Substantial Declines in eGFR After Initiation of SGLT2-Inhibitors Associate with Increased Short-term Mortality in Hospitalized Patients With CKD

Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are recommended as first-line therapy for patients with chronic kidney disease (CKD). However, the prevalence and prognostic significance of a large early eGFR dip after SGLT2i initiation in real-world CKD populations remain unclear. Methods We conducted a multicenter retrospective cohort study using the China Renal Data System. Adult hospitalized patients with estimated glomerular filtration rate (eGFR) ≥20 ml/min/1.73m2 who newly initiated SGLT2i were included. Exposure was defined as an eGFR decline ≥ 20% within 14–30 days after treatment initiation. Follow-up began 30 days after initiation. The outcomes were all-cause mortality within 45 days and all-cause mortality from 46 days to 1 year. Inverse probability of treatment weighting (IPTW)-weighted landmark Cox model was performed to evaluate these associations. Results Among 1 258 eligible patients (mean age 64.4 years; 69.3% male), 22.5% experienced an early eGFR dip ≥ 20%. Higher incidence rates were observed in older patients, those with heart failure, diuretic use, and CKD stages 2–4. Compared with an eGFR dip < 20%, an eGFR dip ≥ 20% was associated with an increased risk of all-cause mortality within 45 days (adjusted hazard ratio [aHR], 8.08; 95% confidence interval [CI], 3.41–19.13). However, no significant association was observed between an eGFR dip ≥ 20% and all-cause mortality from 46 days to 1 year (aHR, 0.91; 95% CI, 0.48–1.74). Conclusions A substantial eGFR decline after SGLT2i initiation was not uncommon and was associated with increased short-term all-cause mortality, highlighting the importance of close kidney function monitoring and individualized clinical assessment of treatment continuation.