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Case Reports
. 2020 Jul;76(1):144-147.
doi: 10.1053/j.ajkd.2020.01.015. Epub 2020 May 5.

Osmotic Nephrosis and Acute Kidney Injury Associated With SGLT2 Inhibitor Use: A Case Report

Gautam Phadke  1 , Amit Kaushal  1 , Dean R Tolan  2 , Kai Hahn  3 , Thomas Jensen  4 , Petter Bjornstad  4 , Carlos Roncal-Jimenez  4 , Ana Andres Hernando  4 , Miguel A Lanaspa  4 , Mariam Priya Alexander  5 , Aleksandra Kukla  6 , Richard J Johnson  7
Affiliations
Case Reports

Osmotic Nephrosis and Acute Kidney Injury Associated With SGLT2 Inhibitor Use: A Case Report

Gautam Phadke et al. Am J Kidney Dis. 2020 Jul.

Abstract

We report a case of a patient who developed dialysis-requiring acute kidney injury (AKI) after the use of canagliflozin. A 66-year-old man with type 2 diabetes who was recovering from left knee septic arthritis at a rehabilitation facility was admitted with oliguric AKI 5 days after starting treatment with canagliflozin, an inhibitor of sodium/glucose cotransporter 2 (SGLT2). The patient presented with hematuria, non-nephrotic-range proteinuria, and serum creatinine level of 6.8 (baseline, 1.1-1.3) mg/dL. There was no recent use of radiocontrast agents or exposure to other nephrotoxins. The patient subsequently required hemodialysis. Due to recent antibiotic use (ampicillin-sulbactam), acute interstitial nephritis was considered in the differential diagnosis. Kidney biopsy was performed, which showed the presence of osmotic nephropathy. The patient's kidney function returned to baseline after 2 weeks of hemodialysis. This case provides evidence of an association of osmotic nephropathy with the use of canagliflozin and discusses potential mechanisms. We recommend kidney biopsy for cases of severe AKI associated with SGLT2 inhibitors to better understand the relationship of this complication with the use of this class of medications.

Keywords: Acute renal failure (ARF); SGLT2 inhibitors; acute kidney injury (AKI); canagliflozin; case report; hemodialysis; kidney biopsy; osmotic nephropathy; sodium/glucose cotransporter 2 (SGLT2).

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Conflict of interest statement

Authors with Conflict of Interest:

  1. Peter Bjornstad: PB has acted as a consultant for Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Sanofi, Novo Nordisk and Horizon Pharma. PB serves on the advisory board of XORTX.

  2. Richard Johnson, Miguel Lanaspa and Carlos Roncal-Jimenez: have equity with Colorado Research Partners LLC that is making inhibitors of fructose metabolism.

  3. All the authors did NOT receive any funding toward the production of the manuscript.

Figures

Figure 1.
Figure 1.. Osmotic Nephrosis in a Patient with Canagliflozin-Mediated AKI.
A. PAS stain shows vacuolated cytoplasm of proximal tubular cells consistent with severe osmotic nephrosis (40x magnification). B. PAS stain at high power showing the presence of small glycogen deposition (pink dots, arrows) in the cytoplasm of the injured proximal tubular epithelium (100x). Documentation this was glycogen was shown by diastase staining. C. Oil Red O staining shows the presence of rare positive lipid deposits in some proximal tubules (arrows, 40x). D. Immunofluorescence of some proximal tubules for aldose reductase (white arrows 40x). E. As in D) but for fructokinase (white arrows, 100x).
See this image and copyright information in PMC

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