Patients with nondialysis-dependent chronic kidney disease (CKD) reap cardiovascular and renal benefits from using renin-angiotensin–aldosterone-system (RAAS) inhibitors, but they are at high risk for hyperkalemia due to these medications, CKD, and comorbid diabetes and heart failure. The benefits of continuing RAAS inhibitor use appear to outweigh the risks. A new study finds that halting a RAAS inhibitor after a hyperkalemia episode increases the risks for death, cardiovascular events, and dialysis initiation.

Investigators studied 2 Canadian CKD cohorts with estimated glomerular filtration rates (eGFR; in mL/min/1.73 m2) less than 60 who were treated with RAAS inhibitors at the time of a de novo hyperkalemia episode (defined as a serum potassium level of 5.5 mmol/L or higher). The Manitoba cohort included 7200 adults aged 18 years or older, whereas the Ontario cohort included 71,290 adults older than 65 years. At baseline, mean serum potassium levels were 5.8 and 5.7 mEq/L in Manitoba and Ontario, respectively.

Compared with drug continuation, RAAS inhibitor discontinuation was significantly associated with 32% and 47% higher risks for all-cause mortality in Manitoba and Ontario, respectively, after adjustment, Navdeep Tangri, MD, PhD, of Seven Oaks General Hospital in Winnipeg, Manitoba, Canada, and colleagues reported in the American Journal of Kidney Diseases. Cardiovascular mortality risk was significantly increased by 28% and 32% after discontinuation, respectively.

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RAAS inhibitor discontinuation also was significantly associated with a 17% and 18% increased risk for cardiovascular events (both fatal and nonfatal) and a 65% and 11% increased risk for dialysis initiation in the 2 cohorts, respectively.

Approximately 35% of patients in Manitoba and 40% of patients in Ontario were receiving a maximal dose of a RAAS inhibitor at the time of hyperkalemia. Of those, 12.3% and 14.5%, respectively, reduced their dose and 32% and 11%, respectively, discontinued the drug. Compared with drug continuation, both dose reduction and drug discontinuation increased the risks for death.

The results of this study are similar to a 2020 analysis of patients with an eGFR of 30 or less, published in the Journal of the American Society of Nephrology.

“Clinical trials have demonstrated the efficacy of RAASi in patients with kidney disease. This may suggest that whenever possible, healthcare providers should consider continuing the RAASi at target doses after an episode of hyperkalemia,” Dr Tangri’s team stated. The investigators noted that newer potassium binders may enable patients to continue a RAAS inhibitor after a hyperkalemia episode.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Leon SJ, Whitlock R, Rigatto C, et al. Hyperkalemia-related discontinuation of renin-angiotensin-aldosterone system inhibitors and clinical outcomes in CKD: a population-based cohort study. Am J Kidney Dis. doi:10.1053/j.ajkd.2022.01.002