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

Abstract

Objectives: This study aimed to examine whether incorporation of a comprehensive set of measures of decongestion modifies the association of acute declines in kidney function with outcomes.

Background: In-hospital acute declines in kidney function occur in approximately 20% to 30% of patients admitted with acute decompensated heart failure (ADHF) and may be associated with adverse outcomes.

Methods: Using data from EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan), 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 hospitalization for heart failure. 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 (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.07 to 1.31) and the composite outcome (HR: 1.09; 95% CI: 1.01 to 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 3 biomarkers). Interaction between change in eGFR and changes in BNP (p interaction = 0.07 for death; p interaction = 0.08 for composite), NT-proBNP (p interaction = 0.15 for death; p interaction = 0.18 for composite) and weight (p interaction = 0.13 for death; p interaction = 0.19 for composite) did not meet statistical significance.

Conclusions: 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.

Keywords: cardiorenal; decongestion; hemoconcentration; worsening renal function.

Figure 1.

Adjusted hazards ratios for death per every 30% decline in eGFR according to varying levels of change in biomarkers of volume overload (a) and biomarkers of hemoconcentration (b). 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) and by change in surrogate measures of hemoconcentration (hematocrit, albumin and total protein). Abbreviations: BNP, b-type natriuretic peptide; eGFR, estimated glomerular filtration rate; NT-proBNP: N-terminal prohormone of b-type natriuretic peptide

Figure 2.

Adjusted hazard ratios for death per every 30% eGFR decline within quartiles of change in biomarkers of volume overload (a) and biomarkers of hemoconcentration (b). Cox proportional hazards regression models examining decline in eGFR within quartiles of change in measures of volume overload (BNP, NT-proBNP and weight) with quartile 1 representing the least decrease and quartile 4 representing the greatest decrease; and within quartiles of change in measures of hemoconcentration (hematocrit, albumin and total protein) with quartile 1 representing the least increase and quartile 4 representing the greatest increase. Interaction testing was performed with decline in eGFR and change in biomarkers both on the continuous scale (represented as p-interaction). Abbreviations: BNP,b-type natriuretic peptide; eGFR, estimated glomerular filtration rate; NT-proBNP: N-terminal prohormone of b-type natriuretic peptide

Central Illustration.

The acute decline in estimate glomerular filtration rate (eGFR) is associated with higher risk of death over a median 10-month follow-up. On the other hand, decongestion as measured by decline in b-type natriuretic peptide (BNP) and hemoconcentration as measured by increase in hematocrit, are associated with decreased risk of death. The association between decline in kidney function and death is modified by the change in these biomarkers of decongestion and hemoconcentration. That is, acute declines in kidney function are only associated with increased risk for death and cardiovascular outcomes when markers of decongestion worsened, but not when they improved.