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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study
Gregory L Hundemer1, Greg A Knoll1, William Petrcich2
1Department of Medicine (Division of Nephrology) and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
Insights
Alpha-blockers (ABs) increase kidney disease progression risk but lower cardiac event and mortality risks in patients with chronic kidney disease (CKD). This study clarifies ABs impact on CKD outcomes.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Alpha-blockers (ABs) are frequently prescribed for resistant hypertension, including in patients with chronic kidney disease (CKD).
- The impact of ABs on kidney, cardiac, mortality, and safety outcomes in CKD patients is not well understood.
Purpose of the Study:
- To investigate the association between new alpha-blocker (AB) use and kidney, cardiac, mortality, and safety outcomes in older adults with chronic kidney disease (CKD).
- To explore potential interactions between AB use and estimated glomerular filtration rate (eGFR) categories on these outcomes.
Main Methods:
- A population-based retrospective cohort study was conducted using data from Ontario, Canada residents aged 66 years and older (2007-2015).
- New users of ABs were matched 1:1 to new users of non-AB blood pressure-lowering medications using high-dimensional propensity scores.
- Cox proportional hazards and Fine and Gray models were employed to analyze associations with kidney function decline, kidney replacement therapy, cardiac events, mortality, and safety events.
Main Results:
- Alpha-blocker (AB) use was linked to an increased risk of significant estimated glomerular filtration rate (eGFR) decline (HR, 1.14) and need for kidney replacement therapy (HR, 1.28).
- Conversely, AB use was associated with a reduced risk of cardiac events (HR, 0.92) across all eGFR levels.
- Mortality risk was lower with AB use, particularly in patients with eGFR < 60 mL/min/1.73m² (P interaction < 0.001).
Conclusions:
- Alpha-blocker (AB) initiation in patients with chronic kidney disease (CKD) is associated with a higher risk of kidney disease progression.
- However, AB use demonstrates a lower risk of cardiac events and mortality compared to alternative blood pressure-lowering medications in this population.
- The findings suggest a complex risk-benefit profile for alpha-blockers in CKD management.
Rationale & Objectives:
Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown.
Study Design:
Population-based retrospective cohort study.
Settings & Participants:
Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB.
Exposures:
New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication.
Outcomes:
30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality.
Analytical Approach:
New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m2) were explored.
Results:
Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m2 (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m2, respectively.
Limitations:
Observational design, BP measurement data unavailable.
Conclusions:
AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.
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