Longitudinal impact of sodium bicarbonate therapy on health-related quality of life in pre-dialysis chronic kidney disease with metabolic acidosis: a pragmatic trial in Malaysia

PURPOSE: Metabolic acidosis (MA) is a complication of chronic kidney disease (CKD) and is associated with adverse clinical outcomes. This study evaluated longitudinal changes in health-related quality of life (HRQoL) among pre-dialysis CKD patients with MA following initiation of sodium bicarbonate therapy. METHODS: In this 18-month, single-centre, open-label, pragmatic trial, 74 adults with stage 3-4 CKD and MA (serum bicarbonate < 22 mmol/L) were allocated in a 1:1:1 ratio to receive oral sodium bicarbonate (tablets or solution) or standard care (control). HRQoL was assessed using the KDQOL-36 and EQ-VAS instruments. Longitudinal HRQoL trajectories and the effects of treatment and disease progression were evaluated using multivariable linear mixed-effects models. RESULTS: Baseline physical health was impaired across the cohort, with the Burden subscale scoring the lowest. Sodium bicarbonate increased serum bicarbonate levels during early titration, although only one-third of treated patients achieved the target range of 22-26 mmol/L. Neither sodium bicarbonate formulation significantly improved KDQOL-36 subscale or EQ-VAS scores compared with control. However, worsening CKD stage was significantly associated with lower HRQoL, with clinically meaningful declines observed in the KDQOL-36 Effects and Burden subscales. No significant differences were observed between treatment arms in blood pressure, body weight, or all-cause hospitalisations. Gastrointestinal symptoms and peripheral oedema were common among treated patients but were not significantly associated with HRQoL. CONCLUSION: Sodium bicarbonate therapy did not improve HRQoL in pre-dialysis CKD patients with MA. Patient-reported well-being appeared to be driven by CKD progression, highlighting the practical challenges and limitations of treat-to-target alkali therapy in routine clinical practice.