Effect of a Very-Low-Protein Diet Supplemented with Ketoacid Analogues on Arteriovenous Fistula Maturation and Endothelial Function: A Prospective Observational Study.
Barbarini S, Protopapa P, et al. • Nutrients • 2026
VLPD+KA therapy enhances vascular integrity, reduces uremic endotheliotoxicity, and facilitates successful AVF maturation, achieving 95% maturation rate with zero CVC dependency among patients who initiated dialysis.
Key Findings
Results
A very-low-protein diet supplemented with ketoacid analogues (VLPD+KA) significantly improved endothelial function as measured by flow-mediated dilation (FMD).
FMD increased by +1.7% (p < 0.01) over the three-month follow-up period.
Endothelial function was assessed via flow-mediated dilation (FMD) using vascular imaging metrics.
The study enrolled 20 patients with advanced CKD (stage V) scheduled for AVF creation.
The VLPD protocol required 0.3–0.4 g/kg/day protein with KA supplementation at 1 tablet/5 kg/day.
Results
VLPD+KA supplementation produced substantial reductions in uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS).
Indoxyl sulfate (IS) was reduced by 38% (p < 0.001).
p-Cresyl sulfate (PCS) was reduced by 43% (p < 0.001).
Both IS and PCS are known uremic endotheliotoxins implicated in vascular dysfunction in CKD.
Reductions were observed over a three-month follow-up period in 20 CKD stage V patients.
Results
CRP levels were markedly decreased following VLPD+KA intervention, indicating reduced systemic inflammation.
CRP decreased from 3.2 mg/L to 1.1 mg/L (p < 0.01).
Inflammatory markers assessed included both CRP and ESR.
The reduction in CRP was observed over the three-month study period.
Reduced inflammation may contribute to improved endothelial function and AVF maturation outcomes.
Results
AVF maturation was achieved in 95% of patients following the VLPD+KA intervention.
95% of the 20 enrolled CKD stage V patients achieved successful AVF maturation.
Zero patients who initiated dialysis had central venous catheter (CVC) dependency.
AVF maturation, CVC requirement, and dialysis initiation timing were monitored over a three-month follow-up.
Kaplan-Meier analysis was used for time-to-event endpoints including dialysis initiation.
Results
Nutritional status remained stable throughout the VLPD+KA intervention period, confirming metabolic safety of the regimen.
Nutritional status was assessed by BMI, BIA-derived phase angle, and handgrip strength.
All three nutritional indicators remained stable over the three-month follow-up period.
The VLPD protocol was strict at 0.3–0.4 g/kg/day protein, which is well below standard low-protein recommendations.
Stability of nutritional markers confirmed that the regimen did not lead to protein-energy wasting.
Methods
The study design was a prospective observational study of 20 advanced CKD patients using within-group statistical comparisons.
20 patients with CKD stage V scheduled for AVF creation were enrolled.
Statistical analyses included paired t-tests or Wilcoxon signed-rank tests for within-group comparisons.
Fisher's exact test was used for categorical variables and Kaplan-Meier analysis for time-to-event endpoints.
Analyses were performed using SPSS version 27.0.
The study had no control group, as it was observational in design, and the authors note that larger randomized controlled trials are warranted.
Background
Endothelial dysfunction and arterial stiffness prevalent in advanced CKD were identified as key impediments to AVF maturation.
Endothelial dysfunction and arterial stiffness are described as 'highly prevalent in advanced chronic kidney disease (CKD)' and 'frequently impair AVF maturation.'
AVF maturation is described as 'a critical determinant for successful hemodialysis in patients with end-stage renal disease (ESRD).'
Uremic toxins such as IS and PCS contribute to endothelial damage, framed as 'uremic endotheliotoxicity.'
The study positioned VLPD+KA as a means to mitigate nitrogenous waste accumulation and improve vascular health by reducing inflammation.
What This Means
This research suggests that a very strict low-protein diet (about one-third of the typical recommended protein intake) combined with special amino acid supplements called ketoacid analogues can meaningfully improve blood vessel health in patients with advanced kidney disease who are preparing for dialysis. In a group of 20 such patients, following this dietary regimen for three months led to better blood vessel flexibility (as measured by a technique called flow-mediated dilation), lower levels of toxic waste products that build up when the kidneys fail, and reduced markers of inflammation in the blood — all without causing any loss of muscle or nutritional status.
One of the most striking findings was that 95% of patients successfully developed a working arteriovenous fistula (AVF) — a surgically created connection between an artery and vein in the arm that is essential for hemodialysis — and none of the patients who started dialysis needed a temporary central venous catheter, which carries significant infection risks. This is notable because poor blood vessel health in kidney disease often causes AVF failure, forcing patients to rely on these riskier catheter alternatives.
This research suggests that dietary management before dialysis begins could play an important role in preparing the body's blood vessels for the demands of hemodialysis access. However, this was a small observational study without a control group for comparison, so the authors emphasize that larger randomized controlled trials are needed before this approach could be considered a standard part of pre-dialysis care.
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Barbarini S, Protopapa P, Fontò G, Ria P, Pesino A, Zito A, et al.. (2026). Effect of a Very-Low-Protein Diet Supplemented with Ketoacid Analogues on Arteriovenous Fistula Maturation and Endothelial Function: A Prospective Observational Study.. Nutrients. https://doi.org/10.3390/nu18111777