Identification of risk factors associated with acute kidney injury in patients taking sodium-glucose cotransporter-2 inhibitors

Pharmacotherapy. 2024 Mar;44(3):249-257. doi: 10.1002/phar.2902. Epub 2024 Jan 12.

Abstract

Study objective: Studies have demonstrated sodium-glucose cotransporter-2 (SGLT2) inhibitors are kidney protective; however, their ability to cause hemodynamic changes may predispose patients to acute kidney injury (AKI). An FDA warning recommends evaluating for factors that predispose patients to AKI before initiating a SGLT2 inhibitor. The primary objective of this study is to identify risk factors that may predispose persons with diabetes to AKI when initiating SGLT2 inhibitor therapy.

Design: Multicenter retrospective cohort chart review.

Data source: Study patients were identified through an electronic medical record generated report if they had type 2 diabetes and were prescribed a SGLT2 inhibitor from January 2013 to September 2019.

Patients: Patients were included if they were receiving care at Advocate Medical Group and were confirmed to have taken one of the four SGLT2 inhibitors available at the time of study approval, canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin, for at least 7 days. Patients were excluded if they did not have a basic metabolic panel or comprehensive metabolic panel recorded 1 year prior to or 6 months after SGLT2 inhibitor therapy initiation.

Results: Data extraction from the electronic medical record identified 6425 patients receiving a SGLT2 inhibitor, of which 1962 met inclusion criteria and were included for analysis. Thirty-five (1.8%) patients experienced an AKI after SGLT2 inhibitor therapy initiation. There was no statistically significant difference between groups based on background medication use (p = 0.325). At baseline, patients experiencing an AKI after SGLT2 inhibitor initiation were more likely to be older in age (p = 0.010), have a higher serum potassium (p < 0.001), blood glucose (p = 0.018), SCr (p = 0.009) and UACR (p < 0.001), and a lower eGFR (p = 0.028) compared to those who did not experience AKI.

Conclusions: The transient eGFR decline with SGLT2 inhibitor initiation should be expected and is generally not an indication to discontinue therapy. Future initiatives should be directed at increasing knowledge of monitoring recommendations for these agents.

Keywords: acute kidney injury; adverse drug reactions; diabetes; sodium-glucose transporter 2 inhibitors.

Publication types

  • Multicenter Study

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / epidemiology
  • Blood Glucose
  • Diabetes Mellitus, Type 2*
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Retrospective Studies
  • Risk Factors
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Blood Glucose
  • Sodium
  • Hypoglycemic Agents