A randomised controlled study of canagliflozin in improving diabetic kidney disease through a podocyte protection...

This study aimed to investigate whether canagliflozin improves diabetic kidney disease (DKD) through a podocyte protective mechanism.

DKD patients were randomly assigned to the experimental group (87 patients: standard therapy plus cangliflozin 100 mg/day) and the control group (85 patients: standard therapy plus placebo tablets), with a treatment course of 12 weeks. Investigators and outcome assessors were blinded to allocation. Changes in blood glucose, DKD-related indicators (serum albumin, serum creatinine, blood urea nitrogen [BUN], 24-hour urinary protein [24h-UP], urinary albumin-to-creatinine ratio (UACR), and podocyte injury markers (urinary podocyte count, urinary podocalyxin-to-urinary creatinine ratio [UPCX/Ucr]) were compared. Linear mixed-effects models were used to compare intergroup differences, and mediation effect analysis was performed to evaluate the role of UPCX/Ucr in the improvement of DKD-related indicators by canagliflozin.

Under comparable blood glucose control, the experimental group showed superior outcomes in reducing BUN (between‑group difference at week 12: -0.67 mmol/L, 95% confidence interval [CI] -1.10 to -0.24), 24h-UP (geometric mean ratio 0.73, 95% CI 0.65 to 0.82), UACR (geometric mean ratio 0.72, 95% CI 0.65 to 0.80), urinary podocyte count (geometric mean ratio 0.48, 95% CI 0.43 to 0.54), and UPCX/Ucr (geometric mean ratio 0.72, 95% CI 0.66 to 0.79) compared to the control group. Mediation analysis revealed that UPCX/ Ucr exerted a significant indirect effect in the reduction of UACR (indirect effect = -0.968, 95% CI -1.171 to -0.774) and 24h‑UP (indirect effect = -0.783, 95% CI -1.127 to -0.655) by canagliflozin, with no statistically significant direct effects. For serum creatinine reduction, UPCX/Ucr played a partial mediating role with a small indirect effect (indirect effect = -0.301, 95% CI -0.437 to -0.153), alongside a significant direct effect.

Canagliflozin provides significant renal protective effects for DKD patients, effectively lowering blood glucose while reducing urinary protein, lowering serum creatinine from baseline, and protecting podocytes. The reduction in urinary protein appears to be statistically mediated by podocyte protection, rather than being solely dependent on blood glucose control. However, this mediation analysis does not establish causality.