SP400VERY LOW PROTEIN DIET REDUCES SERUM LEVELS OF INDOXYL SULFATE AND P-CRESYL SULFATE IN CHRONIC KIDNEY DISEASE

Abstract

INTRODUCTION AND AIMS: High serum levels of uremic nephrovascular toxins, indoxyl sulfate (IS) and p‐cresyl sulfate (PCS), are associated with chronic kidney disease (CKD) progression and increased risk of cardiovascular disease and mortality in CKD patients. IS and PCS cannot be efficiently removed by conventional haemodialysis, due to their high binding affinity for albumin. The aim of this pilot study was to assess whether a Mediterranean Diet (MD) and a Very Low Protein Diet supplemented with amino acids and ketoacids (s‐VLPD) would reduce serum concentrations of IS and PCS in CKD patients. METHODS: This is a prospective randomized cross‐over controlled trial enrolling 60 CKD grade 3B‐4 patients, divided into two arms of 30 patients, which alternatively underwent 3 dietary schemes as follows: 3 months free diet (FD: proteins 1 gram/body weight/day), 6 months s‐VLPD (proteins 0.3‐0.5 gram/body weight/day + 0.05 gram/ body weight/day ketoacids supplementation), 3 months FD, 6 months MD (proteins 0.7‐0.8 gram/body weight/day); and 3 months FD, 6 months MD, 3 months FD, 6 months s‐VLPD. Total and free IS and PCS were quantitatively and simultaneously measured, at baseline and at the end of each dietary scheme, by liquid chromatography/ electrospray ionization‐tandem mass spectrometry (LC/ESI‐MS/MS). Differences between IS and PCS serum levels were tested by Wilcoxon test. RESULTS: Preliminary data on 30 out of 60 CKD patients show that s‐VLPD diet is very effective in reducing total IS (3.05±0.76 μg/mL, p=0.003) and PCS (12.5±2.7 μg/ mL, p=0.02) serum levels compared to FD (IS: 12.84±2.83 μg/mL; PCS: 23.3±3.5 μg/ mL). MD reduces serum levels of total IS (6.72±2.2 μg/mL, p=0.08) and PCS (14.06±2.9 μg/mL, p=0.04) compared to FD, showing the same trend of s‐VLPD, although the decrease of IS serum levels remains not statistically significant. CONCLUSIONS: The preliminary results of this pilot study show for the first time, to the best of our knowledge, that both, MD and, to a greater extent s‐VLPD, are effective in reducing serum levels of microbiota‐generated uremic toxins, specifically IS and PCS, in CKD patients.