Large Early eGFR Decline on SGLT2 Inhibitors Linked to Mortality in CKD

An early decline in estimated glomerular filtration rate (eGFR) of 20% or more after starting a sodium-glucose cotransporter 2 (SGLT2) inhibitor was associated with higher short-term all-cause mortality among hospitalized patients with chronic kidney disease (CKD), according to a multicenter retrospective cohort study published in the Clinical Kidney Journal.

The authors noted that SGLT2 inhibitors are recommended as first-line therapy for CKD and that small, early declines in kidney function are expected. The implications of larger declines for patient outcomes remain unclear.

Investigators used the China Renal Data System to study 1,258 hospitalized adults with CKD and a baseline eGFR of at least 20mL/min/1.73m² who newly initiated an SGLT2i. Overall, 22.5% had an eGFR decline of 20% or more within 14 to 30 days. Within the first 45 days of follow-up, mortality was 5.2 per 100 person-months in this group vs 0.6 per 100 person-months among patients with smaller declines. After adjustment, a decline of 20% or more was associated with higher 45-day mortality (adjusted hazard ratio, 8.08; 95% CI, 3.41-19.13). Among patients who survived beyond 45 days, the analysis did not find a clear association with mortality from day 46 to 1 year (adjusted hazard ratio, 0.91; 95% CI, 0.48-1.74).

Large declines were more common in patients older than 60 years and in those with heart failure, diuretic use, or CKD stages 2 to 4. Results were consistent in sensitivity analyses and with alternative thresholds of 10% and 30%. The authors cautioned that the limited number of events produced wide confidence intervals.

Because the study was observational, residual confounding cannot be excluded, and the authors noted that the higher mortality may reflect, at least in part, underlying disease severity or clinical vulnerability rather than a direct effect of the decline itself. Other limitations included relatively short follow-up and possible selection bias that could overestimate the association. The authors concluded that, for patients with a substantial decline, they should be reassessed for potentially reversible causes before therapy is automatically stopped, while noting that treatment continuation decisions were beyond the study’s scope.

Source: Gao Q, Ma Z, Ren W, et al. Substantial declines in eGFR after initiation of SGLT2-inhibitors associate with increased short-term mortality in hospitalized patients with CKD. Clin Kidney J. Published online October 29, 2026. Doi 10.1093/ckj/sfag386