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

Why It Matters

The findings help clinicians prioritize adjunctive therapies for CKD‑related sarcopenia and metabolic imbalance, while highlighting the need for larger trials to confirm comparative benefits.

Key Takeaways

• Cholecalciferol showed the highest SUCRA for muscle mass increase
• Sodium bicarbonate ranked best for raising serum albumin in CKD
• Protein supplements ranked highest for lowering serum phosphorus levels
• No intervention significantly improved overall muscle function or eGFR
• Study limited by small sample sizes and heterogeneous protocols

Pulse Analysis

Chronic kidney disease is increasingly recognized as a driver of sarcopenia, metabolic acidosis, and mineral‑bone disturbances that elevate cardiovascular risk. Clinicians often turn to alkali therapy, vitamin D3, or protein enrichment to counteract these sequelae, yet head‑to‑head evidence has been scarce. By aggregating data from 22 comparative studies, this network meta‑analysis offers a rare side‑by‑side view of three widely used interventions, shedding light on how each targets distinct pathophysiological pathways—acid‑base correction, vitamin D‑mediated bone health, and nitrogen balance support.

The analysis revealed that cholecalciferol produced the most robust gain in muscle mass, reflected by a standardized mean difference of 0.68 and the highest SUCRA ranking among the three treatments. Sodium bicarbonate, while not improving muscle size, emerged as the top option for boosting serum albumin, an important marker of nutritional status. Protein supplementation, on the other hand, showed the greatest probability of reducing serum phosphorus and lowering adverse‑event rates, suggesting a role in managing mineral metabolism and treatment tolerability. Notably, none of the interventions delivered statistically significant improvements in muscle function tests, eGFR, or long‑term blood‑pressure control, underscoring the complexity of CKD‑related muscle wasting.

For practitioners, the data suggest a tailored approach: consider vitamin D3 for patients where muscle preservation is paramount, sodium bicarbonate when hypoalbuminemia dominates, and protein supplements for those at risk of hyperphosphatemia or treatment‑related complications. However, the modest sample sizes, varied dosing regimens, and high heterogeneity limit definitive conclusions. Future large‑scale, randomized trials with standardized protocols are essential to validate these rankings and to explore combination strategies that might synergistically address CKD’s multifactorial muscle and metabolic challenges.