Acute Declines in Kidney Function in the Context of Decongestion in Patients with Acute Decompensated Heart Failure

Background: In-hospital acute declines in kidney function occur in approximately 20–30% of patients admitted with acute decompensated heart failure (ADHF) and may be associated with adverse outcomes. Objective: To examine whether incorporation of a comprehensive set of measures of decongestion modifies the association of acute declines with outcomes. Methods: Using data from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial, we used multivariable Cox regression models to evaluate the association between in-hospital changes in estimated glomerular filtration rate (eGFR) with death and a composite outcome of cardiovascular death and heart failure hospitalization. We evaluated eGFR declines within the context of changes in markers of volume overload including b-type natriuretic peptide (BNP), N-terminal prohormone of b-type natriuretic peptide (NT-proBNP), and weight, as well as changes in measures of hemoconcentration including hematocrit, albumin and total protein. Results: Among 3,715 patients over a median follow-up of 9.9 months, every 30% decline in eGFR was associated with higher risk of both death (HR=1.19 [95% CI 1.07, 1.31] and the composite outcome (HR=1.09 [95% CI 1.01, 1.18]) in adjusted models. The acute decline in eGFR was no longer associated with higher risk of either outcome as long as there was evidence of decongestion, either by declines in BNP, NT-proBNP or weight or by increases in hematocrit, albumin or total protein. Interaction testing between decline in eGFR and changes in hematocrit, albumin and total protein was statistically significant (p-interaction of <0.01 for death and p-interaction of ≤0.01 for composite for all three biomarkers). Interaction between change in eGFR and changes in BNP (p-interaction=0.07 for death; 0.08 for composite), NT-proBNP (p-interaction=0.15 for death; 0.18 for composite) and weight (p-interaction=0.13 for death; 0.19 for composite) did not meet statistical significance. Conclusion: Overall, acute declines in eGFR are associated with adverse outcomes, with evidence of modification by changes in markers of decongestion, suggesting that they are no longer associated with adverse outcomes if these markers are concomitantly improving. Condensed Abstract Among 3,715 patients from the EVEREST trial, we observed that the relation between acute declines in estimated glomerular filtration rate (eGFR) and outcomes was modified by changes in markers of volume overload (b-type natriuretic peptide, N-terminal prohormone of b-type natriuretic peptide, weight) and markers of hemoconcentration (hematocrit, albumin, total protein). Among those with the least improvement in markers of volume overload or hemoconcentration, acute eGFR declines were associated with higher risk of death and cardiovascular events. However, among those displaying greater improvement in volume overload and hemoconcentration, there was no association between eGFR decline and risk of adverse outcomes. Cox proportional hazards regression models were used to evaluate the interaction between decline in eGFR and change in surrogate measures of volume overload (BNP, NT-proBNP and weight) by change in surrogate measures of hemoconcentration (hematocrit, albumin and total protein). greatest increase. Interaction testing was performed with decline in eGFR and change in biomarkers both on the continuous scale (represented as p-interaction).