The Nigerian Postgraduate Medical Journal · Nov 2, 2026

Urinary Volatile Organic Compounds as Pharmacodynamic Biomarkers in Sodium-glucose Cotransporter 2 Inhibitor-treated Diabetic Kidney Disease

By Mathew GG, Ramanathan G

Sodium-glucose cotransporter 2 (SGLT2) inhibitors confer renoprotection in diabetic kidney disease (DKD) through haemodynamic, anti-inflammatory and metabolic mechanisms, including hepatic ketogenesis induction. A recent investigation by Hara et al . demonstrated measurable elevations in urinary volatile organic compounds (VOCs), specifically acetone and 2-pentanone, in SGLT2 inhibitor-treated DKD patients using gas chromatography-mass spectrometry, providing direct metabolomic evidence of pharmacodynamic ketogenic interaction. This review contextualises these findings within the mechanistic framework of SGLT2 inhibitor-mediated renoprotection, particularly ketone body-induced suppression of mammalian target of rapamycin complex 1 in proximal tubular cells. This manuscript proposes three clinically actionable roles for urinary VOC monitoring: as a pharmacodynamic biomarker of drug engagement, a longitudinal marker of renoprotective responsiveness and a non-invasive early warning signal for euglycemic diabetic ketoacidosis. A pragmatic four-step algorithmic framework is presented to guide clinicians in integrating urinary VOC profiling with established DKD monitoring parameters. The key limitations including analytical confounders, acetoacetate instability and the need for point-of-care technology development are discussed in this minireview. Urinary VOC metabolomics represents a promising frontier in precision nephrology and individualised SGLT2 inhibitor-mediated DKD management.

doi.org/10.4103/npmj.npmj_291_26PubMed 42975214Interventions