Background Chronic kidney disease (CKD) is associated with a reduced quality of life and an increased risk of kidney failure, cardiovascular events, and all-cause mortality. Accumulation of nitrogen-based uremic toxins leads to worsening of symptoms in individuals with CKD. Many uremic toxins, such as indoxyl and p-cresol sulphate, are produced exclusively by the gut microbiome through the proteolytic digestion of aromatic amino acids. Strategies to reduce the production of these toxins by the gut microbiome in individuals with CKD may lessen symptom burden and delay the onset of dialysis. One such strategy is to change the overall metabolism of the gut microbiome so that less uremic toxins are produced. This can be accomplished by manipulating the energy source available to the microbiome. Fermentable carbohydrates which reach the gut microbiome, like resistant starch (RS), have been shown to inhibit or reduce bacterial amino acid metabolism. This study aims to investigate the effects of resistant potato starch (RPS) as a prebiotic in individuals with CKD before the onset of dialysis. Methods This is a double-blind, randomized two-period crossover trial. Thirty-six eligible participants will consent to follow a 26-week study regimen. Participants will receive 2 sachets per day containing either 15 g of RPS (MSPrebiotic, resistant potato starch treatment) or 15 g cornstarch (Amioca TF, digestible starch control). Changes in blood uremic toxins will be investigated as the primary outcome. Secondary outcomes include the effect of RPS consumption on symptoms, quality of life and abundance, and diversity and functionality of the gut microbiome. Discussion This randomized trial will provide further insight into whether the consumption of RPS as a prebiotic will reduce uremic toxins and symptoms in individuals who have CKD. Trial registration ClinicalTrials.govNCT04961164. Registered on 14 July 2021

Background: Resistant starches (RSs) are not digested by human digestive enzymes and pass through the upper digestive tract to become substrates for colonic bacteria. Resistant starch supplementation has shown promising results in altering the microbiota of animal models of chronic kidney disease (CKD). Resistant starch consumption may influence the production of uremic toxins in CKD. Objective: To conduct a systematic review to determine whether the consumption of RS reduces the progression of kidney disease in adult patients with CKD. Design: We included randomized controlled trials comparing RS supplementation to placebo, no treatment, or standard care. Cochrane Central, Embase, MEDLINE, Web of Science, and CINAHL databases were searched. There was no limitation on publication date, but only English manuscripts were included. The search was conducted in July 2020. Patients: Adult outpatient populations with CKD, using any recognized diagnostic criteria. Measurements: The primary outcome was change in glomerular filtration rate (GFR) from baseline through the end of the trial in patients not on dialysis; secondary outcomes included change in uremic toxin concentrations (p-cresol/p-cresyl sulfate [p-CS], indoxyl sulfate [IS]) and inflammatory markers (tumor necrosis factor alpha [TNF-α], C-reactive protein [CRP], interleukin 6 [IL-6]) from baseline through the end of the trial, and changes in self-reported symptom scores. Methods: The Cochrane Collaboration Risk of Bias tool was used to assess risk of bias in included studies. The systematic review results are reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: We identified 4 unique studies, reported in 9 publications that met our inclusion criteria, including a total of 215 enrolled participants. Results were calculated using data from the longest reported follow-up time. The primary outcome of changes in kidney function markers was only studied in 1 trial; this trial reported an increase in creatinine and a decrease in blood urea nitrogen; no changes in GFR were reported. A review of the secondary outcomes showed an overall decline in IS, TNF-α, and IL-6, in RS groups, but with mixed results in p-CS and CRP/high-sensitivity CRP. Safety data showed that RS was well tolerated with no reports of excessive side effects. Limitations: We determined a meta-analysis was not feasible due to clinical heterogeneity between study populations and differences in reported outcomes in the included studies. Conclusion: There is limited and inconsistent evidence on the impact of RS in adult patients with CKD. Further research is needed to determine the safety and efficacy of RS supplementation in this population.

Background: Chronic kidney disease (CKD) is associated with a reduced quality of life and an increased risk of kidney failure, cardiovascular events, and all-cause mortality. Accumulation of nitrogen-based uremic toxins leads to worsening of symptoms in individuals with CKD. Many uremic toxins, such as indoxyl and p-cresol sulphate, are produced exclusively by the gut microbiome through the proteolytic digestion of aromatic amino acids. Strategies to reduce the production of these toxins by the gut microbiome in individuals with CKD may lessen symptom burden and delay the onset of dialysis. One such strategy is to change the overall metabolism of the gut microbiome so that less uremic toxins are produced. This can be accomplished by manipulating the energy source available to the microbiome. Fermentable carbohydrates which reach the gut microbiome, like resistant starch (RS), have been shown to inhibit or reduce bacterial amino acid metabolism. This study aims to investigate the the effects of resistant potato starch (RPS) as a prebiotic in individuals with CKD before the onset of dialysis. Methods: This is a double blind, randomized two-period crossover trial. 36 eligible participants will consent to follow a 26-week study regimen. Participants will receive 2 sachets per day containing either 15 grams of RPS (MSPrebiotic, resistant potato starch treatment) or 15 grams corn starch (Amioca TF, digestible starch control). Changes in blood uremic toxins will be investigated as the primary outcome. Secondary outcomes include the effect of RPS consumption on symptoms, quality of life and the abundance, diversity and functionality of the gut microbiome.Discussion: This pilot randomized trial will provide further insight into whether the consumption of RPS as a prebiotic will reduce uremic toxins and symptoms in individuals who have CKD. Trial registration: NCT04961164

Background: Dietary modifications represent an important intervention to reduce the risk of chronic disease. Appropriate dietary changes can be simple to implement and are usually suggested as first line recommendations for many types of chronic disease management including diseases like hypertension and diabetes. Resistant starch is a non-digestible carbohydrate which passes through untouched to the colon where it becomes a digestible substrate for beneficial colonic bacteria. The normal gut flora becomes damaged in patients with chronic kidney disease with an additional buildup of uremic toxins and resulting intra-renal inflammation. Resistant starch supplementation has been studied for its effects on reducing harmful metabolite buildup through a restoration of normal gut flora. The following systematic review aims to compile the evidence of resistant starch use in adult patients with chronic kidney disease to answer whether or not the dietary intervention can reduce the progression of renal disease. Methods: We will perform a literature search with a knowledge synthesis librarian including the following databases: MEDLINE, Cochrane Central, Embase, CINAHL, and Web of Science. Collected data will be extracted and organized in MS Excel 2019. The extraction of the data will include study details, study population details, intervention details, and outcome details.Discussion: Results from this systematic review may help to determine a simple and effective method for prolonging the need for renal replacement therapy through resistant starch supplementation. Lack of evidence may highlight the need for additional trials or new interventions. PROSPERO ID: Currently being assessed, ID: 203138.