TY - JOUR
T1 - Hyperkalemia and Acute Kidney Injury with Spironolactone Use Among Patients with Heart Failure
AU - Secora, Alex M.
AU - Shin, Jung Im
AU - Qiao, Yao
AU - Alexander, G. Caleb
AU - Chang, Alex R.
AU - Inker, Leslie A.
AU - Coresh, Josef
AU - Grams, Morgan E.
N1 - Funding Information:
Potential Competing Interests: Dr Shin is a principal investigator of a grant provided to the Johns Hopkins Bloomberg School of Public Health from Merck. Dr Alexander is past Chair of the US Food and Drug Administration's Peripheral and Central Nervous System Advisory Committee; has served as a paid advisor to IQVIA; serves as a consultant and holds equity in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation; and is a member of OptumRx's National P&T Committee. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. Dr. Inker has consulting agreements with Tricida and Omeros Corp. The remaining authors report no potential competing interests.Grant Support: Dr Secora was supported by grant T32 HL007024 from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH). Dr Gram is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01 DK100446 and R01 DK115534). Dr Alexander is supported by 1 U01 FD004977-02 from the U.S. Food and Drug Administration (FDA). Dr Chang is supported by a grant from the NIDDK (K23 DK106515). Dr Shin is supported by a grant from the NIDDK (K01 DK121825). Dr. Inker is supported by grants from NIDDK (R01DK115534 and U01DK085689), and funding from Retrophin, Omeros, Dialysis Clinics, Inc., and Reata Pharmaceuticals for research and contracts to Tufts Medical Center.
Funding Information:
Grant Support: Dr Secora was supported by grant T32 HL007024 from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH). Dr Gram is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ( R01 DK100446 and R01 DK115534 ). Dr Alexander is supported by 1 U01 FD004977-02 from the U.S. Food and Drug Administration (FDA). Dr Chang is supported by a grant from the NIDDK ( K23 DK106515 ). Dr Shin is supported by a grant from the NIDDK ( K01 DK121825 ). Dr. Inker is supported by grants from NIDDK (R01DK115534 and U01DK085689), and funding from Retrophin, Omeros, Dialysis Clinics, Inc., and Reata Pharmaceuticals for research and contracts to Tufts Medical Center.
Publisher Copyright:
© 2020
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.mayocp.2020.03.035
DO - 10.1016/j.mayocp.2020.03.035
M3 - Article
C2 - 33153631
AN - SCOPUS:85094889649
VL - 95
SP - 2408
EP - 2419
JO - Mayo Clinic Proceedings
JF - Mayo Clinic Proceedings
SN - 0025-6196
IS - 11
ER -