Diet Quality and Protein-Bound Uraemic Toxins: Investigation of Novel Risk Factors and the Role of Microbiome in Chronic Kidney Disease.

OBJECTIVE: This study aims to explore the associations between diet quality, uraemic toxins, and gastrointestinal microbiota in the chronic kidney disease (CKD) population. METHODS: This is a baseline cross-sectional study of adults with CKD participating in a randomized controlled trial of prebiotic and probiotic supplementation. Dietary intake was measured using a seven-day diet history method, administered by a specialist dietitian. Diet quality was assessed using plant-based diet index (PDI) (overall PDI, healthy PDI, and unhealthy PDI), food group analysis, protein intake, fiber intake, and dietary protein-to-fiber ratio. Serum uraemic toxins (free and total; indoxyl sulfate and p-cresyl sulfate) were determined by ultraperformance liquid chromatography. Gastrointestinal microbiota richness, diversity, composition, and functional capacity were analyzed via metagenomic sequencing. RESULTS: Sixty-eight adults [median age: 70 (interquartile range: 58-75) years, 66% male] with an estimated glomerular filtration rate of 34 ± 11 mL/min/1.73 m2 were included, with 40 participants completing the optional fecal substudy. Dietary fiber intake was associated with lower levels of total indoxyl sulfate, whereas the healthy plant-based diet index was associated with lower levels of free p-cresyl sulfate. A higher protein-to-fiber ratio was associated with an increased relative abundance of unclassified members of order Oscillospirales. Intake of vegetables and whole grains was correlated with Subdoligranulum formicile, whereas an unclassified Prevotella species was correlated with potatoes and food items considered discretionary, including sweet drinks, sweet desserts, and animal fats. CONCLUSIONS: Diet quality may influence uraemic toxin generation and gut microbiota diversity, composition, and function in adults with CKD. Well-designed dietary intervention studies targeting the production of uraemic toxins and exploring the impact on gut microbiome are warranted in the CKD population.

A Renal Clinician's Guide to the Gut Microbiota.

It is increasingly recognized that the gut microbiota plays a role in the progression of chronic diseases and that diet may confer health benefits by altering the gut microbiota composition. This is of particular relevance for chronic kidney disease (CKD), as the gut is a source of uremic retention solutes, which accumulate as a result of impaired kidney function and can exert nephrotoxic and other harmful effects. Kidney dysfunction is also associated with changes in the composition of the gut microbiota and the gastrointestinal tract. Diet modulates the gut microbiota, and there is much interest in the use of prebiotics, probiotics, and synbiotics as dietary therapies in CKD, as well as dietary patterns that beneficially alter the microbiota. This review provides an overview of the gut microbiota and its measurement, its relevance in the context of CKD, and the current state of knowledge regarding dietary manipulation of the microbiota.

Metabolic Effects of Resistant Starch Type 2: A Systematic Literature Review and Meta-Analysis of Randomized Controlled Trials.

Published evidence exploring the effects of dietary resistant starch (RS) on human cardiometabolic health is inconsistent. This review aimed to investigate the effect of dietary RS type 2 (RS2) supplementation on body weight, satiety ratings, fasting plasma glucose, glycated hemoglobin (HbA1c), insulin resistance and lipid levels in healthy individuals and those with overweight/obesity, the metabolic syndrome (MetS), prediabetes or type 2 diabetes mellitus (T2DM). Five electronic databases were searched for randomized controlled trials (RCTs) published in English between 1982 and 2018, with trials eligible for inclusion if they reported RCTs involving humans where at least one group consumed ≥ 8 g of RS2 per day and measured body weight, satiety, glucose and/or lipid metabolic outcomes. Twenty-two RCTs involving 670 participants were included. Meta-analyses indicated that RS2 supplementation significantly reduced serum triacylglycerol concentrations (mean difference (MD) = -0.10 mmol/L; 95% CI -0.19, -0.01, P = 0.03) in healthy individuals (n = 269) and reduced body weight (MD = -1.29 kg; 95% CI -2.40, -0.17, P = 0.02) in people with T2DM (n = 90). However, these outcomes were heavily influenced by positive results from a small number of individual studies which contradicted the conclusions of the majority of trials. RS2 had no effects on any other metabolic outcomes. All studies ranged from 1-12 weeks in duration and contained small sample sizes (10-60 participants), and most had an unclear risk of bias. Short-term RS2 supplementation in humans is of limited cardiometabolic benefit.

Modulation of the Gut Microbiota by Resistant Starch as a Treatment of Chronic Kidney Diseases: Evidence of Efficacy and Mechanistic Insights.

Chronic kidney disease (CKD) has been associated with changes in gut microbial ecology, or "dysbiosis," which may contribute to disease progression. Recent studies have focused on dietary approaches to favorably alter the composition of the gut microbial communities as a treatment method in CKD. Resistant starch (RS), a prebiotic that promotes proliferation of gut bacteria such as Bifidobacteria and Lactobacilli, increases the production of metabolites including short-chain fatty acids, which confer a number of health-promoting benefits. However, there is a lack of mechanistic insight into how these metabolites can positively influence renal health. Emerging evidence shows that microbiota-derived metabolites can regulate the incretin axis and mitigate inflammation via expansion of regulatory T cells. Studies from animal models and patients with CKD show that RS supplementation attenuates the concentrations of uremic retention solutes, including indoxyl sulfate and p-cresyl sulfate. Here, we present the current state of knowledge linking the microbiome to CKD, we explore the efficacy of RS in animal models of CKD and in humans with the condition, and we discuss how RS supplementation could be a promising dietary approach for slowing CKD progression.

Stirring the Pot: Can Dietary Modification Alleviate the Burden of CKD?

Diet is one of the largest modifiable risk factors for chronic kidney disease (CKD)-related death and disability. CKD is largely a progressive disease; however, it is increasingly appreciated that hallmarks of chronic kidney disease such as albuminuria can regress over time. The factors driving albuminuria resolution remain elusive. Since albuminuria is a strong risk factor for GFR loss, modifiable lifestyle factors that lead to an improvement in albuminuria would likely reduce the burden of CKD in high-risk individuals, such as patients with diabetes. Dietary therapy such as protein and sodium restriction has historically been used in the management of CKD. Evidence is emerging to indicate that other nutrients may influence kidney health, either through metabolic or haemodynamic pathways or via the modification of gut homeostasis. This review focuses on the role of diet in the pathogenesis and progression of CKD and discusses the latest findings related to the mechanisms of diet-induced kidney disease. It is possible that optimizing diet quality or restricting dietary intake could be harnessed as an adjunct therapy for CKD prevention or progression in susceptible individuals, thereby reducing the burden of CKD.