneys and a bland urine sediment, only the expected glycosuria. Renal biopsy demonstrated acute tubular damage and fine isometric type vacuolation in tubular lining epithelial cells on light microscopy with membrane bound vacuoles of different sizes on electron microscopy. These changes cleared 3 months post drug cessation, but were replaced by an infiltrate with lymphocytes and eosinophils. Creatinine failed to improve post cessation of SGLT2 inhibitor.
Conclusions: The renal biopsy findings are suggestive of drug induced injury with proposed mechanism of dapagliflozin inducing an osmotic nephrosis, possibly secondary to carbohydrate malabsorption as has been previously described in a canagliflozin rat model. These new findings require further investigation particularly due to limited human renal biopsy data associated with SGLT2 inhibitors.