Effect of a Very-Low-Protein Diet Supplemented with Ketoacid Analogues on Arteriovenous Fistula Maturation and Endothelial Function: A Prospective Observational Study

Background: Arteriovenous fistula (AVF) maturation is a critical determinant for successful hemodialysis in patients with end-stage renal disease (ESRD). Endothelial dysfunction and arterial stiffness, which are highly prevalent in advanced chronic kidney disease (CKD), frequently impair AVF maturation. Emerging evidence suggests that a very-low-protein diet (VLPD) supplemented with ketoacid analogues (KA) mitigates nitrogenous waste accumulation and positively influences vascular health by reducing inflammation and improving endothelial function. This prospective observational study evaluates the effect of VLPD+KA on AVF maturation, endothelial function, inflammatory markers, nutritional status, and the timing of dialysis initiation. We enrolled 20 patients with advanced CKD (stage V) scheduled for AVF creation. Participants adhered to a strict VLPD protocol (0.3–0.4 g/kg/day) with KA supplementation (1 tablet/5 kg/day). We assessed biochemical parameters, inflammatory markers (CRP, ESR), uremic toxins (indoxyl sulfate [IS], p-cresyl sulfate [PCS]), endothelial function via flow-mediated dilation (FMD), and vascular imaging metrics. AVF maturation, central venous catheter (CVC) requirement, dialysis initiation, and nutritional parameters were monitored over a three-month follow-up period. Statistical analyses included paired t-tests or Wilcoxon signed-rank tests for within-group comparisons, Fisher’s exact test for categorical variables, and Kaplan–Meier analysis for time-to-event endpoints, performed using SPSS version 27.0. Results: The intervention led to significant improvements in endothelial function (FMD +1.7%, p < 0.01), substantial reductions in the uremic toxins IS (−38%, p < 0.001) and PCS (−43%, p < 0.001), and a marked decrease in CRP levels (from 3.2 to 1.1 mg/L, p < 0.01). Nutritional status, assessed by BMI, BIA-derived phase angle, and handgrip strength, remained stable throughout the intervention period, confirming the metabolic safety of the VLPD+KA regimen. Notably, AVF maturation was achieved in 95% of patients, with zero CVC dependency among those who initiated dialysis. Conclusions: These findings strongly support the hypothesis that VLPD+KA therapy enhances vascular integrity, reduces uremic endotheliotoxicity, and facilitates successful AVF maturation. This nutritional intervention warrants further investigation in larger, randomized controlled trials as a standard pre-dialysis care strategy.