Efficacy and safety of ketoanalogue supplementation combined with protein-restricted diets in advanced chronic kidney disease: a systematic review and meta-analysis

Chen et al., 2024 | J Nephrol | Meta Analysis

Citation

Chen Chih-Heng, Tsai Ping-Hsiu, ... Wu Hon-Yen. Efficacy and safety of ketoanalogue supplementation combined with protein-restricted diets in advanced chronic kidney disease: a systematic review and meta-analysis. J Nephrol. 2024-Nov;37(8):2113-2125. doi:10.1007/s40620-024-02065-9

Abstract

BACKGROUND: The benefits and harms of protein-restricted diets supplemented with ketoanalogues in patients with chronic kidney disease (CKD) remain uncertain. We aimed to evaluate the effects of ketoanalogues supplemented to protein-restricted diets in patients with advanced CKD. METHODS: We conducted systematic literature searches of PubMed, Embase, Scopus, and Cochrane Library up to June 3, 2024. Randomized controlled trials comparing ketoanalogue supplementation with a low- or very low-protein diet versus a low-protein diet alone in stages 3-5 CKD patients were selected. Outcomes included glomerular filtration rate (GFR), end-stage kidney disease (ESKD), all-cause mortality, and blood levels of urea nitrogen, calcium, phosphorus, and albumin. Triceps skin fold, mid-arm muscle circumference, lean body mass, and subjective global assessment were also evaluated. The protocol for this systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42023465754). RESULTS: A total of 16 trials comprising 1344 participants were identified, with a median follow-up of 13 months. Compared to a low-protein diet alone, ketoanalogues supplemented to a protein-restricted diet resulted in a significantly higher GFR, decreased levels of urea nitrogen and phosphorus, and increased levels of calcium. Furthermore, ketoanalogues combined with a protein-restricted diet showed a marginally lower risk of ESKD in participants without diabetes. No significant differences were observed in all-cause mortality, albumin, mid-arm muscle circumference, lean body mass, and subjective global assessment. CONCLUSIONS: For stages 3-5 CKD patients, ketoanalogues combined with a protein-restricted diet may help postpone initiation of dialysis, improve calcium-phosphate homeostasis, and slow GFR decline, while maintaining a similar nutritional status and survival. Larger, long-term studies are needed to confirm these potential benefits, especially in CKD patients with diabetes.

Key Findings

A total of 16 trials comprising 1344 participants were identified, with a median follow-up of 13 months. Compared to a low-protein diet alone, ketoanalogues supplemented to a protein-restricted diet resulted in a significantly higher GFR, decreased levels of urea nitrogen and phosphorus, and increased levels of calcium. Furthermore, ketoanalogues combined with a protein-restricted diet showed a marginally lower risk of ESKD in participants without diabetes. No significant differences were observ

Outcomes Measured

• Requires manual extraction

Population

MeSH Terms

• Humans
• Diet, Protein-Restricted
• Renal Insufficiency, Chronic
• Dietary Supplements
• Glomerular Filtration Rate
• Keto Acids
• Treatment Outcome
• Randomized Controlled Trials as Topic
• Kidney Failure, Chronic

Evidence Classification

• Level: Meta Analysis
• Publication Types: Journal Article, Systematic Review, Meta-Analysis, Research Support, Non-U.S. Gov't
• Vertical: calcium

Provenance

• PMID: 39340710
• DOI: 10.1007/s40620-024-02065-9
• PMCID: Not in PMC
• Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09