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Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease : A
Elaine Ku1, Lesley A Inker2, Hocine Tighiouart3
1Departments of Medicine and Pediatrics, Division of Nephrology, and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (E.K.).
Background:
In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear.
Purpose:
To examine the association of ACEi or ARB treatment initiation, relative to a non-ACEi or ARB comparator, with rates of KFRT and death.
Data Sources:
Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023.
Study Selection:
Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2.
Data Extraction:
The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m2), albuminuria (urine albumin-creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes.
Data Synthesis:
A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m2, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all).
Limitation:
Individual participant-level data for hyperkalemia or acute kidney injury were not available.
Conclusion:
Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD.
Primary Funding Source:
National Institutes of Health. (PROSPERO: CRD42022307589).
Insights
Initiating angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB) significantly lowers kidney failure risk in advanced chronic kidney disease (CKD). However, these therapies do not appear to reduce the risk of death in this patient population.
Area of Science:
- Nephrology
- Pharmacology
- Clinical Trials
Background:
- The impact of initiating angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB) on kidney failure with replacement therapy (KFRT) and mortality in advanced chronic kidney disease (CKD) is not well-defined.
- Patients with advanced CKD often face a high risk of KFRT and death, necessitating clear therapeutic guidelines.
Purpose of the Study:
- To investigate the association between initiating ACEi or ARB treatment versus non-ACEi/ARB comparators and the rates of KFRT and death in patients with advanced CKD.
- To provide evidence-based guidance for the use of ACEi and ARB in managing advanced CKD.
Main Methods:
- A systematic review and meta-analysis of completed randomized controlled trials (RCTs) was conducted using data from Ovid Medline and the CKD Epidemiology Collaboration Clinical Trials Consortium up to December 31, 2023.
- Included RCTs involved patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2, comparing ACEi or ARB to placebo or other antihypertensive drugs.
- Primary outcome was KFRT; secondary outcome was death. Cox proportional hazards models were used for analysis, with subgroup analyses based on age, eGFR, albuminuria, and diabetes history.
Main Results:
- The analysis included 1739 participants from 18 trials, with a mean eGFR of 22.2 mL/min/1.73 m2 and a median follow-up of 34 months.
- Initiation of ACEi or ARB therapy was associated with a significantly reduced risk of KFRT (adjusted hazard ratio, 0.66; 95% CI, 0.55 to 0.79).
- No significant reduction in the risk of death was observed (hazard ratio, 0.86; 95% CI, 0.58 to 1.28), and no significant interactions were found across subgroups.
Conclusions:
- Initiating ACEi or ARB therapy demonstrates a protective effect against kidney failure with replacement therapy in patients with advanced chronic kidney disease.
- These medications do not appear to reduce the risk of death in this patient population.
- Further research may explore specific subgroups or alternative outcome measures, though current data suggest a clear benefit for KFRT prevention.
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