Real-World Findings Support RASi Continuation in Advanced CKD

Miriam E. Tucker, for Medscape

August 31, 2022

The study covered in this summary was published in Preprints with The Lancet and has not yet been peer reviewed.

Key Takeaways

  • In a real-world study, discontinuing renin-angiotensin-system inhibitors (RASi) in patients with type 2 diabetes and advanced chronic kidney disease (CKD) permanently or transiently is associated with an increased risk of major adverse cardiovascular events (MACE), heart failure (HF), and end-stage kidney disease (ESKD).

  • In accordance with international recommendations, actions should be taken to ensure continuation of RASi (including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) for organ protection with more frequent kidney function monitoring.

  • Pending randomized clinical trial data, RASi use should be continued in patients with an estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73m2 for cardiovascular–renal protection.

Why This Matters

  • Debates continue regarding the risk–benefits of RASi continuation in advanced CKD, with conflicting evidence.

  • In real-world practice, 15% to 30% of patients with CKD had RASi discontinued upon reaching eGFR < 30 mL/min/1.73m2, often due to dose-dependent hyperkalemia and/or acute eGFR decline.

  • The incidence of hyperkalemia in CKD stages G4-G5 is estimated at 30% and may be more common in people with diabetes.

  • The Kidney Disease Improving Global Outcomes (KDIGO) 2020 guidelines on diabetes in CKD recommended continuation of RASi unless serum creatinine level increases above 30% within 4 weeks of initiation, and discontinuation only if hyperkalemia is refractory to medical treatment or dose reduction.

Study Design

  • Population-based cohort study of 10,400 patients with type 2 diabetes in Hong Kong with new-onset eGFR < 30 mL/min/1.73m2, of whom 1766 (17.0%) discontinued and 8634 (83%) continued RASi therapy.

Key Results

  • Median time from follow-up to death was 4.1 years for discontinued-RASi users and 3.6 years for continued-RASi users.

  • Respective crude incidences per 1000 person-years (95% CI) for discontinued and continued RASi users were:

    • MACE: 29.1 (25.5 - 33.1) vs 34.9 (33.0 - 37.0)

    • HF: 22.1 (18.9 - 25.6) vs 34.8 (32.8 - 36.8)

    • ESKD: 61.7 (56.1 - 67.7) vs 82.2 (78.9 - 85.5)

    • All-cause mortality: 84.4 (78.3 - 90.8) vs 83.4 (80.5 - 86.5).

  • Compared with continued RASi, discontinued RASi was associated with the following weighted and adjusted hazard ratios (95% CI):

    • MACE: 1.26 (1.07 - 1.48)

    • HF: 1.85 (1.52 - 2.25)

    • ESKD: 1.29 (1.17 - 1.43)

    • All-cause mortality: 0.95 (0.87 - 1.03) (ie, neutral).

  • After balancing group characteristics, there was a neutral risk of first-event hyperkalemia in discontinued versus continued RASi users (0.95, 0.84 - 1.08).


  • RASi dose, drug adherence, and concomitant drug use were not considered.

  • Potential residual confounding.


  • Study funding: CUHK Impact Research Fellowship Scheme.

  • Author disclosures: Several authors have multiple pharmaceutical company disclosures.

This is a summary of a preprint research study , "Discontinuation of RASi and clinical events in advanced chronic kidney disease: A prospective cohort study in 10,400 patients with type 2 diabetes," written by Aimin Yang, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China, and colleagues published on Preprints with The Lancet and provided to you by Medscape. The study has not yet been peer reviewed.


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