RAASi Discontinuation for Hyperkalemia May Increase Adverse Outcomes

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For patients with chronic kidney disease (CKD), discontinuing renin-angiotensin-aldosterone system inhibitors (RAASi) during episodes of hyperkalemia is associated with increased mortality and cardiovascular events, reports a pre-proof paper in the American Journal of Kidney Diseases.

The retrospective study included data on adult CKD patients with new episodes of RAASi-related hyperkalemia with a serum potassium level 5.5 mM or higher. Drawn from Canadian provincial databases, the analysis included 7200 patients in Manitoba and 71,290 patients in Ontario. The mean ages were 72.39 and 79.48 years, respectively. Several types of comorbidity were more frequent in the Manitoba cohort.

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For patients with chronic kidney disease (CKD), discontinuing renin-angiotensin-aldosterone system inhibitors (RAASi) during episodes of hyperkalemia is associated with increased mortality and cardiovascular events, reports a pre-proof paper in the American Journal of Kidney Diseases.

The retrospective study included data on adult CKD patients with new episodes of RAASi-related hyperkalemia with a serum potassium level 5.5 mM or higher. Drawn from Canadian provincial databases, the analysis included 7200 patients in Manitoba and 71,290 patients in Ontario. The mean ages were 72.39 and 79.48 years, respectively. Several types of comorbidity were more frequent in the Manitoba cohort.

In response to hyperkalemia, RAASi therapy was discontinued in 35.08% of patients in the Manitoba cohort versus 14.0% in the Ontario cohort. On Cox proportional hazards analysis, RAASi discontinuation was associated with increased all-cause mortality: hazard ratio (HR) 1.32 in Manitoba and 1.47 in Ontario. Discontinuation was also linked to higher cardiovascular mortality: HR 1.28 in Manitoba and 1.32 in Ontario.

Associations were also noted for fatal and nonfatal cardiovascular events: HR 1.17 in Manitoba and 1.18 in Ontario. An association between RAASi discontinuation and risk of dialysis initiation was significant in the Ontario cohort: HR 1.11. Use of a submaximal RAASi dose was also associated with increased all-cause mortality compared with a maximal dose: HR 1.24 in Manitoba and 1.11 in Ontario.

Although RAASi are recommended as first-line therapy for CKD, they are also associated with increased risk of hyperkalemia. There is no accepted standard of care for chronic hyperkalemia in CKD patients. As shown by these Canadian data, RAASi discontinuation or dose reduction is a common strategy.

The study shows that among CKD patients with hyperkalemia, RAASi discontinuation is associated with increased all-cause mortality and cardiovascular events. “Newer medications for the treatment of hyperkalemia may enable patients to continue their RAASi after an episode of hyperkalemia,” the investigators conclude [Leon SJ, 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, published online ahead of print January 24, 2022. doi: 10.1053/j.ajkd.2022.01.002; https://www.ajkd.org/article/S0272-6386(22)00034-8/fulltext].

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