Author + information
- Received January 15, 2020
- Revision received March 5, 2020
- Accepted March 5, 2020
- Published online June 29, 2020.
- Wendy McCallum, MD, MSa,
- Hocine Tighiouart, MSb,
- Jeffrey M. Testani, MD, MTRc,
- Matthew Griffin, MDc,
- Marvin A. Konstam, MDd,
- James E. Udelson, MDd and
- Mark J. Sarnak, MD, MSa,∗ ()
- aDivision of Nephrology, Tufts Medical Center, Boston, Massachusetts
- bInstitute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts Clinical and Translational Science Institute, Tufts University, Boston, Massachusetts
- cDivision of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut
- dDivision of Cardiology and the CardioVascular Center, Tufts Medical Center, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Mark J. Sarnak, Box 391, Division of Nephrology, Tufts Medical Center, 800 Washington Street, Boston, Massachusetts 02111.
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.
This manuscript was funded by National Institutes of Health training grant T32 DK007777. Dr. Testani has received grant support from Otsuka and Abbott; has received grants and consulting fees from Bristol-Myers Squibb (BMS), 3ive Labs, Boehringer Ingelheim, MagentaMed, Sanofi, and FIRE1; has receivedconsulting fees from AstraZeneca, Novartis, Cardionomic, Bayer, Reprieve Medical, and W.L. Gore. Dr. Udelson received research support from Otsuka. Dr. Konstam received research support from Otsuka and SC Pharma; and serves as a Data Safety and Monitoring Board chair for Bristol-Myers Squibb. Dr. Sarnak serves on the steering committee for Akebia; attended Advisory Board Meetings for Bayer; and has received consulting fees from Cardurian. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Heart Failure author instructions page.
- Received January 15, 2020.
- Revision received March 5, 2020.
- Accepted March 5, 2020.
- 2020 American College of Cardiology Foundation
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