Effects of SGLT2 Inhibitors on Lower eGFR Decline in Non-Diabetic CKD Patients without Proteinuria.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown promise as renoprotective agents, building on the success of renin-angiotensin system blockers. While SGLT2i have been shown to slow renal deterioration in diabetic and non-diabetic chronic kidney disease (CKD) with proteinuria, it is unclear if similar effects occur in non-diabetic, non-proteinuric CKD.

Methods: This study used propensity-score analysis to evaluate the effects of SGLT2i on changes in the annual estimated glomerular filtration rate (eGFR) in non-diabetic CKD patients with trivial proteinuria (urinary protein-creatinine ratio (UPCR) < 0.5 g/gCr) who were seen at Nara Prefecture General Medical Center from January 1, 2019, to December 31, 2022. The study analyzed 362 non-diabetic CKD patients, including 211 SGLT2i users and 151 non-users, with a median age of 65 (53-73) years, a median eGFR of 45 (35-53) mL/min/1.73m2, and a median UPCR 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) were 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 non-users, with a difference of 1.23 (95% confidence interval (CI): 0.43-2.02, p=0.002) mL/min/1.73m2/year. After propensity-score matching, SGLT2i users exhibited significantly slower chronic decline than non-users, with a difference of 1.50 (95%CI: 0.63-2.36, p<0.001) mL/min/1.73m2/year. Subgroup analyses confirmed these findings.

Conclusions: This study suggests that SGLT2i may slow eGFR decline in non-diabetic CKD patients with trivial proteinuria, supporting the potential use of SGLT2i as renoprotective agents in this population.