Abstract: SA-PO286
Osmotic Nephrosis: SGLT2 Inhibitor (SGLT2-i) Leaves a Footprint Behind
Session Information
- Trainee Case Reports - VI
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 103 AKI: Mechanisms
Authors
- Kaushal, Amit, University of North Dakota School of Medicine, Fargo, North Dakota, United States
- Phadke, Gautam M., University of North Dakota School of Medicine, Fargo, North Dakota, United States
- Johnson, Richard J., University of Colorado Denver, Aurora, Colorado, United States
- Kukla, Aleksandra, Mayo Clinic , Rochester, Minnesota, United States
- Alexander, Mariam P., Mayo Clinic , Rochester, Minnesota, United States
- Hao, Weimin, University of North Dakota School of Medicine, Fargo, North Dakota, United States
- Lanaspa, Miguel A., University of Colorado Denver, Aurora, Colorado, United States
- Mahale, Adit S., University of North Dakota School of Medicine, Fargo, North Dakota, United States
Introduction
SGLT2-i causing acute kidney injury has been reported. Our case, defines the pathogenesis of severe AKI due to SGLT2-i. This class of medications cause functional reduction in GFR by activating tubuloglomerular feedback from enhanced distal sodium delivery. Osmotic nephropathy due to use of Canagliflozin has not been reported.
Case Description
A sixty eight year old diabetic, hypertensive Caucasian male, recovering from left septic knee due to group B streptococcus infection at a swing bed, got admitted with oliguric renal failure. His baseline creatinine was 1.2 mg/dL, with eGFR 62 ml.min and no baseline proteinuria, last A1c of 7.2% one month prior. One week prior to admission, he was started on Canagliflozin 300 mg daily. No history of volume depletion, and no evidence of hypotension, contrast exposure, or NSAID use noted. He was on furosemide 80 mg daily, Enalapril 5 mg daily. Complements were normal, urine revealed active sediment and 2.3 grams proteinuria. Hemodialysis was initiated due to oliguric AKI. Canagliflozin was stopped. Week after admission, creatinine improved to 1.7 mg/dL and the patient is off dialysis.Biopsy revealed features of osmotic nephrosis (Fig. 1).
Discussion
Enhanced glucose delivery to S3 segment of proximal tubule (PT) due to it's blocked uptake at S1 segment of PT by SGLT2-i, activates osmosensitive aldose reductase. Glucose is converted to sorbitol and to fructose. Fructose-uric acid axis is postulated in pathogenesis of chronic kidney injury related to diabetic nephropathy. In our case, although the exact etiology of osmotic nephrosis is not known, we hypothesize that higher concentrations of intracellular fructose may have caused local toxicity leading to the described pathological changes and severe acute renal failure.
Osmotic Nephrosis : Proximal tubule cell with severe vacuolization, loss of brush border, and cell death