Substantial Declines in eGFR After Initiation of SGLT2-Inhibitors Associate with Increased Short-term Mortality in Hospitalized Patients With CKD
Qi Gao, Zhou Ma, Weirong Ren, Yaping Yu, Lunlun Wu, Zhiqin Zhang, Zhongcai Wu, Shiyu Zhou, Licong Su, Yanqin Li, Fan Luo, Yuxin Lin, Junwu Dong, Honglan WeiAbstract
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.