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Risk of Initiating ACE Inhibitors/ARBs in Advanced CKD
Quick Takes
- In patients with advanced CKD, initiation of an ACEi or ARB protects against the need for kidney failure replacement therapy compared to other antihypertensive therapies.
- Patients with advanced CKD incur no survival benefit from initiation of ACEi or ARB initiation.
- There was no benefit of discontinuing ACEi or ARB therapy in patients with advanced CKD regarding kidney or survival outcomes.
Study Questions:
Can patients with advanced chronic kidney disease (CKD) be initiated on angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARBs) without increasing their risk for needing kidney failure replacement therapy?
Methods:
A systematic meta-analysis of randomized controlled trials was performed from the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium, which focused on CKD progression between January 1946 and December 2023 to analyze data of participants with advanced CKD, defined as having an estimated glomerular filtration rate (eGFR) of 15-29 mL/min/1.73 m2 (stage 4 and 5) to determine their risk for developing kidney failure replacement therapy (dialysis). Of the original 71 trials screened, 18 trials met inclusion criteria. Cox-proportional hazards regression models examined the association between ACEi or ARB initiation, compared with placebo or other antihypertensive agents, to the primary outcome of kidney failure replacement therapy and the secondary outcome of death before the onset of kidney failure replacement therapy or a composite outcome of kidney failure replacement therapy or death.
Results:
The participants (n = 1,739) represented a mean age of 54.9 years, 51.9% were women, and 14.8% were Black. The median eGFR was 23 mL/min/1.73 m2 (interquartile range, 18-27 mL/min/1.73 m2), and 31.9% had an eGFR below 20 mL/min/1.73 m2. The median albumin-creatinine ratio was 1215 mg/g and 84.4% had severe albuminuria. The mean systolic blood pressure was 155.4 mm Hg, 21.2% had a history of coronary artery disease, and 37.6% had diabetes. Over a mean trial follow-up of 34 months, 35.9% developed kidney failure replacement therapy and 7.6% died. In adjusted analyses, ACEi or ARB treatment initiation resulted in a 34% lower risk for progression to kidney failure replacement therapy (hazard ratio, 0.66; 95% confidence interval, 0.55-0.79) than in the placebo or other antihypertensives group. There was no significant effect of ACEi or ARB initiation on the risk for death, which did not vary by age, eGFR, albuminuria, or diabetes for the outcome of kidney failure replacement therapy or death.
Conclusions:
The initiation of ACEi or ARBs, compared to other antihypertensive therapies, protects patients in advanced CKD against the risk for kidney failure replacement therapy; but the initiation was not associated with a lower risk against death.
Perspective:
Often patients with advanced CKD are excluded from clinical trials or not initiated on ACEi/ARBs in clinical practice due to a perceived risk of developing worse outcomes. This study brings insight into whether decisions to initiate ACEi or ARB for guideline-directed medical therapy should be based on a patient’s CKD stage or overall risk/benefit for kidney disease progression that could potentially delay the need for dialysis and reduce overall health care cost burden.
The association of the survival risks with ACEi and ARB initiation may have not been fully explored due to limited data reported in many trials regarding comorbidities, the incidence of hyperkalemia, nonfatal cardiovascular endpoints and cardiovascular deaths. In addition, the shared decision-making discussions regarding initiation or discontinuation of ACEi or ARB, or the pursuit of kidney failure replacement therapy was not clear in many trials, which may have led to nonadherence or biases in the results.
Clinical Topics: Cardiovascular Care Team, Prevention
Keywords: Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Antagonists, Kidney Failure, Chronic
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