Consumers' Perspectives and Experiences of Prebiotics and Probiotics for Gut Health in Chronic Kidney Disease.

OBJECTIVES: Nutrition supplementation, including prebiotics and probiotics, is a therapeutic strategy for modulating the gut microbiome in chronic kidney disease (CKD). However, the acceptability of gut-targeted supplements in this population remains largely unexplored. This study aims to describe the perceptions of nutrition supplementation, and the acceptability and experiences of pre- and probiotics in adults with Stage 3-4 CKD. DESIGN AND METHODS: Semi-structured interview study of adults with Stage 3-4 CKD (n = 30), aged 41-80 (mean 68) years, who completed a 12-month prebiotic and probiotic intervention or placebo, were interviewed between January and March 2019. Interviews were transcribed verbatim and analyzed thematically. RESULTS: Five themes were identified: integrating and sustaining routine supplementation (flexibility in prescription of prebiotics and probiotics, fitting in with regular routines); striving for health benefits (hoping to improve kidney health, hoping to improve general health, confirming health benefits); facilitating pre- and probiotic supplementation (perceiving pre- and probiotics as safe, side-effects from taking pre- and probiotics); empowering knowledge (valuing the opportunity to increase knowledge of gut health); and considerations for future use (questioning credibility of health claims, average palatability of prebiotic powder, cost concerns). CONCLUSIONS: Adults with Stage 3-4 CKD found pre- and probiotic supplements to be acceptable and complementary gut-targeted supplements. Individual preferences for nutrition supplementation should be considered alongside health knowledge to enhance uptake and adherence in practice.

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.

Synbiotics Easing Renal Failure by Improving Gut Microbiology II (SYNERGY II): A Feasibility Randomized Controlled Trial.

Synbiotics have emerged as a therapeutic strategy for modulating the gut microbiome and targeting novel cardiovascular risk factors, including uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS). This study aims to evaluate the feasibility of a trial of long-term synbiotic supplementation in adults with stage 3-4 chronic kidney disease (CKD). Adult participants with CKD and estimated glomerular filtration rate (eGFR) of 15-60 mL/min/1.73 m2) were recruited between April 2017 and August 2018 to a feasibility, double-blind, placebo-controlled, randomized trial of synbiotic therapy or matched identical placebo for 12 months. The primary outcomes were recruitment and retention rates as well as acceptability of the intervention. Secondary outcomes were treatment adherence and dietary intake. Exploratory outcomes were evaluation of the cardiovascular structure and function, serum IS and PCS, stool microbiota profile, kidney function, blood pressure, and lipid profile. Of 166 potentially eligible patients, 68 (41%) were recruited into the trial (synbiotic n = 35, placebo n = 33). Synbiotic and placebo groups had acceptable and comparable 12-month retention rates (80% versus 85%, respectively, p = 0.60). Synbiotic supplementation altered the stool microbiome with an enrichment of Bifidobacterium and Blautia spp., resulting in a 3.14 mL/min/1.73 m2 (95% confidence interval (CI), -6.23 to -0.06 mL/min/1.73 m2, p < 0.01) reduction in eGFR and a 20.8 µmol/L (95% CI, 2.97 to 38.5 µmol/L, p < 0.01) increase in serum creatinine concentration. No between-group differences were observed in any of the other secondary or exploratory outcomes. Long-term synbiotic supplementation was feasible and acceptable to patients with CKD, and it modified the gastrointestinal microbiome. However, the reduction in kidney function with synbiotics warrants further investigation.

The Impact of Systematic Review Automation Tools on Methodological Quality and Time Taken to Complete Systematic Review Tasks: Case Study.

BACKGROUND: Systematic reviews (SRs) are considered the highest level of evidence to answer research questions; however, they are time and resource intensive. OBJECTIVE: When comparing SR tasks done manually, using standard methods, versus those same SR tasks done using automated tools, (1) what is the difference in time to complete the SR task and (2) what is the impact on the error rate of the SR task? METHODS: A case study compared specific tasks done during the conduct of an SR on prebiotic, probiotic, and synbiotic supplementation in chronic kidney disease. Two participants (manual team) conducted the SR using current methods, comprising a total of 16 tasks. Another two participants (automation team) conducted the tasks where a systematic review automation (SRA) tool was available, comprising of a total of six tasks. The time taken and error rate of the six tasks that were completed by both teams were compared. RESULTS: The approximate time for the manual team to produce a draft of the background, methods, and results sections of the SR was 126 hours. For the six tasks in which times were compared, the manual team spent 2493 minutes (42 hours) on the tasks, compared to 708 minutes (12 hours) spent by the automation team. The manual team had a higher error rate in two of the six tasks-regarding Task 5: Run the systematic search, the manual team made eight errors versus three errors made by the automation team; regarding Task 12: Assess the risk of bias, 25 assessments differed from a reference standard for the manual team compared to 20 differences for the automation team. The manual team had a lower error rate in one of the six tasks-regarding Task 6: Deduplicate search results, the manual team removed one unique study and missed zero duplicates versus the automation team who removed two unique studies and missed seven duplicates. Error rates were similar for the two remaining compared tasks-regarding Task 7: Screen the titles and abstracts and Task 9: Screen the full text, zero relevant studies were excluded by both teams. One task could not be compared between groups-Task 8: Find the full text. CONCLUSIONS: For the majority of SR tasks where an SRA tool was used, the time required to complete that task was reduced for novice researchers while methodological quality was maintained.

Interventions for weight loss in people with chronic kidney disease who are overweight or obese.

BACKGROUND: Obesity and chronic kidney disease (CKD) are highly prevalent worldwide and result in substantial health care costs. Obesity is a predictor of incident CKD and progression to kidney failure. Whether weight loss interventions are safe and effective to impact on disease progression and clinical outcomes, such as death remains unclear. OBJECTIVES: This review aimed to evaluate the safety and efficacy of intentional weight loss interventions in overweight and obese adults with CKD; including those with end-stage kidney disease (ESKD) being treated with dialysis, kidney transplantation, or supportive care. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 14 December 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of more than four weeks duration, reporting on intentional weight loss interventions, in individuals with any stage of CKD, designed to promote weight loss as one of their primary stated goals, in any health care setting. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and extracted data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess the certainty of evidence. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised mean difference (SMD) for continuous outcomes or in descriptive format when meta-analysis was not possible. MAIN RESULTS: We included 17 RCTs enrolling 988 overweight or obese adults with CKD. The weight loss interventions and comparators across studies varied. We categorised comparisons into three groups: any weight loss intervention versus usual care or control; any weight loss intervention versus dietary intervention; and surgical intervention versus non-surgical intervention. Methodological quality was varied, with many studies providing insufficient information to accurately judge the risk of bias. Death (any cause), cardiovascular events, successful kidney transplantation, nutritional status, cost effectiveness and economic analysis were not measured in any of the included studies. Across all 17 studies many clinical parameters, patient-centred outcomes, and adverse events were not measured limiting comparisons for these outcomes. In studies comparing any weight loss intervention to usual care or control, weight loss interventions may lead to weight loss or reduction in body weight post intervention (6 studies, 180 participants: MD -3.69 kg, 95% CI -5.82 to -1.57; follow-up: 5 weeks to 12 months, very low-certainty evidence). In very low certainty evidence any weight loss intervention had uncertain effects on body mass index (BMI) (4 studies, 100 participants: MD -2.18 kg/m², 95% CI -4.90 to 0.54), waist circumference (2 studies, 53 participants: MD 0.68 cm, 95% CI -7.6 to 6.24), proteinuria (4 studies, 84 participants: 0.29 g/day, 95% CI -0.76 to 0.18), systolic (4 studies, 139 participants: -3.45 mmHg, 95% CI -9.99 to 3.09) and diastolic blood pressure (4 studies, 139 participants: -2.02 mmHg, 95% CI -3.79 to 0.24). Any weight loss intervention made little or no difference to total cholesterol, high density lipoprotein cholesterol, and inflammation, but may lower low density lipoprotein cholesterol. There was little or no difference between any weight loss interventions (lifestyle or pharmacological) compared to dietary-only weight loss interventions for weight loss, BMI, waist circumference, proteinuria, and systolic blood pressure, however diastolic blood pressure was probably reduced. Furthermore, studies comparing the efficacy of different types of dietary interventions failed to find a specific dietary intervention to be superior for weight loss or a reduction in BMI. Surgical interventions probably reduced body weight (1 study, 11 participants: MD -29.50 kg, 95% CI -36.4 to -23.35), BMI (2 studies, 17 participants: MD -10.43 kg/m², 95% CI -13.58 to -7.29), and waist circumference (MD -30.00 cm, 95% CI -39.93 to -20.07) when compared to non-surgical weight loss interventions after 12 months of follow-up. Proteinuria and blood pressure were not reported. All results across all comparators should be interpreted with caution due to the small number of studies, very low quality of evidence and heterogeneity across interventions and comparators. AUTHORS' CONCLUSIONS: All types of weight loss interventions had uncertain effects on death and cardiovascular events among overweight and obese adults with CKD as no studies reported these outcome measures. Non-surgical weight loss interventions (predominately lifestyle) appear to be an effective treatment to reduce body weight, and LDL cholesterol. Surgical interventions probably reduce body weight, waist circumference, and fat mass. The current evidence is limited by the small number of included studies, as well as the significant heterogeneity and a high risk of bias in most studies.

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.

Prebiotic, Probiotic, and Synbiotic Supplementation in Chronic Kidney Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: Gut dysbiosis has been implicated in the pathogenesis of chronic kidney disease (CKD). Restoring gut microbiota with prebiotic, probiotic, and synbiotic supplementation has emerged as a potential therapeutic intervention but has not been systematically evaluated in the CKD population. DESIGN AND METHODS: This is a systematic review. A structured search of MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and the International Clinical Trials Register Search Portal was conducted for articles published since inception until July 2017. Included studies were randomized controlled trials investigating the effects of prebiotic, probiotic, and/or synbiotic supplementation (>1 week) on uremic toxins, microbiota profile, and clinical and patient-centered outcomes in adults and children with CKD. RESULTS: Sixteen studies investigating 645 adults met the inclusion criteria; 5 investigated prebiotics, 6 probiotics, and 5 synbiotics. The quality of the studies (Grades of Recommendation, Assessment, Development and Evaluation) ranged from moderate to very low. Prebiotic, probiotic, and synbiotic supplementation may have led to little or no difference in serum urea (9 studies, 345 participants: mean difference [MD] -0.30 mmol/L, 95% confidence interval [CI] -2.20 to 1.61, P = .76, I2 = 53%), indoxyl sulfate (4 studies, 144 participants: MD -0.02 mg/dL, 95% CI -0.09 to 0.05, P = .61, I2 = 0%), and p-cresyl sulfate (4 studies, 144 participants: MD -0.13 mg/dL, 95% CI -0.41 to 0.15, P = .35, I2 = 0%). Prebiotic supplementation may have slightly reduced serum urea concentration (4 studies, 105 participants: MD -2.23 mmol/L, 95% CI -3.83 to -0.64, P = .006, I2 = 11). Of the 2 studies investigating microbiota changes, synbiotic interventions significantly increased Bifidobacterium. Supplement effects on clinical outcomes were uncertain. CONCLUSIONS: There is limited evidence to support the use of prebiotics, probiotics, and/or synbiotics in CKD management.

Implementation of standardized nutrition guidelines by renal dietitians is associated with improved nutrition status.

OBJECTIVE: Standardized nutrition guidelines that focus on a nutrition care process have been used by dietitians treating renal patients in Australia for over 3 years. We show the impact of this implementation on the nutritional status of a cohort of hemodialysis patients. DESIGN: We conducted a retrospective observational study, investigating a cohort of maintenance hemodialysis patients after the implementation of a systematic approach to the patient's nutritional care. SETTING: This study took place in public and private in-center hemodialysis units. PATIENTS: Patients included a cohort of 65 maintenance hemodialysis patients (mean age +/- SD, 64 +/- 15 years; 58% male; dialysis vintage median [interquartile range], 22 [10 to 46] months). INTERVENTIONS: All participants were provided with a dietary interview at least every 6 months, with intensive follow-up where required, and were monitored monthly regarding weight and biochemistry. Outcomes were assessed annually between May 2004 and December 2006, after the implementation of this model of care. MAIN OUTCOME MEASURE: Energy and protein intake according to dietary interview, nutritional status according to subjective global assessment, and data regarding dry weight and biochemistry (including albumin, potassium, and phosphate) were collected by the dietitian at each facility. Change in each outcome measure over time was assessed using repeated-measures analysis. RESULTS: The proportion of patients with malnutrition (subjective global assessment B or C) decreased from 14% at baseline to 3% after 2 years. Serum albumin, potassium, and dry weight remained stable throughout the study period, and there was a significant decrease in serum phosphate over time (mean +/- SD,1.8 +/- 0.5 to 1.5 +/- 0.5 mmol/L, P = .004). Dietary energy and protein intake changed significantly over the study period (P = .001 and P = .022, respectively), with the highest mean intake recorded during the final follow-up assessment. CONCLUSIONS: The implementation of a systematic approach to patient care, in line with nutrition management guideline recommendations, was associated with an improvement in nutritional status and dietary intake in this cohort of maintenance hemodialysis patients, without the need for increased resources or dietitian time.