Reductions in RAASi Therapy and Risk of ESKD in Patients With Hyperkalemia

Therapy with renin-angiotensin-aldosterone system inhibitors (RAASi) confers renoprotective benefits on patients with chronic kidney disease, but increases the risk for hyperkalemia. Guideline recommendations call for maintenance of RAASi therapy using novel antihyperkalemia treatment. However, according to Anhay Rastogi and colleagues, RAASi therapy is often limited or withdrawn in patients with hyperkalemia.

The researchers conducted an observational study to examine the risk of progression to end-stage kidney disease (ESKD) associated with hyperkalemia-related RAASi therapy reduction in patients with CKD. Results were reported during a poster session at the American Society of Nephrology Kidney Week 2023 in a poster titled Association Between Reduced RAASi Therapy and Progression to ESKD in Hyperkalemia CKD Patients.

The study utilized data from hospital records and claims from the United States (Optum’s deidentified Market Clarity Data) and Japan (Medical Data Vision). Eligible patients were individuals with CKD stage 3/4 and baseline RAASi use with an International Classification of Diseases, Tenth Revision code for hyperkalemia during July 2019 to September 2021 for the US cohort and May 2020 to September 2021 for the Japanese cohort.

Based on RAASi prescriptions 3 months prior to the index hyperkalemic episode versus after the episode, patients were categorized as down-titrated, discontinued, or maintained treatment. ESKD was defined as diagnosis of CKD stage 5 or ESKD. The study compared the risk of progression to ESKD within 6 months in patients who down-titrated or discontinued RAASi therapy with those who maintained RAASi therapy.

The cohorts included 11,873 (US) and 1427 (Japan) patients. Mean age was 71 years in the United States and 76 years in Japan. The US cohort was 52% male and the Japanese cohort was 66% male. In the US cohort, 7506 patients filled a prescription for an RAASi within 3 months prior to the index event and had ≥3 months of follow-up. Of those, 33% discontinued and 6% down-titrated. Among the corresponding patients in Japan (n=1179), 27% discontinued and 5% down-titrated.

The risk of progression to ESKD was 70% to 74% higher in all patients who discontinued, and 60% higher in patients in the US cohort who down-titrated versus those who maintained RAASi therapy.

“Hyperkalemia-promoted RAASi therapy reduction is associated with increased risk of progression to ESKD, indicating a need for improved guideline adherence in managing hyperkalemia to maintain RAASi therapy,” the researchers said.

Source: Rastogi A, Pollack C, Lesén E, et al. Association between RAASi therapy and progression to ESKD in hyperkalemic CKD patients. Th-PO1028. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2023; November 2, 2023; Philadelphia, Pennsylvania. Funding was provided by AstraZeneca plc.