#761 Effect of ketoanalogue-supplemented very low protein diet in the need to initiate renal replacement in chronic kidney disease patients

Abstract Background and Aims Chronic kidney disease (CKD) is a global concern, with increasing complications and potential end-stage renal disease. Protein intake restriction is crucial for conservative therapy. Investigators have theorized on the nephroprotective effect of either a very low-protein diet (VLPD) with ketoanalogues (KAA) or a low-protein diet (LPD); this was however not confirmed by the Modification of Diet in Renal Disease (MDRD) randomized clinical trial (RCT). This meta-analysis aims to evaluate the effect of VLPD supplemented with KAA on RRT need and disease progression among CKD patients. Method A systematic literature search was conducted up to January 3, 2024 for trials in the following databases: PUBMED/MEDLINE, Ovid MEDLINE, Google Scholar, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science and ClincalTrials.gov. Studies that compared VLPD supplemented with KAA to LPD in pre-dialysis CKD patients demonstrating outcomes such as the need for RRT, CKD progression, and all-cause mortality were included. A total of four studies were included in the final analysis. The number of individuals requiring and not requiring RRT on follow-up were computed and analyzed using fixed effects model; while CKD progression and mortality were analyzed using random effects models. Results Four studies (738 participants) investigated patients who needed RRT, CKD progression, and all-cause mortality on follow-up between those on VLPD with KAA and LPD. In Fig. 1, VLPD with KAA reduced the need of RRT by 36% (Odds Ratio 0.64, 95% CI: 0.45 to 0.93, P = 0.02), and decreased the incidence of CKD progression (Fig. 2) by 65% (Odds Ratio 0.35, 95% CI: 0.14 to 0.87, P = 0.02). Three studies (531 participants) reported on all-cause mortality (Fig. 3), and our analysis did not show a significant effect on all-cause mortality (OR 1.46, 95% CI: 0.72 to 2.96, P = 0.29). There was no significant heterogeneity among the studies. Conclusion The investigators conclude that the present meta-analysis of 4 RCTs demonstrates that the use of VLPD supplemented with KAA reduced the need for RRT initiation and progression of CKD among pre-dialysis CKD Stage 4-5 patients when compared to those on the conventional LPD regimen. Therefore, protein restriction diets especially VLPD with KAA should be considered and offered in eligible CKD patients as part of their supportive management.