No ACE in the Hole for Advanced Chronic Kidney Disease

Volume 22, Issue 1

Chronic kidney disease (CKD) continues to affect a large number of Americans and impart significant morbidity and mortality. As CKD advances, patients can progress to needing dialysis, which further reduces quality of life and increases short-term mortality unless a kidney transplant can be obtained.

Recently, several new medications have been developed for slowing the progression of CKD. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are now indicated for CKD regardless of the presence of diabetes, and finerenone was approved by the US Food and Drug Administration to reduce the risk of renal function decline, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adult patients with CKD associated with type 2 diabetes.

Despite these recent advances, renin-angiotensin-aldosterone system (RAAS) inhibitors remain the first-line therapy for slowing the progression of CKD. However, most of the data for using RAAS inhibitors comes from patients with mild to moderate CKD.

In this week’s issue of Talking Therapeutics, we explore a new study evaluating the use of RAAS inhibitors to slow disease progression in patients with advanced CKD.

Point 1: No ACE in the Hole After all

In this new trial, participants with advanced and progressive chronic kidney disease (estimated glomerular filtration rate [eGFR], <30 mL per minute per 1.73 m² of body-surface area) were randomly assigned to discontinue or continue therapy with RAAS inhibitors. Researchers evaluated patients’ eGFR at 3 years.

After 3 years, the change in eGFR was essentially the same between patients who either discontinued or continued RAAS inhibitors (12.6±0.7 mL/min/m² vs 13.3±0.6 mL/min/m²; P=0.42). End-stage kidney disease or the initiation of renal-replacement therapy was also similar between groups, occurring in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (hazard ratio, 1.28; 95% CI, 0.99 to 1.65). Adverse events occurred at a similar rate between groups.

Point 2: RAAS Inhibitors Still Likely to Be Used Extensively

While the results of this study are somewhat surprising and disappointing, RAAS inhibitors wilb0e used extensively as a blood pressure therapy in patients with advanced kidney disease. Many of these patients have very resistant hypertension, often requiring 3 or more medications to maintain a healthy blood pressure. RAAS inhibitors are first-line agents for managing hypertension, so even though they may not slow disease progression, they are still likely to be used for other indications in patients with advanced CKD.