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Effect of Low-Protein Diet and Inulin on Microbiota and Clinical Parameters in Patients with Chronic Kidney Disease.

ABSTRACT: INTRODUCTION:The gut microbiota has coevolved with humans for a mutually beneficial coexistence and plays an important role in health and disease. A dysbiotic gut microbiome may contribute to progression to chronic kidney disease (CKD) and CKD-related complications such as cardiovascular disease. Microbiota modulation through the administration of prebiotics may represent an important therapeutic target. AIM:We sought to evaluate the effects of a low-protein diet (LPD) (0.6 g/kg/day) with or without the intake of the prebiotic inulin (19 g/day) on microbiota and clinical parameters in CKD patients. MATERIALS AND METHODS:We performed a longitudinal, prospective, controlled, and interventional study on 16 patients: 9 patients treated with LPD (0.6 g/kg/day) and inulin (19 g/day) and 7 patients (control group) treated only with LPD (0.6 g/kg/day). Clinical evaluations were performed and fecal samples were collected for a subsequent evaluation of the intestinal microbiota in all patients. These tests were carried out before the initiation of LPD, with or without inulin, at baseline (T0) and at 6 months (T2). The microbiota of 16 healthy control (HC) subjects was also analyzed in order to identify potential dysbiosis between patients and healthy subjects. RESULTS:Gut microbiota of CKD patients was different from that of healthy controls. The LPD was able to significantly increase the frequencies of Akkermansiaceae and Bacteroidaceae and decrease the frequencies of Christensenellaceae, Clostridiaceae, Lactobacillaceae, and Pasteurellaceae. Only Bifidobacteriaceae were increased when the LPD was accompanied by oral inulin intake. We showed a significant reduction of serum uric acid (SUA) and C-reactive protein (CRP) in patients treated with LPD and inulin (p = 0.018 and p = 0.003, respectively), an improvement in SF-36 (physical role functioning and general health perceptions; p = 0.03 and p = 0.01, respectively), and a significant increase of serum bicarbonate both in patients treated with LPD (p = 0.026) or with LPD and inulin (p = 0.01). Moreover, in patients treated with LPD and inulin, we observed a significant reduction in circulating tumor necrosis factor alpha (TNF-?) (p = 0.041) and plasma nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) (p = 0.027) levels. We did not find a significant difference in the circulating levels of Interleukin (IL)-1? (p = 0.529) and IL-6 (p = 0.828) in the two groups. CONCLUSIONS:LPD, associated or not with inulin, modified gut microbiota and modulated inflammatory and metabolic parameters in patients with CKD. Our results suggest that interventions attempting to modulate the gut microbiome may represent novel strategies to improve clinical outcomes in CKD patients and may provide useful therapeutic effects.

SUBMITTER: Lai S

PROVIDER: S-EPMC6950025 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Effect of Low-Protein Diet and Inulin on Microbiota and Clinical Parameters in Patients with Chronic Kidney Disease.

Lai Silvia S Molfino Alessio A Testorio Massimo M Perrotta Adolfo M AM Currado Annachiara A Pintus Giovanni G Pietrucci Daniele D Unida Valeria V La Rocca Davide D Biocca Silvia S Desideri Alessandro A

Nutrients 20191209 12

<h4>Introduction</h4>The gut microbiota has coevolved with humans for a mutually beneficial coexistence and plays an important role in health and disease. A dysbiotic gut microbiome may contribute to progression to chronic kidney disease (CKD) and CKD-related complications such as cardiovascular disease. Microbiota modulation through the administration of prebiotics may represent an important therapeutic target.<h4>Aim</h4>We sought to evaluate the effects of a low-protein diet (LPD) (0.6 g/kg/d ...[more]

PMID: 31818021

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Project description:Background: Although associations between low protein diet (LPD) and changes of gut microbiota have been reported; however, systematic discernment of the effects of LPD on diet-microbiome-host interaction in patients with chronic kidney disease (CKD) is lacking. Methods: We searched PUBMED and EMBASE for articles published on changes of gut microbiota associated with implementation of LPD in CKD patients until July 2021. Independent researchers extracted data and assessed risks of bias. We conducted meta-analyses of combine p-value, mean differences and random effects for gut microbiota and related metabolites. Study heterogeneity was measured by Tau2 and I2 statistic. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Five articles met inclusion criteria. The meta-analyses of gut microbiota exhibited enrichments of Lactobacillaceae (meta-p= 0.010), Bacteroidaceae (meta-p= 0.048) and Streptococcus anginosus (meta-p< 0.001), but revealed depletion of Bacteroides eggerthii (p=0.017) and Roseburia faecis (meta-p=0.019) in LPD patients compared to patients undergoing normal protein diet. The serum IS levels (mean difference: 0.68 ug/mL, 95% CI: -8.38-9.68, p= 0.89) and pCS levels (mean difference: -3.85 ug/mL, 95% CI: -15.49-7.78, p < 0.52) did not change between groups. We did not find significant differences on renal function associated with change of microbiota between groups (eGFR, mean difference: -7.21 mL/min/1.73 m2, 95% CI: -33.2-18.79, p= 0.59; blood urea nitrogen, mean difference: -6.8 mg/dL, 95% CI: -46.42-32.82, p= 0.74). Other clinical (sodium, potassium, phosphate, albumin, fasting sugar, uric acid, total cholesterol, triglycerides, C-reactive protein and hemoglobin) and anthropometric estimates (body mass index, systolic blood pressure and diastolic blood pressure) did not differ between the two groups. Conclusions: This systematic review and meta-analysis suggested that the effects of LPD on the microbiota were observed predominantly at the families and species levels but minimal on microbial diversity or richness. In the absence of global compositional microbiota shifts, the species-level changes appear insufficient to alter metabolic or clinical outputs.

Project description:ObjectiveThe benefits of a low-salt diet for patients with chronic kidney disease (CKD) are controversial. We conducted a systematic review and meta-analysis of the effect of a low-salt diet on major clinical outcomes.DesignSystematic review and meta-analysis.Data sourcesMEDLINE by Ovid, EMBASE and the Cochrane Library databases.Eligibility criteria for selecting studiesWe included randomised controlled trials (RCTs) and cohort studies that assessed the effect of a low-salt diet on the renal composite outcomes (more than 50% decline in estimated glomerular filtration rate (eGFR) during follow-up, doubling of serum creatinine or end-stage renal disease), rate of eGFR decline, change in proteinuria, all-cause mortality events, cardiovascular (CV) events, and changes in systolic blood pressure and diastolic blood pressure.Data extraction and synthesisTwo independent researchers extracted data and evaluated their quality. Relative risks (RRs) with 95% CIs were used for dichotomous data. Differences in means (MDs) or standardised mean differences (SMDs) with 95% CIs were used to pool continuous data. We used the Cochrane Collaboration risk-of-bias tool to evaluate the quality of RCTs, and Newcastle-Ottawa Scale to evaluate the quality of cohort studies.ResultsWe found 9948 potential research records. After removing duplicates, we reviewed the titles and abstracts, and screened the full text of 230 publications. Thirty-three studies with 101 077 participants were included. A low-salt diet produced a 28% reduction in renal composite outcome events (RR: 0.72; 95% CI: 0.58 to 0.89). No significant effects were found in terms of changes in proteinuria (SMD: -0.71; 95% CI: -1.66 to 0.24), rate of eGFR (decline MD: 1.16; 95% CI: -2.02 to 4.33), risk of all-cause mortality (RR: 0.92; 95% CI: 0.58 to 1.46) and CV events (RR: 1.01; 95% CI: 0.46 to 2.22).ConclusionA low-salt diet seems to reduce the risk for renal composite outcome events in patients with CKD. However, no compelling evidence indicated that such a diet would reduce the eGFR decline rate, proteinuria, incidence of all-cause mortality and CV events. Further, more definitive studies are needed.Prospero registration numberCRD42017072395.

Project description:The effect of a hydrolyzed protein diet on the fecal microbiota has not been studied in feline chronic enteropathy (CE). Our study aimed to (1) compare the fecal microbiota of cats with CE to control cats with no gastrointestinal signs and (2) determine the effect of a hydrolyzed protein diet on the fecal microbiota of cats with CE and whether this differs between dietary responders and non-responders. The fecal microbiome of cats with CE (n = 36) showed decreased α-diversity in terms of genus richness (P = 0.04) and increased β-diversity in terms of Bray-Curtis Dissimilarity (P < 0.001) compared to control cats (n = 14). Clostridium was the only genera significantly over-represented in cats with CE compared to control cats (adjusted P < 0.1). After 6-weeks of feeding the diet, fifteen cats were classified as responders and 18 as non-responders, based on clinical signs. At the genus level, α-diversity was increased in non-responders versus responders at diagnosis, but decreased after dietary intervention in both groups (P < 0.05). At the family level, non-responders became increasingly dissimilar after dietary intervention (P = 0.012). In general, the abundance of bacteria decreased with feeding a hydrolyzed diet, with the genera most significantly affected being more frequently observed in non-responders. Bifidobacterium was the only genus that increased significantly in abundance post-diet and this effect was observed in both responders and non-responders. Both Oscillibacter and Desulfovibrionaceae_unclassified were most abundant in non-responders at diagnosis but were rarely observed post diet in neither responders nor non-responders. Cats with CE had similar microbiota changes to those described in human inflammatory bowel disease. Whether the presence of Oscillibacter and Desulfovibrionaceae_unclassified are indicators of non-response to the diet at diagnosis requires further investigation. Despite the hydrolyzed diet reducing α-diversity in all cats with CE, this did not resolve gastrointestinal signs in some cats. However, responders metabolized the diet in a similar manner, reflected by sustained β-diversity, while the microbiome of non-responders became increasingly dissimilar compared to diagnosis at the family level. Therefore, the microbiome may not be as tightly regulated in cats with CE that are non-responders and therefore, these cats would require additional therapy for remission of clinical signs.

Project description:ObjectiveTo evaluate the effect of low-protein diet on kidney function in patients with diabetic nephropathy.DesignA systematic review and a meta-analysis of randomised controlled trials.Data sourcesMEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number (ISRCTN) Register and University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) from inception to 10 December 2012. Internet searches were also carried out with general search engines (Google and Google Scholar).Study selectionRandomised controlled trials that compared low-protein diet versus control diet and assessed the effects on kidney function, proteinuria, glycaemic control or nutritional status.Primary and secondary outcome measures and data synthesisThe primary outcome was a change in the glomerular filtration rate (GFR). The secondary outcomes were changes in proteinuria, post-treatment value of glycated haemoglobin A1C (HbA1c) and post-treatment value of serum albumin. The results were summarised as the mean difference for continuous outcomes and pooled by the random effects model. Subgroup analyses and sensitivity analyses were conducted regarding patient characteristics, intervention period, methodological quality and assessment of diet compliance. The assessment of diet compliance was performed based on the actual protein intake ratio (APIR) of the low-protein diet group to the control group.ResultsWe identified 13 randomised controlled trials enrolling 779 patients. A low-protein diet was associated with a significant improvement in GFR (5.82 ml/min/1.73 m(2), 95% CI 2.30 to 9.33, I(2)=92%; n=624). This effect was consistent across the subgroups of type of diabetes, stages of nephropathy and intervention period. However, GFR was improved only when diet compliance was fair (8.92, 95% CI 2.75 to 15.09, I(2)=92% for APIR <0.9 and 0.03, 95% CI -1.49 to 1.56, I(2)=90% for APIR ≥0.9). Proteinuria and serum albumin were not differed between the groups. HbA1c was slightly but significantly decreased in the low-protein diet group (-0.26%, 95% CI -0.35 to -0.18, I(2)=0%; n=536).ConclusionsLow-protein diet was significantly associated with improvement of diabetic nephropathy. The adverse effects of low-protein diet were not apparent such as worsening of glycaemic control and malnutrition.

Project description:BackgroundDietary protein restriction has long been thought to play an important role in the progression of chronic kidney disease (CKD); however, the effect of dietary protein on the rate of decline in kidney function remains controversial.ObjectiveWe undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the influence of protein restriction on chronic kidney disease.MethodOvid MEDLINE (from 1946 to March 5, 2016), EMBASE (from 1966 to March 5, 2016), and the Cochrane Library (Inception to March 5, 2016) were searched to identify RCTs comparing different levels of protein intake for at least 24 weeks in adult patients with CKD. The outcomes included kidney failure events, the rate of change in estimated glomerular filtration rate (eGFR) per year, all cause death events, and changes in proteinuria, serum phosphorus concentration, serum albumin, and body mass index (BMI).ResultsNineteen trials with 2492 subjects were analyzed. A low protein diet reduced the risk of kidney failure (odds ratio (OR) = 0.59, 95% CI: 0.41 to 0.85) and end-stage renal disease (ESRD) (OR = 0.64, 95% CI: 0.43 to 0.96), but did not produce a clear beneficial effect for all cause death events (OR = 1.17, 95% CI: 0.67 to 2.06). The change in the mean difference (MD) for the rate of decline in the eGFR was significant (MD: -1.85, P = 0.001), and for proteinuria (MD: -0.44, P = 0.02). A low protein diet also reduced the serum phosphorus concentration (MD: -0.37, 95% CI: -0.5 to -0.24) and BMI (MD: -0.61, 95% CI: -1.05 to -0.17). However the change in albumin presented no significant difference between two groups (MD: 0.23, 95% CI: -0.51 to 0.97).ConclusionsBased on the findings of our meta-analysis, protein-restricted diet may reduce the rate of decline in renal function and the risk of kidney failure for CKD populations, but did not produce a clear beneficial effect for all cause death events. Besides However, the optimal level of protein intake in different participants is left unanswered, and the nutritional status should be regarded with caution.

Project description:BackgroundRecent data pose the question whether conservative management of chronic kidney disease (CKD) by means of a low-protein diet can be a safe and effective means to avoid or defer transition to dialysis therapy without causing protein-energy wasting or cachexia. We aimed to systematically review and meta-analyse the controlled clinical trials with adequate participants in each trial, providing rigorous contemporary evidence of the impact of a low-protein diet in the management of uraemia and its complications in patients with CKD.MethodsWe searched MEDLINE (PubMed) and other sources for controlled trials on CKD to compare clinical management of CKD patients under various levels of dietary protein intake or to compare restricted protein intake with other interventions. Studies with similar patients, interventions, and outcomes were included in the meta-analyses.ResultsWe identified 16 controlled trials of low-protein diet in CKD that met the stringent qualification criteria including having 30 or more participants. Compared with diets with protein intake of >0.8 g/kg/day, diets with restricted protein intake (<0.8 g/kg/day) were associated with higher serum bicarbonate levels, lower phosphorus levels, lower azotemia, lower rates of progression to end-stage renal disease, and a trend towards lower rates of all-cause death. In addition, very-low-protein diets (protein intake <0.4 g/kg/day) were associated with greater preservation of kidney function and reduction in the rate of progression to end-stage renal disease. Safety and adherence to a low-protein diet was not inferior to a normal protein diet, and there was no difference in the rate of malnutrition or protein-energy wasting.ConclusionsIn this pooled analysis of moderate-size controlled trials, a low-protein diet appears to enhance the conservative management of non-dialysis-dependent CKD and may be considered as a potential option for CKD patients who wish to avoid or defer dialysis initiation and to slow down the progression of CKD, while the risk of protein-energy wasting and cachexia remains minimal.

Dataset Information

Effect of Low-Protein Diet and Inulin on Microbiota and Clinical Parameters in Patients with Chronic Kidney Disease.

Publications

Effect of Low-Protein Diet and Inulin on Microbiota and Clinical Parameters in Patients with Chronic Kidney Disease.

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