The following is a summary of “VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients with Metabolic Acidosis,” published in the March 2024 issue of Nephrology by Tangri et al.

Metabolic acidosis is a common complication of CKD, which is associated with rapid decline of kidney function. However, no studies show how treating metabolic acidosis affects CKD progression. 

Researchers conducted a prospective study investigating the effect of veverimer, a novel hydrochloric acid binder that removes acid from the gastrointestinal tract and increases serum bicarbonate.

They randomized 1,480 CKD individuals (eGFR of 20-40 ml/min per 1.73 m²) and metabolic acidosis (serum bicarbonate of 12-20 mEq/L)  across 320 different sites to placebo or veverimer.  The primary outcome was the endpoint of CKD progression, including reaching end-stage kidney disease (ESKD), with a decline in eGFR of ≥40% from baseline or death due to kidney failure. 

The results showed that mean baseline eFR was 29.2±6.3 ml/min per 1.73m² with 17.5±1.4 mEq/L serum bicarbonate, which increased to 23.4±2.0 mEq/Lafter active treatment. During withdrawal, serum bicarbonate levels remained higher in the veverimer group (22.0±3.0 mEq/L) compared to placebo (20.9±3.3 mEq/L) from month 3 to 24 months. A primary endpoint event occurred between the two groups (149/741 and 148/739) with (HR 0.99, 95% CI, 0.8 – 1.2, P=0.90). 

Investigators concluded that veverimer did not slow CKD progression in patients with metabolic acidosis. The bicarbonate levels did not separate as much as expected, which made it difficult to test the hypothesis.

Source: journals.lww.com/jasn/abstract/2024/03000/valor_ckd__a_multicenter,_randomized,_double_blind.7.aspx