Effects of a Metabolic Mixture on Gut Inflammation and Permeability in Elderly Patients with Chronic Kidney Disease: A Proof-of-Concept Study

Abstract

Intestinal barrier dysfunction is a risk factor for the progression of Chronic Kidney Disease (CKD). In this proof-of-concept study, we tested the effects of a mixture of Essential Amino Acids (EAAs) and mitochondrial substrates on intestinal inflammation and permeability of CKD patients. Eight patients with stage 3b-4 CKD and 11 healthy controls after overnight fasting underwent fecal measures of calprotectin and zonulin levels (indicators of gut inflammation and permeability, respectively) and determinations of plasma amino acids. Only CKD patients were supplemented with the mixture (8 g/d diluted in water). Compared to controls, baseline fecal calprotectin, zonulin and plasma levels of some AA in CKD patients were significantly higher (p = 0.005; p = 0.001 and p = 0.02 to 0.003, respectively). After six months of supplementation, CKD baseline fecal levels of calprotectin and zonulin significantly (borderline for zonulin) decreased (p = 0.008 and p = 0.05, respectively). Plasma AA concentrations, including glutamine and alanine, were higher than at the baseline (p: 0.05 to 0.008). The supplementation of this mixture was associated with improved intestinal barrier dysfunction. Increased plasma AA levels might contribute to the improvement of gut barrier dysfunction.

Keywords: chronic kidney disease; gut inflammation and permeability; mitochondrial intermediates.

Figure 1

Scatterplot showing the association between baseline fecal Calprotectin and Zonulin. Spearman’s r and Pearson’s r are also reported. The red dash-dotted line represents the linear fit.

Figure 2

Some potential mechanisms underlying EAA-associated improved intestinal barrier dysfunction in the study CKD.