Hyperkalemia continues to lead to discontinuation or down-titration of renin-angiotensin-aldosterone system inhibitors (RAASi) with serious consequences such as longer hospitalization, investigators reported at the European Renal Association’s 2023 congress in Milan, Italy.

Eiichiro Kanda, MD, PhD, MPH, of Kawasaki Medical School in Okayama, Japan, and colleagues presented contemporary data from the ZORA study including 25,963 patients from the United States and 8722 patients from Japan with chronic kidney disease and/or heart failure who experienced hyperkalemia. The vast majority, 85% and 91%, respectively, had been taking RAASi prior to their hyperkalemia episode.

Following the hyperkalemia episode, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEi/ARB) were discontinued in 23%-26% of users and mineralocorticoid receptor antagonists (MRA) in 33%-46% of users. Only 10%-15% of American patients and 6%-8% of Japanese patients re-initiated RAASi within 6 months, the investigators reported. Among patients who re-initiated RAASi, 17% to 37% of patients in both the US and Japan had their dose of ACEi/ARB or MRA reduced by more than 25%.

Continue Reading

In a related study, the investigators propensity-score matched cardiorenal patients from Sweden and Japan who did and did not reduce RAASi treatment after a hyperkalemia episode. All-cause hospital length of stay was 18.2 days longer in Sweden and 17.9 days longer in Japan after a hyperkalemia episode in those who decreased RAASi use, Dr Kanda’s team reported. Length of stay was only 9.4 and 8.5 days longer in Sweden and Japan, respectively, for those who resumed their usual RAASi dose. The investigators observed similar patterns in subgroup analyses of patients with CKD or heart failure.

The research teams also recently reported that hyperkalemia-related RAASi changes were associated with higher risks of cardiorenal events.

“These powerful real-world data show how common it is for hyperkalaemia to cause down-titration of guideline-recommended RAASi therapy in cardiorenal patients,” co-investigator Anjay Rastogi, MD, PhD, Clinical Chief of Nephrology at UCLA Health, said in a statement. “Hyperkalaemia should not be a barrier to patients with chronic kidney disease or heart failure achieving guideline directed RAASi treatment, especially when there are treatment options, like potassium binders, which may better manage this chronic condition.”

Disclosure: This research was supported by AstraZeneca. Please see the original reference for a full list of disclosures.


1. Kanda E, Pollack C, Rastogi A, et al. Suboptimal Extent of RAASi Re-Initiation After Discontinuation Following Hyperkalemia: an Observational Study of Cardiorenal Patients in US and Japan. Presented at: ERA 2023 Congress; 2023 June 15-18; Milan, Italy. Abstract 3303.

2. Svensson M, Murohara T, Sundström J, et al. Increase in hospitalized days after hyperkalemia-related reduction in RAASi use: An observational study on cardiorenal patients in Sweden and Japan. Presented at: Presented at: ERA 2023 Congress; 2023 June 15-18; Milan, Italy. Abstract 4406.

3. Real-world evidence study shows the significant impact of hyperkalaemia on cardiorenal patient outcomes. News release. AstraZeneca; June 17, 2023.