#1519 Nutritional impact of ketoanalogue supplementation with protein-restricted diets in advanced chronic kidney disease

Abstract Background and Aims The benefits and risks of a protein-restricted diet supplemented with ketoanalogues (KA) in patients with chronic kidney disease (CKD) are still being explored. Combining KA supplementation with a protein-restricted diet may potentially preserve the glomerular filtration rate (GFR) in CKD patients. However, concerns about protein-energy wasting and the nutritional benefits of KA supplementation remain uncertain. Previous systematic reviews have often included crossover or non-randomized studies and combined data from CKD and dialysis patients, potentially introducing heterogeneity when assessing the effects of KA supplementation in CKD patients. We aim to provide an updated and comprehensive assessment of the impact of combining KA supplementation with a protein-restricted diet on the nutritional status of advanced CKD patients compared to the effects of a protein-restricted diet alone. Method We conducted systematic literature searches of PubMed, Embase, Scopus, and Cochrane Library up to September 2023. We selected parallel-design randomized controlled trials comparing KA supplementation to a low- or very low-protein diet (VLPD) versus a low-protein diet (LPD) alone in adults with stages 3-5 CKD. Outcomes included serum albumin, triceps skinfold (TSF), and mid-arm muscle circumference (MAMC). Pooled estimates of effect measures were calculated using the random-effects model and presented as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Given the variation in CKD stages among the included studies, subgroup analyses were conducted based on baseline renal function (GFR < 20 vs. ≥ 20 mL/min/1.73 m²). To assess the robustness of our meta-analyses, we conducted sensitivity analyses by excluding studies with an in-trial follow-up duration of less than one year. Results We identified 13 trials with 974 participants and a median follow-up of 12 months. KA supplementation combined with an LPD or a VLPD significantly increased TSF compared to an LPD alone (SMD, 0.25; 95% CI, 0.04, 0.45; P = 0.02; Fig. 1). No significant differences were observed in serum albumin (SMD, 0.28; 95% CI, -0.05, 0.61; P = 0.10; Fig.) and MAMC (SMD, 0.10; 95% CI, -0.12, 0.32; P = 0.37; Fig. 1). KA supplementation significantly increased serum albumin in patients with a baseline GFR ≥ 20 mL/min/1.73 m² (SMD 0.52; 95% CI, 0.20, 0.84; P = 0.001), but not in those with a baseline GFR < 20 mL/min/1.73 m² (SMD, -0.04; 95% CI, -0.41, 0.34; P = 0.85), and this difference between the subgroups was statistically significant (P = 0.03; Fig. 2). Sensitivity analysis that excluded studies with an in-trial follow-up duration of less than one year yielded results similar to the main analysis, except that the difference in TSF between the intervention and control arms became nonsignificant. Conclusion In patients with stages 3-5 CKD, KA supplementation with a protein-restricted diet did not adversely affect nutritional status. These findings remained consistent in sensitivity analyses of RCTs with a follow-up of more than one year and in subgroup analyses based on baseline GFR. The addition of KAs to protein-restricted diets improved serum albumin levels in patients with a baseline GFR of ≥ 20 mL/min/1.73 m². Our analyses confirmed the efficacy and safety of KA supplementation on nutritional status in advanced CKD patients over a one year follow-up period.