Early Relative eGFR Decline After SGLT2 Inhibitor Initiation in Heart Failure: Clinical Correlates and Pretreatment-Anchored 12-Month Trajectories

Background/Objectives: Early changes in estimated glomerular filtration rate (eGFR) after sodium–glucose cotransporter 2 (SGLT2) inhibitor initiation in heart failure (HF) are difficult to interpret in routine practice. We assessed the clinical correlates of >10% early relative eGFR decline and the subsequent trajectories relative to the pretreatment eGFR. Methods: This retrospective single-center study included 295 patients with HF who remained on SGLT2 inhibitor treatment at their first eligible creatinine assessment on days 10–45 (median 25 days [IQR 21–30]; range 10–42). Multivariable regression, mixed-effects modeling, and within-patient paired analyses were used. Results: Among the 333 initiation episodes, 33 (9.9%) were excluded after early treatment discontinuation, and five repeat episodes were removed. Early decline >10% occurred in 110/295 patients (37.3%). Age ≥ 80 years (adjusted OR 2.14, 95% CI 1.21–3.81), female sex (2.51, 1.42–4.44), higher baseline eGFR per 10 mL/min/1.73 m2 (1.43, 1.21–1.69), and loop-diuretic use (1.82, 1.03–3.23) were associated with decline; the loop-diuretic association attenuated in an expanded model. Twelve-month eGFR was available for 195/295 patients (66.1%). Among the 71 with >10% early decline and paired 12-month data, the mean eGFR increased by 4.70 mL/min/1.73 m2 from the early assessment but remained 6.99 mL/min/1.73 m2 below the pretreatment (both p < 0.001). Conclusions: In this selected cohort, a mean increase after early decline did not indicate a return to the pretreatment mean. The interpretation of an isolated early eGFR value requires clinical context and subsequent measurements.