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Abstract: TH-PO1028

Association Between Reduced RAASi Therapy and Progression to ESKD in Hyperkalemic CKD Patients

Session Information

Category: CKD (Non-Dialysis)

  • 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention


  • Rastogi, Anjay, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States
  • Pollack, Charles, Department of Emergency Medicine, University of Mississippi School of Medicine, Jackson, Mississippi, United States
  • Lesén, Eva, CVRM Evidence, AstraZeneca, Gothenburg, Sweden
  • Agiro, Abiy, Renal Payer Evidence, AstraZeneca, Wilmington, Delaware, United States
  • Arnold, Matthew, Real World Science and Digital, AstraZeneca, Cambridge, United Kingdom
  • Morita, Naru, CVRM Medical Affairs, AstraZeneca, Osaka, Japan
  • Järbrink, Krister, CVRM Evidence, AstraZeneca, Gothenburg, Sweden
  • Murohara, Toyoaki, Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Kanda, Eiichiro, Department of Medical Science, Kawasaki Medical School, Okayama, Japan

Renin-angiotensin-aldosterone system inhibitor (RAASi) therapy is renoprotective in patients (pts) with chronic kidney disease (CKD) but increases hyperkalemia (HK) risk. Despite recommendations to maintain RAASi using novel anti-HK treatment, RAASi therapy is often limited/withdrawn in pts with HK. This observational study investigates risk of progression to end-stage kidney disease (ESKD) associated with HK-related RAASi reduction in CKD.


Data from hospital records/claims from the US (Optum’s de-identified Market Clarity Data) and Japan (Medical Data Vision) were analyzed. Pts with CKD Stage 3/4 and baseline RAASi use with an HK episode (ICD-10 code E87.5) during July 2019–Sept 2021 (US)/May 2020–Sept 2021 (Japan) were included. Based on RAASi prescriptions 3 months (mo) before vs after the HK episode, pts were categorized as down-titrated, discontinued, or maintained treatment. Risk of progression to ESKD (diagnosed CKD Stage 5/ESKD or dialysis initiation) within 6 mo in pts who down-titrated/discontinued vs maintained RAASi was assessed.


In total, 11,873 (US) and 1427 (Japan) pts were included. Mean age was 71 (US) and 76 (Japan) years; 52% and 66%, respectively, were male. In the US, 7506 pts filled a RAASi prescription within 3 mo prior to index event and had ≥3 mo follow-up; of these, 33% discontinued and 6% down-titrated. Of the corresponding 1179 pts in Japan, 27% discontinued and 5% down-titrated. Risk of progression to ESKD was 70–74% higher in all pts who discontinued, and 60% higher in US pts who down-titrated vs maintained RAASi (Table).


HK-prompted RAASi therapy reduction is associated with increased risk of progression to ESKD, indicating a need for improved guideline adherence in managing HK to maintain RAASi therapy.

Risk of progression to ESKD in patients with CKD Stage 3/4 who discontinued or down-titrated vs maintained RAASi therapy following an HK episode
CountryRAASi statusNEventsAdjusted HR (95% CI)P-value
Discontinued24601381.74 (1.37–2.21)<0.001
Down-titrated460231.60 (1.02–2.49)0.039
Discontinued323261.70 (1.01–2.86)0.045
Cox proportional hazards regression adjusted for age, sex, history of HK, diabetes, heart failure, CKD including stage, and baseline use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists.
This category was not included in the Cox regression analysis due to the low patient numbers.
CI, confidence interval; CKD, chronic kidney disease; ESKD end-stage kidney disease; HK, hyperkalemia; HR, hazard ratio; RAASi, renin-angiotensin-aldosterone system inhibitor; ref, reference group.


  • Commercial Support – AstraZeneca