Association of the Timing of Acute Declines in Kidney Function in Acute Heart Failure With Cardiovascular and Kidney Outcomes

RATIONALE & OBJECTIVE: Inconsistencies in the association of acute declines in kidney function with longer-term cardiovascular (CV) and kidney outcomes in patients with acute heart failure (AHF) may be due to different approaches to assessing the timing of the decline. This study examined the influence of the timing of acute kidney function decline among patients with AHF on the associations of these declines with mortality, CV outcomes, and long-term kidney function. STUDY DESIGN: Observational analysis of clinical trial data. SETTING & PARTICIPANTS: Participants in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial hospitalized for AHF. EXPOSURE: Kidney function decline (defined by creatinine increase by ≥0.3 mg/dL, creatinine increase by >50%, and percentage of creatinine change) at 3 different time points (3, 7, and 14 days after randomization). OUTCOME: Mortality, a composite of CV mortality or heart failure (HF) hospitalization, incident estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m ANALYTICAL APPROACH: Analytical Approach: Multivariable cause-specific proportional hazards regression models. RESULTS: Among 3,931 patients over a median follow-up of 9.9 months, acute kidney function decline at 3 days was not associated with mortality (HR, 0.98 95% CI, 0.88-1.09 per 30% creatinine increase) or with the composite outcome of CV mortality and HF hospitalization (HR, 0.96 95% CI, 0.89-1.05). By contrast, acute kidney function decline at 7 days after randomization was associated with a higher risk of mortality (HR, 1.19 95% CI, 1.10-1.30 per 30% creatinine increase) and the composite outcome (HR, 1.10 95% CI, 1.03-1.18). Acute kidney function decline at 14 days after randomization also was associated with a higher risk of mortality (HR, 1.27 95% CI, 1.16-1.38 per 30% creatinine increase) and the composite outcome (HR, 1.15 95% CI, 1.08-1.23). Acute kidney function declines at 3, 7, and 14 days after randomization were all associated with significantly higher risk of incident eGFR < 30 mL/min/1.73 m LIMITATIONS: Limited generalizability from the study of clinical trial participants. CONCLUSIONS: Among patients hospitalized for AHF, incorporating the timing of acute kidney function declines may inform prognostic assessment of CV end points. Acute declines in kidney function at all studied time points were associated with longer-term kidney function. PLAIN-LANGUAGE SUMMARY: Acute declines in kidney function are frequently encountered among patients admitted for acute heart failure. Using data from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial, we evaluated whether the timing of an acute decline in kidney function may inform the relationship of those declines with the risk of death and other adverse cardiovascular outcomes. We found that early declines in kidney function 3 days after randomization were not associated with death or cardiovascular outcomes. However, declines occurring at 14 days and as early as 7 days were associated with higher risks. Declines at any of these times were associated with worse kidney function over time.