title: Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. Effect of microbial cell preparation on renal profile and liver function among type 2 diabetics: a randomized controlled trial Randomized Controlled Trial of Strain-Specific Probiotic Formulation (Renadyl) in Dialysis Patients Effect of probiotics on human blood urea levels in patients with chronic renal failure. Synbiotic Supplementations for Azotemia in Patients With Chronic Kidney Disease: a Randomized Controlled Trial. Effects of a symbiotic on gut microbiota in Mexican patients with end-stage renal disease. The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND AND OBJECTIVES The generation of key uremic nephrovascular toxins , indoxyl sulfate ( IS ) , and p-cresyl sulfate ( PCS ) , is attributed to the dysbiotic gut microbiota in CKD . The aim of our study was to evaluate whether synbiotic ( pre- and probiotic ) therapy alters the gut microbiota and reduces serum concentrations of microbiome-generated uremic toxins , IS and PCS , in patients with CKD . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Predialysis adult participants with CKD ( eGFR=10 - 30 ml/min per 1.73 m(2 ) ) were recruited between January 5 , 2013 and November 12 , 2013 to a r and omized , double-blind , placebo-controlled , crossover trial of synbiotic therapy over 6 weeks ( 4-week washout ) . The primary outcome was serum IS . Secondary outcomes included serum PCS , stool microbiota profile , eGFR , proteinuria-albuminuria , urinary kidney injury molecule-1 , serum inflammatory biomarkers ( IL-1β , IL-6 , IL-10 , and TNF-α ) , serum oxidative stress biomarkers ( F2-isoprostanes and glutathione peroxidase ) , serum LPS , patient-reported health , Gastrointestinal Symptom Score , and dietary intake . A prespecified subgroup analysis explored the effect of antibiotic use on treatment effect . RESULTS Of 37 individuals r and omized ( age = 69±10 years old ; 57 % men ; eGFR=24±8 ml/min per 1.73 m(2 ) ) , 31 completed the study .  Synbiotic therapy did not significantly reduce serum IS ( -2 μmol/L ; 95 % confidence interval [ 95 % CI ] , -5 to 1 μmol/L ) but did significantly reduce serum PCS ( -14 μmol/L ; 95 % CI , -27 to -2 μmol/L ) . Decreases in both PCS and IS concentrations were more pronounced in patients who did not receive antibiotics during the study ( n=21 ; serum PCS , -25 μmol/L ; 95 % CI , -38 to -12 μmol/L ; serum IS , -5 μmol/L ; 95 % CI , -8 to -1 μmol/L ) . Synbiotics also altered the stool microbiome , particularly with enrichment of Bifidobacterium and depletion of Ruminococcaceae . Except for an increase in albuminuria of 38 mg/24 h ( P=0.03 ) in the synbiotic arm , no changes were observed in the other secondary outcomes . CONCLUSION In patients with CKD , synbiotics did not significantly reduce serum IS but did decrease serum PCS and favorably modified the stool microbiome . Large-scale clinical trials are justified Background The beneficial effect of probiotics on renal profile and liver function has been reported among patients with chronic kidney disease and fatty liver respectively . However , its effect on renal profile and liver function among type 2 diabetic individuals has not been fully understood . To investigate the effect of microbial cell preparation on renal profile and liver function tests among type 2 diabetic individuals . Methods A r and omized , double-blind , parallel-group , controlled clinical trial was conducted on a total of 136 type 2 diabetics age 30 - 70 years old in a teaching hospital in Kuala Lumpur , Malaysia . Subjects were r and omly assigned to receive microbial cell preparation ( N = 68 ) or a placebo ( N = 68 ) for 12 weeks . The outcomes measured at baseline , week 6 , and week 12 and included changes in renal profile ( Sodium , Potassium , Urea , Creatinine , Glomerular Filtration Rate ) , and liver function tests ( Albumin , Total Protein , Alkaline Phosphatase , Alanine Aminotransferase , Aspartate Aminotransferase ) . Intention to treat ( ITT ) analysis was performed on all the recruited subjects , while per protocol ( PP ) analysis was conducted on those who completed the trial with good compliance . Result The urea levels significantly declined in the probiotic group . Serum urea levels reduced from 4.26 mmol/L to 4.04 mmol/L in Probiotic Group while it increased in Placebo Group from 4.03 mmol/L to 4.24 mmol/L. These changes were significant between groups in ITT analysis ( p = 0.018 ) . Other parameters did not change significantly between groups . Conclusion 12 weeks supplementation with daily dosage of 6 × 1010 Colony Forming Units of multi-strain microbial cell preparation significantly improved urea levels . Trial registration ( Clinical trials : # NCT01752803 Background . Primary goal of this r and omized , double-blind , placebo-controlled crossover study of Renadyl in end-stage renal disease patients was to assess the safety and efficacy of Renadyl measured through improvement in quality of life or reduction in levels of known uremic toxins . Secondary goal was to investigate the effects on several biomarkers of inflammation and oxidative stress . Methods . Two 2-month treatment periods separated by 2-month washout and crossover , with physical examinations , venous blood testing , and quality of life question naires completed at each visit . Data were analyzed with SAS V9.2 . Results . 22 subjects ( 79 % ) completed the study . Observed trends were as follows ( none reaching statistical significance ): decline in WBC count ( −0.51 × 109/L , P = 0.057 ) and reductions in levels of C-reactive protein ( −8.61 mg/L , P = 0.071 ) and total indoxyl glucuronide ( −0.11 mg% , P = 0.058 ) . No statistically significant changes were observed in other uremic toxin levels or measures of QOL . Conclusions . Renadyl appeared to be safe to administer to ESRD patients on hemodialysis . Stability in QOL assessment is an encouraging result for a patient cohort in such advanced stage of kidney disease . Efficacy could not be confirmed definitively , primarily due to small sample size and low statistical power — further studies are warranted INTRODUCTION Patients with chronic kidney disease ( CKD ) show an increase in bowel aerobic bacteria that produce uremic toxins and decreased anaerobic bacteria as bifidobacteria and lactobacillus . The latter can be used as probiotics . The probiotic with greater availability in Mexico , is the lactobacillus casei shirota ( LcS ) , currently there is no known LcS specified dose that produces a benefit to the patient with CKD . OBJECTIVE To determine the effectiveness of two different LcS doses in achieving a decrease in urea concentrations of at least 10 % in patients with KDOQI stage 3 and stage 4 CKD . METODOLOGY : A simple r and omized , controlled clinical trial . Out patients treated at the National Institute of Medical Sciences and Nutrition Salvador Zubirán in México D.F. Patients were provided the LcS , as follows : Group A : 8 x 10(9 ) colony-forming units ( CFU ) and Group B : 16 x 10(9 ) CFU . Patients were followed-up for eight weeks , and baseline and final sample s were obtained to calculate the basal and final concentrations , respectively , of blood urea and serum creatinine ( CrS ) . During the follow-up , both groups consumed a diet of 30 kcal/kg/weight and 0.8 g/kg/weight of protein , and a food diary was made to assess both the adherence to the diet  and  LcS.  RESULTS Thirty patients with CKD were evaluated . When analyzing the percentage change between the different doses , a decrease > 10 % was found in the blood urea concentrations for patients treated with the 16 x 109 dose , which was significant with respect to the baseline measurement . CONCLUSION There was a > 10 % decrease in the serum urea concentrations with LcS in patients with stage 3 and 4 CRF INTRODUCTION Chronic kidney disease ( CKD ) is a progressive and irreversible impairment of kidney function ; if it progresses to the end-stage of CKD , dialysis or kidney transplant is needed . In general , there are no definitive treatment to slow the progression of CKD . This study aim ed to determine the effect of synbiotic supplementations on azotemia in patients with CKD . MATERIAL S AND METHODS A r and omized controlled trial was conducted on 66 patients with CKD ( stages 3 and 4 ) . The participants were r and omly divided into 2 groups to receive synbiotic supplement , 1000 mg/d , and placebo ( 2 capsules a day ) for 6 weeks . At the beginning and end of the study , blood parameters and kidney function were evaluated . RESULTS Of the 66 patients studied , 16 patients ( 24.2 % ) were women and 50 ( 75.8 % ) were men . The mean age and body mass index of the participants were 61 ± 7.65 years and 28.52 ± 4.06 kg/m2 , respectively .  The level of blood urea nitrogen showed a significant reduction following the intake of synbiotic supplement ( from 40.80 ± 22.11 mg/dL to 36.14 ± 20.52 mg/dL , P = .01 ) . Serum creatinine , uric acid , and other indicators of kidney function showed no significant change . CONCLUSIONS The intake of synbiotic supplement could reduce blood urea nitrogen in patients with CKD in stages 3 and 4 ; however , it had no effect on the other markers of kidney function OBJECTIVES Gut microbiota provides beneficial effects under physiological conditions , but is able to contribute to inflammatory diseases in susceptible individuals . Thus , we design ed this study to test whether additional intake of symbiotic gel affects specific modifications of gut microbiota in patients with end-stage renal disease ( ESRD ) . METHODS Eighteen patients with ESRD diagnosis with renal replacement therapy ( hemodialysis ) were included in this study . They were r and omly assigned to 2 treatment groups : ( 1 ) test group ( nutritional counseling + symbiotic ) and ( 2 ) control group ( nutritional counseling + placebo ) . Clinical history and the evaluation of Gastrointestinal Symptom Rating Scale were performed . Gut microbiota composition was analyzed by real-time polymerase chain reaction from fecal sample s. All subjects were followed for 2 months . RESULTS Bifidobacterial counts were higher in the second sample s ( mean : 5.5 ± 1.72 log10 cells/g ) than in first sample s ( 4.2 ± 0.88 log 10 cells/g ) in the patients of the test group ( P = .0344 ) . Also , lactobacilli counts had a little decrease in the test group ( 2.3 ± 0.75 to 2.0 ± 0.88 log 10 cells/g ) and the control group ( 2.2 ± 0.90 to 1.8 ± 1.33 log 10 cells/g ) , between the first and the second sample s. Gastrointestinal symptoms scores ( scale 8 - 40 ) were reduced in the test group ( start 12 [ 10 - 14 ] and end 9 [ 8 - 10 ] ) compared with control group ( start 11 [ 8 - 21 ] and end 11 [ 9 - 15 ] ) . CONCLUSIONS Short-term symbiotic treatment in patients with ESRD can lead to the increase of Bifidobacterium counts , maintaining the intestinal microbial balance Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha ( TNF-α ) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality . Endotoxin is an important source and also another marker of inflammation in patients with chronic kidney disease . The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis ( PD ) patients . The decline of residual renal function , peritonitis episodes , and cardiovascular events were also recorded . From July 2011 to June 2012 , a r and omised , double-blind , placebo-controlled trial was conducted in PD patients . The intervention group received one capsule of probiotics containing 10(9 ) cfu Bifobacterium bifidum A218 , 10(9 ) cfu Bifidobacterium catenulatum A302 , 10(9 ) cfu Bifidobacterium longum A101 , and 10(9 ) cfu Lactobacillus plantarum A87 daily for six months , while the placebo group received similar capsules containing maltodextrin for the same duration . Levels of serum TNF-α , interferon gamma , IL-5 , IL-6 , IL-10 , IL-17 , and endotoxin were measured before and six months after intervention . 39 patients completed the study ( 21 in the probiotics group and 18 in the placebo group ) . In patients receiving probiotics , levels of serum TNF-α , IL-5 , IL-6 , and endotoxin significantly decreased after six months of treatment , while levels of serum IL-10 significantly increased . In contrast , there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months . In addition , the residual renal function was preserved in patients receiving probiotics . In conclusion , probiotics could significantly reduce the serum levels of endotoxin , pro-inflammatory cytokines ( TNF-α and IL-6 ) , IL-5 , increase the serum levels of anti-inflammatory cytokine ( IL-10 ) , and preserve residual renal function in PD patients
target: Most of the included articles reported positive effects in renal function and decreased levels of urea , blood urea nitrogen , ammonia , plasma p-cresol , p-cresyl sulfate , and indoxyl sulfate
background: ABSTRACT Chronic kidney disease ( CKD ) is a syndrome caused by the progressive reduction of renal function .
  This study aim ed to systematic ally examine the effects of supplementation with probiotics in the treatment of CKD .