Abstract
Metabolic acidosis is a common complication of chronic kidney disease (CKD). Veverimer is an orally administrated, free amine polymer with high capacity and binding selectivity to hydrochloric acid from the gastrointestinal tract. This study pooled the current evidence of the efficacy and safety of veverimer for the treatment of metabolic acidosis associated with CKD. We conducted a systematic literature search on PubMed, Embase, and Cochrane Central for relevant randomized controlled trials (RCTs) in June 2020. In this study, three RCTs with 548 patients were included in our analysis. The analysis revealed that veverimer was associated with increased bicarbonate level of patients (weight mean difference [WMD] 3.08, 95% confidence interval [CI] [2.40, 3.77], p < 0.001) and improved physical function compared with placebo measured by Kidney Disease and Quality of Life Short Form 36, question 3 (physical functioning domain) (KDQoL-PFD) score (WMD 5.25, 95% CI [1.58, 8.92], p = 0.005). For safety outcomes, both groups exhibited similar risks for developing headache, diarrhea, flatulence, and hyperkalemia. In conclusion, current clinical evidence indicates that veverimer is efficacious and safe against metabolic acidosis related to CKD compared with placebo. Further research comparing long-term veverimer use with traditional alkali therapy is needed.
Highlights
Chronic kidney disease (CKD) is a long-term structural or functional disorder of the kidneys, manifested by elevated serum levels of creatinine, cystatin C, or blood urea nitrogen (Drawz and Rahman, 2015)
Previous studies have shown that chronic disturbances in serum acid excretion with increased serum bicarbonate are related to increased risk for renal disease progression, heart failure, and allcause mortality (Shah et al, 2009; Menon et al, 2010; Raphael et al, 2011; Dobre et al, 2013)
After excluding 74 duplicate studies and 984 non-randomized controlled trials (RCTs) studies, 131 articles remained. Of these 131 studies, three double-blinded RCTs (Bushinsky et al, 2018; Wesson et al, 2019a; Wesson et al, 2019b) were included in the quantitative analysis
Summary
Chronic kidney disease (CKD) is a long-term structural or functional disorder of the kidneys, manifested by elevated serum levels of creatinine, cystatin C, or blood urea nitrogen (Drawz and Rahman, 2015). Metabolic acidosis is a common and persistent complication of CKD, which contributes to the continued progression of CKD. It is associated with a decrease in total renal ammonium excretion, titratable acid excretion, and bicarbonate reabsorption as a result of a decline in glomerular filtration rate (GFR) (Kraut and Madias, 2016). Previous studies have shown that chronic disturbances in serum acid excretion with increased serum bicarbonate are related to increased risk for renal disease progression, heart failure, and allcause mortality (Shah et al, 2009; Menon et al, 2010; Raphael et al, 2011; Dobre et al, 2013)
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