Abstract
In chronic kidney disease (CKD), the gut-microbiota metabolites indoxyl sulfate (IS) and p-cresyl sulfate (PCS) progressively accumulate due to their high albumin-binding capacity, leading to clinical complications. In a prospective crossover controlled trial, 60 patients with CKD grades 3B–4 (GFR = 21.6 ± 13.2 mL/min) were randomly assigned to two dietary regimens: (i) 3 months of free diet (FD) (FD is the diet usually used by the patient before being enrolled in the Medika study), 6 months of very low protein diet (VLPD), 3 months of FD and 6 months of Mediterranean diet (MD); (ii) 3 months of FD, 6 months of MD, 3 months of FD, and 6 months of VLPD. VLPD reduced inflammatory Proteobacteria and increased Actinobacteria phyla. MD and VLPD increased some butyrate-forming species of Lachnospiraceae, Ruminococcaceae, Prevotellaceae, Bifidobacteriaceae, and decrease the pathobionts Enterobacteriaceae. The increased level of potential anti-inflammatory Blautia and Faecalibacterium, as well as butyrate-forming Coprococcus and Roseburia species in VLPD was positively associated with dietary intakes and it was negatively correlated with IS and PCS. Compared to FD and MD, VLPD showed a lower amount of some Lactobacillus, Akkermansia, Streptococcus, and Escherichia species. MD and VLPD reduced both the total and free serum IS (MD −36%, −40% and VLPD −69%, −73%, respectively) and PCS (MD −38%, −44% and VLPD −58%, −71%, respectively) compared to FD. VLPD reduced serum D-lactate compared to MD and FD. MD and, to a greater extent, VLPD are effective in the beneficial modulation of gut microbiota, reducing IS and PCS serum levels, and restoring intestinal permeability in CKD patients.
Highlights
Over time, nutritional therapy (NT) has become a cornerstone of the conservative treatment of chronic kidney disease (CKD), aiming basically to administrate a reduced amount of high biological value proteins to reduce the urea production in patients with CKD [1,2]
Due to the high binding affinity of indoxyl sulfate (IS) and p-cresyl sulfate (PCS) to albumin, they cannot be efficiently removed by conventional hemodialysis and progressively accumulate in CKD patients leading to disease progression and resulting in organ damage [18]
Medika is the first known study evaluating the effects of Mediterranean diet (MD) and very low protein diet (VLPD) on the modulation of intestinal microbiota and, on the variation of serum IS and PCS levels in patients with CKD
Summary
Nutritional therapy (NT) has become a cornerstone of the conservative treatment of chronic kidney disease (CKD), aiming basically to administrate a reduced amount of high biological value proteins to reduce the urea production in patients with CKD [1,2]. As CKD progresses, a lower protein intake becomes increasingly necessary, up to regimens that include a vegan diet [13,14] or a very low protein diet (VLPD) supplemented with essential amino acids and ketoacids [15,16]. The latter are capable of inducing a massive reduction of urea to levels that may be deemed comparable to healthy subjects [10]. Strategies aimed at lowering their intestinal production are desirable
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