Development of osmotic vacuolization of proximal tubular epithelial cells following treatment with sodium-glucose transport protein 2 inhibitors in type II diabetes mellitus patients-3 case reports

CEN Case Rep. 2021 Nov;10(4):563-569. doi: 10.1007/s13730-021-00609-7. Epub 2021 May 22.

Abstract

We encountered 3 cases of acute kidney injury that occurred after treatment with a SGLT2 inhibitor. In case 1, serum creatinine increased from 1.65 to 3.0 mg/dL, in case 2, serum creatinine increased from 1.03 to 1.21 mg/dL, and in case 3, serum creatinine increased from 0.8 to 1.1 mg/dL. Renal biopsy showed isometric vacuolization on tubules, that was completely negative for Periodic acid-Schiff (PAS) stain in case 1, and was partially negative for PAS stain in case 2 and 3, consistent with osmotic vacuolization. Immunohistochemical analysis showed positive staining for CD138 and CD10 indicating the proximal tubules in the vacuolar lesions. 3 patients were obese with body mass index of more than 30, and showed an increase in serum renin. In conclusion, in type II diabetes mellitus (T2DM), individuals that remain within their standard weight range, SGLT2 inhibitor treatment does not result in osmotic vacuolization of proximal tubular epithelial cells and AKI. However, treatment with a SGLT2 inhibitor may cause damage of the proximal tubules resulting in AKI in T2DM individuals who do not remain within their standard weight range, due to an overdose lavage of sugar in the urine and dehydration.

Keywords: Acute kidney injury (AKI); Isometric vacuolization; Osmotic vacuolization; Proximal tubules; Sodium-glucose transport protein 2 (SGLT2); Type II diabetes mellitus (T2DM).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Humans
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / pathology
  • Kidney Tubules, Proximal / ultrastructure*
  • Male
  • Middle Aged
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects*
  • Vacuoles / ultrastructure

Substances

  • Sodium-Glucose Transporter 2 Inhibitors