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Hyperkalemia and Acute Kidney Injury with Spironolactone Use Among Patients with Heart Failure

  • Alex M. Secora
    Correspondence
    Correspondence: Address to Alex M. Secora, PhD, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205.
    Affiliations
    Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD

    Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD
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  • Jung-Im Shin
    Affiliations
    Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD

    Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD
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  • Yao Qiao
    Affiliations
    Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD

    Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD
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  • G. Caleb Alexander
    Affiliations
    Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD

    Division of General Internal Medicine, Department of Medicine, Johns Hopkins Medicine, Baltimore, MD
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  • Alex R. Chang
    Affiliations
    Division of Nephrology, Geisinger Health System, Danville, PA
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  • Leslie A. Inker
    Affiliations
    Tufts Medical Center, Department of Internal Medicine, Division of Nephrology, Boston, MA
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  • Josef Coresh
    Affiliations
    Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD

    Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD
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  • Morgan E. Grams
    Affiliations
    Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD

    Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD

    Division of Nephrology, Department of Medicine, Johns Hopkins Medicine, Baltimore, MD
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      Abstract

      Objective

      To quantify the risk of hyperkalemia and acute kidney injury (AKI) when spironolactone use is added on to loop diuretic use among patients with heart failure, and to evaluate whether the risk is modified by level of kidney function.

      Methods

      We identified 17,110 patients with heart failure treated with loop diuretics between January 1, 2004, and December 31, 2016 within the Geisinger Health System. We estimated the incidence of hyperkalemia and AKI associated with spironolactone initiation, and used target trial emulation methods to minimize confounding by indication.

      Results

      During a mean follow-up of 134 mo, 3229 of 17,110 patients (18.9%) initiated spironolactone. Incidence rates of hyperkalemia and AKI in patients using spironolactone with a loop diuretic were 2.9 and 10.1 events per 1000 person-months, respectively. In propensity score–matched analyses, spironolactone initiation was associated with higher hyperkalemia and AKI risk compared with loop alone (hazard ratio, 1.69; 95% CI, 1.35 to 2.10; P<.001, and hazard ratio, 1.12; 95% CI, 1.00 to 1.26; P=.04, respectively). There were no differences in the relative risk of either outcome associated with spironolactone by level of kidney function.

      Conclusion

      The addition of spironolactone to loop diuretics in patients with heart failure was associated with higher risk of hyperkalemia and AKI; these risks must be weighed against the potential benefits of spironolactone.

      Abbreviations and Acronyms:

      ACEi (angiotensin-converting enzyme inhibitor), ARB (angiotensin II receptor blockers), AKI (acute kidney injury), CVD (cardiovascular disease), CCI (Charlson comorbidity index), CKD (chronic kidney disease), eGFR (estimated glomerular filtration rate), EHR (electronic health record), HFpEF (heart failure with preserved ejection), HFrEF (heart failure with reduced ejection), ITT (intention-to-treat), K (potassium), PAD (peripheral artery disease), PS (propensity score), RALES (Randomized Aldactone Evaluation Study), SCr (serum creatinine), sHR (subdistribution hazard ratios), TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist)
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