Acute kidney injury (AKI) and heart failure exist in a bidirectional relationship that has yet to be fully realized. Recently, a Vanderbilt University Medical Center study found that AKI may be linked to the condition of heart failure with preserved ejection fraction (HFpEF).
Understanding the links between AKI and specific types of heart failure – either with preserved or reduced ejection fraction – could offer insights to improve post-AKI care, according to Evan Brittain, M.D., a professor of medicine in the Division of Cardiovascular Medicine at VUMC.
“Heart failure and kidney injury exist in a complex, two-way relationship, where dysfunction in one organ can lead to or stem from dysfunction in the other,” Brittain said. “As clinicians, we need to understand this relationship better.”
Brittain co-led the study, published in BMC Nephrology, with collaborators in the Division of Nephrology and Hypertension and senior author Edward D. Siew, M.D., of the Department of Bioinformatics, and partners at the University of Minnesota, including first author Bethany C. Birkelo, D.O.
The researchers conducted a retrospective, case-control study analyzing 6,996 adults with heart failure – 1,847 cases with reduced fraction and 5,149 control cases with preserved ejection fraction. All were diagnosed through the Vanderbilt Health system between 2008 and 2022.
They examined AKI events occurring in the two years prior to heart failure and adjusted for baseline characteristics, including vitals, comorbidities, and prior medication use.
Uncovering Associations
Brittain, Siew, and their team uncovered a statistically significant association between stage 1 kidney patients and those undergoing heart failure with preserved ejection fraction. In contrast, stages 2-3 kidney patients did not significantly show the heart-failure subtype associations but trended toward those displaying reduced ejection fraction.
“HFpEF is associated with a constellation of comorbidities, which may predispose patients to kidney dysfunction,” Brittain said. “Patients with a high comorbidity burden could be more susceptible to small fluctuations in serum creatinine during illness or hospitalization.”
“Our results highlight the importance of close follow-up and monitoring of cardiac function and volume status after a hospitalization complicated by even mild AKI.”
The research suggests that mild AKI may have a direct effect on the heart. Brittain explains that preclinical studies provide evidence that cardiac dysfunction may induce AKI, including diastolic dysfunction.
Concerning the second finding, they acknowledged that the small sample size may have precluded the ability to detect a significant association between severe AKI and heart failure with reduced ejection fraction.
“Greater severity of illness can result in reduced ejection fraction,” Brittain said. “For example, severe AKI can occur after a myocardial infarction with cardiogenic shock.”
Future studies with larger sample sizes are needed to investigate this potential association, they explained.
Clinical Implications
These findings have important clinical implications, Brittain noted.
“Our results highlight the importance of close follow-up and monitoring of cardiac function and volume status after a hospitalization complicated by even mild AKI,” he said.
“Patients who are hospitalized for AKI should be warned about the risk of developing heart failure down the line.”
Brittain hopes that these findings will better inform clinicians about the close relationship between AKI and heart failure.
“Patients who are hospitalized for AKI should be warned about the risk of developing heart failure down the line,” he added. “Extra fluid on the body is an early marker of heart failure.”
