Effectiveness of Microecological Preparations for Improving Renal Function and Metabolic Profiles in Patients With Chronic Kidney Disease

Background Determining whether microecological preparations, including probiotics, prebiotics, and synbiotics, are beneficial for patients with chronic kidney disease (CKD) has been debated. Moreover, determining which preparation has the best effect remains unclear. In this study, we performed a network meta-analysis of randomized clinical trials (RCTs) to address these questions. Methods MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials were searched. Eligible RCTs with patients with CKD who received intervention measures involving probiotics, prebiotics, and/or synbiotics were included. The outcome indicators included changes in renal function, lipid profiles, inflammatory factors, and oxidative stress factors. Results Twenty-eight RCTs with 1,373 patients were ultimately included. Probiotics showed greater effect in lowering serum creatinine [mean difference (MD) −0.21, 95% confidence interval (CI) −0.34, −0.09] and triglycerides (MD −9.98, 95% CI −19.47, −0.49) than the placebo, with the largest surface area under the cumulative ranking curve, while prebiotics and synbiotics showed no advantages. Probiotics were also able to reduce malondialdehyde (MDA) (MD −0.54, 95% CI −0.96, −0.13) and increase glutathione (MD 72.86, 95% CI 25.44, 120.29). Prebiotics showed greater efficacy in decreasing high-sensitivity C-reactive protein (MD −2.06, 95% CI −3.79, −0.32) and tumor necrosis factor-α (MD −2.65, 95% CI −3.91, −1.39). Synbiotics showed a partially synergistic function in reducing MDA (MD −0.66, 95% CI −1.23, −0.09) and high-sensitivity C-reactive protein (MD −2.01, 95% CI −3.87, −0.16) and increasing total antioxidant capacity (MD 145.20, 95% CI 9.32, 281.08). Conclusion The results indicated that microbial supplements improved renal function and lipid profiles and favorably affected measures of oxidative stress and inflammation in patients with CKD. After thorough consideration, probiotics provide the most comprehensive and beneficial effects for patients with CKD and might be used as the best choice for microecological preparations. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022295497, PROSPERO 2022, identifier: CRD42022295497.

[1]  D. Zou,et al.  The effects of probiotic supplementation on renal function, inflammation, and oxidative stress in diabetic nephropathy: A systematic review and meta-analysis of randomized controlled trials , 2021, Materials Express.

[2]  L. Gesualdo,et al.  An Innovative Synbiotic Formulation Decreases Free Serum Indoxyl Sulfate, Small Intestine Permeability and Ameliorates Gastrointestinal Symptoms in a Randomized Pilot Trial in Stage IIIb-IV CKD Patients , 2021, Toxins.

[3]  Qing Wang,et al.  Probiotics ameliorates glycemic control of patients with diabetic nephropathy: A randomized clinical study , 2021, Journal of clinical laboratory analysis.

[4]  L. Nakao,et al.  Effect of Unripe Banana Flour on Gut-Derived Uremic Toxins in Individuals Undergoing Peritoneal Dialysis: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial , 2021, Nutrients.

[5]  S. Agah,et al.  Effect of Probiotic, Prebiotic, and Synbiotic Supplementation on Cardiometabolic and Oxidative Stress Parameters in Patients with Chronic Kidney Disease: a Systematic Review and Meta-analysis. , 2021, Clinical therapeutics.

[6]  S. Helmy,et al.  Efficacy of probiotic supplementation in patients with diabetic nephropathy: A systematic review and meta-analysis. , 2020, Clinical nutrition ESPEN.

[7]  G. Reid,et al.  The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics , 2020, Nature Reviews Gastroenterology & Hepatology.

[8]  E. Orenes-Piñero,et al.  Intestinal microbiota alterations in chronic kidney disease and the influence of dietary components , 2020, Critical reviews in food science and nutrition.

[9]  Weijun Huang,et al.  Probiotics, prebiotics, and synbiotics for the improvement of metabolic profiles in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials , 2020, Critical reviews in food science and nutrition.

[10]  Xiping Xu,et al.  Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents , 2020, Gut.

[11]  M. Usami,et al.  Prebiotics Improved the Defecation Status via Changes in the Microbiota and Short-chain Fatty Acids in Hemodialysis Patients. , 2020, The Kobe journal of medical sciences.

[12]  N. L. Rukavina Mikusic,et al.  Gut microbiota and chronic kidney disease: evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis , 2020, Pflügers Archiv - European Journal of Physiology.

[13]  A. Feizi,et al.  Effects of synbiotic supplementation on microbiota-derived protein-bound uremic toxins, systemic inflammation, and biochemical parameters in patients on hemodialysis: A double-blind, placebo-controlled, randomized clinical trial. , 2019, Nutrition.

[14]  S. Pennathur,et al.  Lipids and Cardiovascular Risk with CKD. , 2019, Clinical journal of the American Society of Nephrology : CJASN.

[15]  K. Lempert Probiotics and CKD Progression: Are Creatinine-Based Estimates of GFR Applicable? , 2019, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[16]  David W. Johnson,et al.  Prebiotic, Probiotic, and Synbiotic Supplementation in Chronic Kidney Disease: A Systematic Review and Meta-analysis. , 2019, Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

[17]  N. Vaziri,et al.  Amylose resistant starch (HAM‐RS2) supplementation increases the proportion of Faecalibacterium bacteria in end‐stage renal disease patients: Microbial analysis from a randomized placebo‐controlled trial , 2019, Hemodialysis international. International Symposium on Home Hemodialysis.

[18]  Behzad Abedi,et al.  Effects of fermentable high fiber diet supplementation on gut derived and conventional nitrogenous product in patients on maintenance hemodialysis: a randomized controlled trial , 2019, Nutrition & Metabolism.

[19]  M. Miri,et al.  A synbiotic supplement for inflammation and oxidative stress and lipid abnormalities in hemodialysis patients , 2019, Hemodialysis international. International Symposium on Home Hemodialysis.

[20]  Neda Haghighat,et al.  Effects of Synbiotics and Probiotics Supplementation on Serum Levels of Endotoxin, Heat Shock Protein 70 Antibodies and Inflammatory Markers in Hemodialysis Patients: a Randomized Double-Blinded Controlled Trial , 2019, Probiotics and Antimicrobial Proteins.

[21]  W. Xiong,et al.  Oxidative Stress and Renal Fibrosis: Mechanisms and Therapies. , 2019, Advances in experimental medicine and biology.

[22]  P. Stenvinkel,et al.  Effects of Probiotic Supplementation on Trimethylamine-N-Oxide Plasma Levels in Hemodialysis Patients: a Pilot Study , 2019, Probiotics and Antimicrobial Proteins.

[23]  D. Bolignano,et al.  Oxidative Stress and Kidney Function: A Brief Update. , 2019, Current pharmaceutical design.

[24]  M. Tajabadi-Ebrahimi,et al.  The Effects of Synbiotic Supplementation on Metabolic Status in Diabetic Patients Undergoing Hemodialysis: a Randomized, Double-Blinded, Placebo-Controlled Trial , 2018, Probiotics and Antimicrobial Proteins.

[25]  L. Nakao,et al.  Could resistant starch supplementation improve inflammatory and oxidative stress biomarkers and uremic toxins levels in hemodialysis patients? A pilot randomized controlled trial. , 2018, Food & function.

[26]  A. Barzegari,et al.  Effect of Lactobacillus Rhamnosus on serum uremic toxins (phenol and P-Cresol) in hemodialysis patients: A double blind randomized clinical trial. , 2018, Clinical nutrition ESPEN.

[27]  L. Jia,et al.  Efficacy of Probiotics Supplementation On Chronic Kidney Disease: a Systematic Review and Meta-Analysis , 2018, Kidney and Blood Pressure Research.

[28]  N. Vaziri,et al.  Effect of high amylose resistant starch (HAM‐RS2) supplementation on biomarkers of inflammation and oxidative stress in hemodialysis patients: a randomized clinical trial , 2018, Hemodialysis international. International Symposium on Home Hemodialysis.

[29]  Z. Asemi,et al.  Metabolic and genetic response to probiotics supplementation in patients with diabetic nephropathy: a randomized, double-blind, placebo-controlled trial. , 2018, Food & function.

[30]  H. Tavakolipour,et al.  The Effects of Probiotic Honey Consumption on Metabolic Status in Patients with Diabetic Nephropathy: a Randomized, Double-Blind, Controlled Trial , 2018, Probiotics and Antimicrobial Proteins.

[31]  A. Van Schepdael,et al.  Oxidative stress in chronic kidney disease , 2018, Pediatric Nephrology.

[32]  M. Andreucci,et al.  An open-label, randomized, placebo-controlled study on the effectiveness of a novel probiotics administration protocol (ProbiotiCKD) in patients with mild renal insufficiency (stage 3a of CKD) , 2018, European Journal of Nutrition.

[33]  K. Campbell,et al.  Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: a randomized controlled trial. , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[34]  C. Thongprayoon,et al.  The effects of probiotics on renal function and uremic toxins in patients with chronic kidney disease; a meta-analysis of randomized controlled trials , 2018 .

[35]  M. Delgado-Rodríguez,et al.  Systematic review and meta-analysis. , 2017, Medicina intensiva.

[36]  R. Ghiasvand,et al.  Effects of probiotic soy milk on lipid panel in type 2 diabetic patients with nephropathy: A double-blind randomized clinical trial , 2018 .

[37]  D. Fouque,et al.  Probiotic Supplementation in Chronic Kidney Disease: A Double-blind, Randomized, Placebo-controlled Trial. , 2018, Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

[38]  F. Violi,et al.  Oxidative stress and cardiovascular disease: new insights. , 2018, Kardiologia polska.

[39]  In-Soo Shin,et al.  Network meta-analysis: application and practice using Stata , 2017, Epidemiology and health.

[40]  B. Guida,et al.  Effect of a Short-Course Treatment with Synbiotics on Plasma p-Cresol Concentration in Kidney Transplant Recipients , 2017, Journal of the American College of Nutrition.

[41]  A. Feizi,et al.  The Impact of Probiotic Soy Milk Consumption on Oxidative Stress Among Type 2 Diabetic Kidney Disease Patients: A Randomized Controlled Clinical Trial. , 2017, Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

[42]  M. Farajollahi,et al.  The effects of probiotic supplement on hemoglobin in chronic renal failure patients under hemodialysis: A randomized clinical trial , 2017, Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences.

[43]  A. Webster,et al.  Chronic Kidney Disease , 2017, The Lancet.

[44]  Ahmad Esmaillzadeh,et al.  Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects. , 2017, Kidney international.

[45]  D. Huson,et al.  Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD-Related Systemic Inflammation. , 2017, Journal of the American Society of Nephrology : JASN.

[46]  David W. Johnson,et al.  Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. , 2016, Clinical journal of the American Society of Nephrology : CJASN.

[47]  F. Heidari,et al.  Synbiotic Supplementations for Azotemia in Patients With Chronic Kidney Disease: a Randomized Controlled Trial. , 2016, Iranian journal of kidney diseases.

[48]  J. V. van Putten,et al.  Redirection of Epithelial Immune Responses by Short-Chain Fatty Acids through Inhibition of Histone Deacetylases , 2015, Front. Immunol..

[49]  Kristian Thorlund,et al.  The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and Explanations , 2015, Annals of Internal Medicine.

[50]  G. García-García,et al.  Effect of a symbiotic gel (Lactobacillus acidophilus + Bifidobacterium lactis + inulin) on presence and severity of gastrointestinal symptoms in hemodialysis patients. , 2015, Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

[51]  L. Xie,et al.  Effects of fermentable dietary fiber supplementation on oxidative and inflammatory status in hemodialysis patients. , 2015, International journal of clinical and experimental medicine.

[52]  H. Sies,et al.  Oxidative stress: a concept in redox biology and medicine , 2015, Redox biology.

[53]  T. Meyer,et al.  Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients. , 2014, Clinical journal of the American Society of Nephrology : CJASN.

[54]  G. Schmidt,et al.  New insights , 2004 .

[55]  A. Levin,et al.  Practice Guideline , 2020, Encyclopedia of Behavioral Medicine.

[56]  Hsin-Chieh Yeh,et al.  Effect of the 2011 vs 2003 duty hour regulation-compliant models on sleep duration, trainee education, and continuity of patient care among internal medicine house staff: a randomized trial. , 2013, JAMA internal medicine.

[57]  内田隆一,et al.  小児急性嘔吐下痢症に対する五苓散の効果:バングラデシュにおけるRandomized,Double‐blind,Controlled Trial , 2012 .

[58]  J. Sterne,et al.  The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials , 2011, BMJ : British Medical Journal.

[59]  C. Bias The Cochrane Collaboration's tool for assessing risk of bias in randomised trials , 2011 .

[60]  Michele Tarsilla Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[61]  I. Harris,et al.  A Systematic Review and Meta-Analysis of Randomized Controlled Trials , 2010 .

[62]  D. Silverstein Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease , 2009, Pediatric Nephrology.

[63]  A. Sanabria,et al.  Randomized controlled trial. , 2005, World journal of surgery.

[64]  Thomas R. Riley,et al.  A Randomized Double-blind Placebo-controlled Trial , 2004 .

[65]  C. Baird,et al.  The pilot study. , 2000, Orthopedic nursing.

[66]  D. Salsburg,et al.  A Randomized Controlled Clinical Trial , 2016 .

[67]  E. Glaser The randomized clinical trial. , 1972, The New England journal of medicine.