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SGLT2 Inhibitor-Associated Changes in Urinary Volatile Organic Compounds in Diabetic Kidney Disease: A Comprehensive

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Sodium-glucose cotransporter-2 (SGLT2) inhibitors increase urinary ketone bodies in diabetic kidney disease (DKD) patients. This non-invasive urinary metabolite profiling reveals metabolic shifts, aiding understanding of SGLT2 inhibitors

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Area of Science:

  • Metabolomics
  • Nephrology
  • Endocrinology

Background:

  • Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially for type 2 diabetes, show kidney-protective effects in diabetic kidney disease (DKD).
  • The metabolic mechanisms behind SGLT2 inhibitors' renoprotective actions in DKD are not fully understood.

Purpose of the Study:

  • To investigate the metabolic mechanisms of SGLT2 inhibitors in DKD using non-invasive urinary metabolite profiling.
  • To identify urinary volatile organic compounds (VOCs) associated with SGLT2 inhibitor treatment in DKD patients.

Main Methods:

  • Gas chromatography-mass spectrometry was used to analyze urinary VOCs in 61 DKD patients.
  • Patients were categorized into SGLT2 inhibitor-treated and untreated groups.
  • 79 urinary VOCs were identified and quantified; clinical variables were statistically analyzed.

Main Results:

  • SGLT2 inhibitor-treated patients exhibited significantly higher urinary levels of acetone and 2-pentanone.
  • These elevated VOCs, derived from ketone bodies, suggest increased ketogenesis.
  • Findings were consistent across patients and independent of other clinical characteristics.

Conclusions:

  • SGLT2 inhibitor therapy is linked to increased urinary ketone-related VOCs, indicating a metabolic shift towards altered systemic energy metabolism.
  • Urinary VOC profiling offers a promising non-invasive method for understanding SGLT2 inhibitor mechanisms and monitoring treatment effects in DKD.
  • This study provides novel mechanistic insights into the kidney protection offered by SGLT2 inhibitors.