RAS Inhibitor Effects Not Modified by Age

Patients with chronic kidney disease (CKD) are commonly treated with renin-angiotensin system inhibitors (RASi) to slow progression to kidney failures. Previous trials of the effectiveness and tolerance of RASi have often excluded older patients, resulting in a lack of data on effects on patients as they age.

Cédric Villain, MD, PhD, and colleagues conducted the CKD-REIN cohort study in a cohort of older patients with CKD stages 3 and 4 and a clinical indication for RASi. Results were reported online in the Journal of the American Medical Directors Association [doi:10.1016/jamda.2021.10.019].

The cohort included 2762 patients who were enrolled in the study between 2013 and 2016 in 40 nephrology clinical nationally representative in France. The primary outcome of interest was the occurrence of kidney failure or death. Secondary outcomes included the occurrence of cardiovascular events and hospitalizations with acute kidney injury (AKI) or hyperkalemia. The researchers performed a propensity score analysis and used Cox models to estimate hazard ratios (HRs) for each outcome associated with RASi prescription and tested interactions with age.

Mean age of the cohort was 67 years, including 841 patients (30%) ≥75 years of age. Of the total cohort, 79% (n=2178) were prescribed an RASi. Median follow-up was 4.6 years. During follow-up, 33% of patients reached the primary outcome of kidney failure or death. There was an association between RASi prescription and a lower risk of kidney failure or death (HR, 0.79; 95% confidence interval [CI], 0.66-0.95). The association was not modified by age (P for interaction =.72).

There was no significant association between RASi prescription and cardiovascular events. During the first 3 years of follow-up, 14% of patients were hospitalized with AKI or hyperkalemia; the risk was not higher among the group prescribed an RASi (HR, 0.75; 95% CI, 0.55-1.02) and age did not modify its effect (P for interaction =.28).

In conclusion, the authors said, “This study shows that aging does not appear to modify either RASi’s beneficial effects on major CKD outcomes or their potential adverse effects.”