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Renin-angiotensin system blocker discontinuation and adverse outcomes in chronic kidney disease
Carl P Walther1, Wolfgang C Winkelmayer1, Peter A Richardson2,3
1Department of Medicine, Section of Nephrology, Baylor College of Medicine, Selzman Institute for Kidney Health, Houston, TX, USA.
Insights
Discontinuing renin-angiotensin system inhibitors (RASIs) like ACEIs and ARBs in veterans with chronic kidney disease (CKD) significantly increases the risk of death and end-stage kidney disease (ESKD). Further research is needed to understand discontinuation causes.
Area of Science:
- Nephrology
- Pharmacology
- Public Health
Background:
- Renin-angiotensin system inhibitors (RASIs), including ACEIs and ARBs, are standard care for CKD with albuminuria.
- Treatment discontinuation is common, necessitating investigation into its impact on patient outcomes.
- This study focuses on US veterans with non-dialysis-dependent CKD.
Purpose of the Study:
- To investigate the association between ACEI/ARB discontinuation and adverse outcomes in US veterans with CKD.
- To quantify the risk of death and incident end-stage kidney disease (ESKD) following ACEI/ARB discontinuation.
Main Methods:
- Retrospective cohort study of 141,252 US veterans with CKD initiated on ACEI/ARB therapy.
- Discontinuation defined as a gap of ≥14 days; classified by duration (14-180+ days).
- Time-varying Cox proportional hazards models used to assess outcomes (death, ESKD), adjusting for confounders.
Main Results:
- ACEI/ARB discontinuation was associated with a significantly higher risk of death (HRs ranging from 1.74 to 2.3).
- Similar associations were observed for incident ESKD (HRs ranging from 1.47 to 1.65).
- The risk increased with longer durations of discontinuation.
Conclusions:
- ACEI/ARB discontinuation is independently linked to increased mortality and ESKD risk in veterans with CKD.
- Underlying illness severity may influence discontinuation decisions.
- Further research is crucial to identify causes of discontinuation and inform clinical practice.
Background:
Treatment with renin-angiotensin system inhibitors (RASIs), angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is the standard of care for those with chronic kidney disease (CKD) and albuminuria. However, ACEI/ARB treatment is often discontinued for various reasons. We investigated the association of ACEI/ARB discontinuation with outcomes among US veterans with non-dialysis-dependent CKD.
Methods:
We performed a retrospective cohort study of patients in the Veterans Affairs healthcare system with non-dialysis-dependent CKD who subsequently were started on ACEI/ARB therapy (new user design). Discontinuation events were defined as a gap in ACEI/ARB therapy of ≥14 days and were classified further based on duration (14-30, 31-60, 61-90, 91-180 and >180 days). This was treated as a time-varying risk factor in adjusted Cox proportional hazards models for the outcomes of death and incident end-stage kidney disease (ESKD), which also adjusted for relevant confounders.
Results:
We identified 141 252 people with CKD and incident ACEI/ARB use who met the inclusion criteria; these were followed for a mean 4.87 years. There were 135 356 discontinuation events, 68 699 deaths and 6152 incident ESKD events. Discontinuation of ACEI/ARB was associated with a higher risk of death [hazard ratio (HR) 2.3, 2.0, 1.99, 1.92 and 1.74 for those discontinued for 14-30, 31-60, 61-90, 91-180 and >180 days, respectively]. Similar associations were noted between ACEI and ARB discontinuation and ESKD (HR 1.64, 1.47, 1.54, 1.65 and 1.59 for those discontinued for 14-30, 31-60, 61-90, 91-180 and >180 days, respectively).
Conclusions:
In a cohort of predominantly male veterans with CKD Stages 3 and 4, ACEI/ARB discontinuation was independently associated with an increased risk of subsequent death and ESKD. This may be due to the severity of illness factors that drive the decision to discontinue therapy. Further investigations to determine the causes of discontinuations and to provide an evidence base for discontinuation decisions are needed.
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