AbstractAimsAcute heart failure (HF) is associated with muscle mass loss, potentially leading to overestimation of kidney function using serum creatinine‐based estimated glomerular filtration rate (eGFR_sCr). Cystatin C‐based eGFR (eGFR_CysC) is less muscle mass dependent. Changes in the difference between eGFR_CysC and eGFR_sCr may reflect muscle mass loss. We investigated the difference between eGFR_CysC and eGFR_sCr and its association with clinical outcomes in acute HF patients.Methods and resultsA post hoc analysis was performed in 841 patients enrolled in three trials: Diuretic Optimization Strategy Evaluation (DOSE), Renal Optimization Strategies Evaluation (ROSE), and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS‐HF). Intra‐individual differences between eGFRs (eGFR_diff) were calculated as eGFR_CysC–eGFR_sCr at serial time points during HF admission. We investigated associations of (i) change in eGFR_diff between baseline and day 3 or 4 with readmission‐free survival up to day 60; (ii) index hospitalization length of stay (LOS) and readmission with eGFR_diff at day 60. eGFR_CysC reclassified 40% of samples to more advanced kidney dysfunction. Median eGFR_diff was −4 [−11 to 1.5] mL/min/1.73 m² at baseline, became more negative during admission and remained significantly different at day 60. The change in eGFR_diff between baseline and day 3 or 4 was associated with readmission‐free survival (adjusted hazard ratio per standard deviation decrease in eGFR_diff: 1.14, P = 0.035). Longer index hospitalization LOS and readmission were associated with more negative eGFR_diff at day 60 (both P ≤ 0.026 in adjusted models).ConclusionsIn acute HF, a marked difference between eGFR_CysC and eGFR_sCr is present at baseline, becomes more pronounced during hospitalization, and is sustained at 60 day follow‐up. The change in eGFR_diff during HF admission and eGFR_diff at day 60 are associated with clinical outcomes.