Results:

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.