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

Wendy McCallum, MD, MS; Hocine Tighiouart, MS; Jeffrey M. Testani, MD, MTR; Matthew Griffin, MD; Marvin A. Konstam, MD; James E. Udelson, MD; Mark J. Sarnak, MD, MS

Disclosures

JACC Heart Fail. 2020;8(7):537-547. 

In This Article

Abstract and Introduction

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.

Introduction

Approximately 20% to 30% of patients admitted for acute decompensated heart failure (ADHF) experience a decline in kidney function during their hospitalization.[1,2] The pathophysiology of this decline is not well understood, and its association with post-discharge outcomes is controversial. Many mechanisms have been proposed to explain declines in kidney function among patients with ADHF, including renal congestion from volume overload.[3,4] Improvements in kidney function have been observed following fluid removal;[5] however, fluid removal can also lead to acute declines in estimated glomerular filtration rate (eGFR).[6,7]

Acute declines in eGFR pose a dilemma for clinicians, who may feel tempted to discontinue decongestion prematurely out of concern for the kidney function, given the association of baseline reduced kidney function with adverse outcomes. Previous post hoc analyses have suggested that, as long as occurring within the setting of decongestion, acute declines in kidney function may be tolerated.[8,9] Many of these studies have relied on rise in a single biomarker of hemoconcentration, such as hematocrit, but increases in hematocrit have not always been associated with degree of fluid removal. Natriuretic peptides, which are released in response to cardiac stretch in states of volume overload, can also serve as surrogates of congestion. A previous analysis has also shown that declines in kidney function may be associated with improved clinical outcomes if occurring in the context of decreases in N-terminal prohormone of B-type natriuretic peptide (NT-proBNP).[10]

Using data from EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan), we sought to investigate the relation between acute declines in kidney function with mortality and cardiovascular outcomes, as well as between changes in markers of decongestion with these clinical outcomes. Our primary goal was to evaluate and compare a comprehensive set of markers of volume overload, including changes in B-type natriuretic peptide (BNP), its prohormone NT-proBNP, and weight—as well as markers of hemoconcentration including changes in hematocrit, albumin, and total protein—to evaluate whether they can better inform clinicians in interpreting acute declines in kidney function.

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