Metabolic acidosis is associated with progression of CKD and impaired physical function. Veverimer – a novel hydrochloric-acid binder that removes acid from the gastrointestinal tract leading to an increase in serum bicarbonate – has been developed to treat metabolic acidosis with the goal of slowing progression of CKD. The VALOR-CKD trial (NCT03710291) is an international, randomised, multicentre, double-blind, placebo-controlled study evaluating the effect of veverimer QD on disease progression in patients with metabolic acidosis and CKD. Eligible patients had serum bicarbonate in the range of 12–20 mmol/L and an estimated glomerular filtration rate of 20–40 mL/min/1.73m2. Patients with acute metabolic acidosis who received a kidney transplant or scheduled renal replacement therapy within 6 months and acute kidney injury or anuria were excluded. The primary outcome of the study was CKD progression defined as the development of end-stage renal disease, a sustained decline in estimated glomerular filtration rate >40% from baseline, or death due to kidney failure. Key secondary endpoints included effects on physical function. Overall, 1,480 patients were randomised to veverimer 3–9 g QD (n=741) or placebo (n=739). Baseline characteristics were well balanced. There were 149 events with veverimer and 148 events with placebo (HR 0.99; 95% CI 0.78–1.24; P=0.898). Similarly, there was no difference in self-reported or objectively measured physical function, time to dialysis or renal death or cardiovascular death, nor any other secondary endpoint. No significant increases in serious adverse events were seen with veverimer compared with placebo. Regarding these disappointing results, Dr Navdeep Tangri (Seven Oaks General Hospital, Winnipeg, Canada) postulated that the bicarbonate levels in patients who were randomised to placebo (21 mEq/L approx.) may have limited the ability of the researchers to achieve a clinical or biochemical benefit from correction of metabolic acidosis [1].
- Tangri N, et al. VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients With Metabolic Acidosis. FR-OR65, ASN Kidney Week 2022, 3–6 Nov.
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