Effects of sodium bicarbonate, cholecalciferol, and protein supplementation interventions on muscle mass and metabolic disturbances in patients with chronic kidney disease: a systematic review and network meta-analysis

Abstract

Background: Patients with chronic kidney disease (CKD) often experience a decline in muscle mass and metabolic disturbances, which may increase the risk of cardiovascular events and all-cause mortality. Sodium bicarbonate, cholecalciferol, and protein supplementation are commonly used pharmacological and nutritional interventions; however, systematic evidence comparing their effects on muscle mass, metabolic status, and related outcomes in CKD patients remains lacking.

Methods: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to July 1, 2025, and included eligible comparative clinical studies. Conventional meta-analysis and network meta-analysis (NMA) were used to compare the three categories of interventions in outcomes such as muscle mass, muscle function, and serum metabolic parameters, and surface under the cumulative ranking curve (SUCRA) values were used to rank intervention effects.

Results: A total of 22 studies involving 2,879 patients were included, comprising 11 on sodium bicarbonate, 5 on cholecalciferol, and 6 on protein supplementation. Conventional meta-analysis indicated that sodium bicarbonate may be more effective in improving HCO₃^- and potassium levels in the early stage and may have certain effects on eGFR and systolic blood pressure at 24 months. NMA results showed that cholecalciferol was advantageous in increasing muscle mass (SMD = 0.68, 95% CI = 0.09 to 1.27), sodium bicarbonate performed better in improving serum albumin (SMD = 0.50, 95% CI = 0.01 to 0.99), and protein supplementation ranked highest for reducing serum phosphorus (SUCRA = 64.9%) and the incidence of adverse events (SUCRA = 71.9%). However, no significant differences were observed among the three interventions in muscle mass or serum metabolic parameters.

Conclusion: Sodium bicarbonate and cholecalciferol may have potential advantages in improving serum albumin and increasing muscle mass, respectively. While protein supplementation may offer some value in reducing serum phosphorus and the incidence of adverse events. Given the limited number of included studies, small sample sizes, and substantial heterogeneity in intervention protocols, these conclusions should be further validated in future large-scale, rigorously designed randomized controlled trials.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251126837, identifier PROSPERO (CRD420251126837).

Keywords: cholecalciferol; chronic kidney disease; metabolic disturbances; muscle mass; network meta-analysis; protein supplementation; sodium bicarbonate.