Urinary Glucose Concentration as a Predictor of Proteinuria Reduction in Chronic Kidney Disease Patients Treated with Sodium-Glucose Cotransporter 2 Inhibitors.

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are crucial in managing proteinuria in chronic kidney disease (CKD), yet individual responses vary. Whether urinary glucose excretion, a direct pharmacodynamic marker of SGLT2is, could predict proteinuria reduction efficacy remains unclear and has not been specifically investigated. METHODS: We enrolled 277 CKD patients treated with empagliflozin (10 mg/day) between July 2024 and September 2025 at a single center, stratifying them into low (<46.4 mmol/L, n = 69) and high (≥46.4 mmol/L, n = 208) urinary glucose groups by 24-h urinary glucose levels after 3 months of treatment. We evaluated changes in proteinuria levels following 3 and 6 months of medication across the different urinary glucose groups. Changes in laboratory values over time were analyzed using paired Wilcoxon signed-rank tests. RESULTS: Proteinuria was significantly reduced at both 3 (-0.42 g/24 h [95% confidence interval [CI]: -0.55 to -0.32]) and 6 months (-0.46 g/24 h [95% CI: -0.61 to -0.33]) after treatment initiation. After adjusting for covariates, urinary glucose excretion predicted proteinuria reduction from 3 to 6 months (β = 2.47, 95% CI: 0.49-4.45, p = 0.015), with higher urinary glucose correlating with greater proteinuria decline. The high urinary glucose group had significant proteinuria reduction from baseline at 3 and 6 months (p < 0.001), unlike the low group. Following propensity score adjustment for age, sex, body mass index, baseline estimated glomerular filtration rate (eGFR), and renin-angiotensin-aldosterone system inhibitors use, the high urinary glucose group had a significantly higher relative risk of ≥30% proteinuria reduction (risk ratio = 2.82, 95% CI: 1.20-6.65, p = 0.017), particularly in patients with baseline proteinuria ≥1 g/24 h. Urinary glucose concentration was weakly positively correlated with 6-month eGFR change (r = 0.17, p = 0.011). CONCLUSIONS: Urinary glucose concentration can serve as a predictor of SGLT2i-mediated proteinuria reduction, providing a practical clinical reference for personalized CKD management.