Decongestion and Kidney Function Declines
- An acute decline in eGFR is not associated with higher risk of death or a composite outcome of CV death and hospitalization for HF as long as there is evidence of decongestion, either by declines in BNP, NT-proBNP, or weight or by increases in hematocrit, albumin, or total protein.
- However, if acute declines in eGFR are observed without evidence of concomitant decongestion, the declines in kidney function are associated with worse survival and increased risk of CV death and HF hospitalization.
Does incorporation of a comprehensive set of measures of decongestion modify the association of acute declines in kidney function with outcomes?
The study authors used data from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) trial, and multivariable Cox regression models to evaluate the association between in-hospital changes in estimated glomerular filtration rate (eGFR) with mortality and a composite outcome of cardiovascular (CV) death and hospitalization for heart failure (HF). They 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.
There were 3,715 patients with both baseline and follow-up kidney function data available. Median (25th, 75th interquartile range) follow-up was 9.9 (5.3, 16.1) months. In this study cohort over a median follow-up of 9.9 months, every 30% decline in eGFR was associated with higher risk of both mortality (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.31) and the composite outcome of CV death and hospitalization for HF (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; 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. When the relation between decline in eGFR and outcomes was examined within the context of changes in sodium and chloride, there was no significant interaction in fully adjusted models limited to the placebo arm. For the outcome of death, there was no significant interaction (p interaction = 0.35 and 0.76 for sodium and chloride, respectively). Similarly, there was no significant interaction for the composite outcome.
The authors concluded that 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 article supports what many HF physicians have known, that achieving dry weight is desirable despite earlier studies suggesting that azotemia is associated with poor prognosis. The findings of this study also suggest that if acute declines in eGFR are observed without evidence of concomitant decongestion, the declines in kidney function are associated with worse survival and increased risk of CV death and HF hospitalization. Prospective studies are now needed to confirm the important findings of this study.
Keywords: Azotemia, Biological Markers, Geriatrics, Glomerular Filtration Rate, Heart Failure, Hematocrit, Kidney Diseases, Natriuretic Peptide, Brain, Peptide Fragments, Renal Insufficiency, Secondary Prevention, Sodium
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