Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Lower eGFR Decline in Nondiabetic CKD Patients without Proteinuria

Key Points Sodium-glucose cotransporter 2 inhibitors (SGLT2is) significantly slowed chronic decline in eGFR in nondiabetic CKD patients without proteinuria. Propensity score–matched analysis confirmed that SGLT2i users had a significantly slower postinitial dip eGFR slope than nonusers. Subgroup analyses consistently supported the renoprotective effect of SGLT2is in this population. Background Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown promise as renoprotective agents, building on the success of renin-angiotensin system blockers. Although SGLT2is have been shown to slow renal deterioration in diabetic and nondiabetic CKD with proteinuria, it is unclear whether similar effects occur in nondiabetic, nonproteinuric CKD. Methods This study used propensity score analysis to evaluate the effects of SGLT2is on changes in annual eGFR in nondiabetic CKD patients with trivial proteinuria (urinary protein–creatinine ratio <0.5 g/gCr) who were seen at the Nara Prefecture General Medical Center from January 1, 2019, to December 31, 2022. The study analyzed 362 nondiabetic patients with CKD, including 211 SGLT2i users and 151 nonusers, with a median age of 65 (53–73) years, median eGFR of 45 (35–53) ml/min per 1.73 m 2 , and median urinary protein–creatinine ratio of 0.15 (0.09–0.29) g/gCr. Results Adjusted linear mixed-effects models showed that while the eGFR decline over a 3-year period (total) was similar between the two groups, there was a significantly smaller decline between 3 months after baseline and 2-year follow-up (chronic) in SGLT2i users compared with nonusers, with a difference of 1.23 (95% confidence interval, 0.43 to 2.02; P = 0.002) ml/min per 1.73 m 2 per year. After propensity score matching, SGLT2i users exhibited significantly slower chronic decline than nonusers, with a difference of 1.50 (95% confidence interval, 0.63 to 2.36; P < 0.001) ml/min per 1.73 m 2 per year. Subgroup analyses confirmed these findings. Conclusions This study suggests that SGLT2is may slow eGFR decline in non-diabetic CKD patients with trivial proteinuria, supporting the potential use of SGLT2is as renoprotective agents in this population.