title: Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) Effects of Probiotic Supplementation on Trimethylamine-N-Oxide Plasma Levels in Hemodialysis Patients: a Pilot Study Probiotic dietary supplementation in patients with stage 3 and 4 chronic kidney disease: a 6-month pilot scale trial in Canada Probiotic Amelioration of Azotemia in 5/6th Nephrectomized Sprague-Dawley Rats Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: a randomized clinical trial. Effect of a symbiotic gel (Lactobacillus acidophilus + Bifidobacterium lactis + inulin) on presence and severity of gastrointestinal symptoms in hemodialysis patients. Randomized Controlled Trial of Strain-Specific Probiotic Formulation (Renadyl) in Dialysis Patients SYNbiotics Easing Renal failure by improving Gut microbiologY (SYNERGY): a protocol of placebo-controlled randomised cross-over trial Use of a probiotic to decrease enteric hyperoxaluria. Synbiotic Supplementations for Azotemia in Patients With Chronic Kidney Disease: a Randomized Controlled Trial. Dietary Changes Involving Bifidobacterium longum and Other Nutrients Delays Chronic Kidney Disease Progression Effects of a symbiotic on gut microbiota in Mexican patients with end-stage renal disease. Publication bias in clinical research Biomodulation of the toxic and nutritional effects of small bowel bacterial overgrowth in end-stage kidney disease using freeze-dried Lactobacillus acidophilus. Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial. Influence of prebiotic and probiotic supplementation on the progression of chronic kidney disease.
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 Gastrointestinal ( GI ) symptoms and irritable bowel ( IB ) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis ( CFS/ME ) . The aim of this study was to conduct a systematic review of these symptoms in CFS/ME , along with any evidence for probiotics as treatment . Pubmed , Scopus , Medline ( EBSCOHost ) and EMBASE data bases were search ed to source relevant studies for CFS/ME . The review included any studies examining GI symptoms , irritable bowel syndrome ( IBS ) and /or probiotic use . Studies were required to report criteria for CFS/ME and study design , intervention and outcome measures . Quality assessment was also completed to summarise the level of evidence available . A total of 3381 publications were returned using our search terms . Twenty-five studies were included in the review . R and omised control trials were the predominant study type ( n = 24 ) . Most of the studies identified examined the effect of  probiotic supplementation on the improvement of IB symptoms in IBS patients , or IB symptoms in CFS/ME patients , as well as some other significant secondary outcomes ( e.g. quality of life , other gastrointestinal symptoms , psychological symptoms ) . The level of evidence identified for the use of  probiotics  in IBS was excellent in quality ; however , the evidence available for the use of probiotic interventions in CFS/ME was poor and limited . There is currently insufficient evidence for the use of probiotics in CFS/ME patients , despite probiotic interventions being useful in IBS . The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall . St and ardisation of protocol s and methodology in these studies is required Components present in the diet , l-carnitine , choline , and betaine are metabolized by gut microbiota to produce metabolites such as trimethylamine-N-oxide ( TMAO ) that appear to promote cardiovascular disease in chronic kidney disease ( CKD ) patients . The objective of this pilot study was to evaluate the effects of probiotic supplementation for 3 months on plasma TMAO levels in CKD patients on hemodialysis ( HD ) . A r and omized , double-blind trial was performed in 21 patients [ 54.8 ± 10.4 years , nine men , BMI 26.1 ± 4.8 kg/m2 , dialysis vintage 68.5 ( 34.2–120.7 ) months ] . Ten patients were r and omly allocated to the placebo group and 11 to the probiotic group [ three capsules , totaling 9 × 1013 colony-forming units per day of Streptococcus thermophilus ( KB19 ) , Lactobacillus acidophilus ( KB27 ) , and Bifidobacteria longum ( KB31 ) . Plasma TMAO , choline , and betaine levels were measured by LC-MS/MS at baseline and after 3 months . While TMAO did not change after probiotic supplementation , there was a significant increase in betaine plasma levels . In contrast , the placebo group showed a significant decrease in plasma choline levels . Short-term probiotic supplementation does not appear to influence plasma TMAO levels in HD patients . Long-term studies are needed to determine whether probiotics may affect TMAO production in CKD patients ABSTRACT Aim : This was a pilot clinical trial to assess biochemical and clinical effects of an oral probiotic dietary supplement in chronic kidney disease ( CKD ) patients ( stages 3 and 4 ) . Methods : A prospect i ve , r and omized , double-blind , crossover , placebo-controlled , 6-month trial of probiotic bacteria was conducted in 16 out patients in Ontario , Canada . Primary endpoints included effect on hematologic , biochemical , and fecal variables , and on general well-being as assessed by quality of life ( QOL ) . These outcomes were evaluated from biochemical parameters , mainly blood urea nitrogen ( BUN ) , creatinine , uric acid , and C-reactive protein ( CRP ) as a general inflammatory marker . QOL was assessed on a subjective scale of 1 to 10 as the secondary parameter . Trial registration : This pilot study forms part of registered trial NCT00760162 . Results : A total of 13 patients completed the study . Three patients dropped out : one was the receiver of a transplant . The second dropped out for unknown reasons and the third died of myocardial infa rct ion ( unrelated to probiotic bacteria or the protocol ) . Among the 13 patients who completed the trial , the mean change in BUN concentration during the probiotic treatment period ( −2.93 mmol/L ) differed significantly ( p = 0.002 ) from the mean change in BUN concentration during the placebo period ( 4.52 mmol/L ) . In addition , the mean changes in uric acid concentration were moderate during the KB period ( 24.70 μmol/L ) versus during the placebo period ( 50.62 μmol/L , p = 0.050 ) , and the changes in serum creatinine concentration were insignificant . Neither gastrointestinal nor infectious complications were noted in any subject with improved QOL . Conclusion : Orally administered probiotic bacteria selected to metabolize nitrogenous wastes may be tolerated for as long as 6 months . A major limitation of this trial is its small size that may have precluded detection of changes in other biochemical or hematologic parameters that would be evident in larger cohorts . Extension of the evaluation of this probiotic bacterial mixture will include a dose escalation trial in a similar prospect i ve , placebo-controlled , and double-blind study site The present study was to test the hypothesis that selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into nontoxic compounds ; thereby , ameliorating the biochemical imbalance . Herein we describe a prospect i ve , blinded , placebo-controlled pilot study , using 5/6th nephrectomized Sprague Dawley rat as a chronic renal failure model . The study group consisted of 36 nephrectomized and 7 non-nephrectomized ( control ) rats . After two-week nephrectomy stabilization , cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens : ( A ) Control , ( B ) Placebo ( casein-based diet without probiotics ) , ( C ) Bacillus pasteurii , ( D ) Sporolac ® , ( E ) Kibow cocktail , ( F ) CHR Hansen Cocktail , and ( G ) ECONORMTM .  Subsequently , blood ( retro-orbital ) and urine ( collected for measurements of blood urea-nitrogen and creatinine respectively ) , body weight and bacterial counts ( feces ) were obtained at regular intervals . The study end-points were to determine if any of the probiotic dietary supplements facilitated , ( 1 ) decreased blood concentrations of uremic toxins , ( 2 ) altered renal function , and ( 3 ) prolonged survival . After 16 weeks of treatment , regimens C and D significantly prolonged the life span of uremic rats , in addition to showing a reduction in blood urea-nitrogen levels , concluding that supplementation of probiotic formulation to uremic rats slows the progression of azotemia , which may correlate with prolonged life span of uremic rats . Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure BACKGROUND AND AIMS In patients with chronic kidney disease ( CKD ) , alterations in gut microbiome are posited to be responsible for gastrointestinal symptoms and generation of p-cresol , a uremic toxin that has been associated with CKD progression and cardiovascular mortality . This pilot study investigated whether Probinul-neutro ® , a synbiotic that normalizes intestinal microflora , may lower plasma p-cresol concentrations and reduce gastrointestinal symptoms in non-dialyzed CKD patients . METHODS AND RESULTS This was a double-blind , r and omized placebo-controlled trial . Thirty patients on 3 - 4 CKD stages were r and omized to receive either Probinul neutro ® or placebo for 4 weeks . Total plasma p-cresol concentration was assessed at baseline , and 15 and 30 days after treatment start . At the same study times , ease and frequency of defecation , upper and lower abdominal pain , stool shape , borborygmi , and flatus were quantified by subjective assessment question naires . Compared to baseline total plasma p-cresol median concentrations on 15th and 30th day were significantly lower in patients receiving Probinul-neutro ® ( 2.31 and 0.78 vs. 3.05 μg/ml , p < 0.05 ; n = 18 ) ; no changes of plasma p-cresol concentrations were recorded in placebo-treated patients . No significant changes in gastrointestinal symptoms were observed during the study both in Probinul-neutro ® -treated and placebo-treated patients . CONCLUSION Probinul-neutro ® lowered total plasma p-cresol concentrations but did not ameliorate gastrointestinal symptoms in non-dialyzed CKD patients . Because high plasma concentrations of p-cresol in early phases of CKD are predictive of progression to end-stage renal disease , the results of our study suggest that synbiotics deserve attention as possible tools to delay CKD progression towards end-stage renal disease ( ESRD ) . CLINICAL TRIALSGOV IDENTIFIER NCT02008331 OBJECTIVE The study aim ed to assess the effect of a symbiotic gel on presence and severity of gastrointestinal symptoms ( GIS ) in hemodialysis patients . DESIGN A double-blinded , placebo-controlled , r and omized , clinical trial was design ed . The study was conducted at 2 public hospitals in Guadalajara , Mexico . SUBJECTS AND INTERVENTION Twenty-two patients were r and omized to the intervention group ( nutritional counseling + symbiotic gel )  and 20 patients were r and omized to the control group ( nutritional counseling + placebo )  , during 2 months of follow-up . MAIN OUTCOME MEASURE Presence and monthly episodes of GIS were assessed by direct interview and severity by using the self-administered GIS question naire . Additionally , biochemical parameters , inflammatory markers , and nutritional status ( dietary intake , subjective global assessment , anthropometry , and body composition ) were evaluated . RESULTS After a 2-month treatment , intervention group had a significant reduction in prevalence and monthly episodes of vomit , heartburn , and stomachache , as well as a significant decrease in GIS severity compared with control group . Moreover , intervention group had a greater yet not significant decrease in the prevalence of malnutrition and a trend to reduce their C-reactive protein and tumor necrosis factor α levels compared with control group . No symbiotic-related adverse side effects were shown in these patients . Clinical studies with longer follow-up and sample size are needed to confirm these results . CONCLUSIONS We concluded that administration of a symbiotic gel is a safe and simple way to improve common GIS in dialysis patients 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 Background Emerging evidence suggests modulating the microbiota in the large bowel of patients with chronic kidney disease ( CKD ) through pre- and /probiotic supplementation may inhibit the development of key nephrovascular toxins . To date , quality intervention trials investigating this novel treatment in CKD are lacking . The aim of SYNERGY is to assess the effectiveness of synbiotics ( co-administration of pre- and probiotics ) as a potential treatment targeting the synthesis of uremic toxins , specifically , indoxyl sulphate ( IS ) and p-cresyl sulphate ( PCS ) . Methods / design Thirty-seven patients with moderate to severe CKD ( Stage IV and V , pre-dialysis ) will be recruited to a double-blind , placebo-controlled , r and omised cross-over trial . Patients will be provided with synbiotic therapy or placebo for 6 weeks , with a 4 week washout before cross-over . The primary outcome is serum IS , total and free ( unbound ) concentrations , measured using ultra-performance liquid chromatography . Secondary outcomes include serum PCS , total and free ( unbound ) concentrations ; cardiovascular risk , measured by serum lipopolysaccharides , serum trimethylamine-N-oxide ( TMAO ) and inflammation and oxidative stress markers ; kidney damage , measured by 24 hour proteinuria and albuminuria , estimated glomerular filtration rate and renal tubule damage ( urinary kidney injury molecule-1 ) ; patients ’ self assessed quality of life ; and gastrointestinal symptoms . In addition , the effects on the community structure of the stool microbiota will be explored in a subset of patients to vali date the mechanistic rationale underpinning the synbiotic therapy . Discussion IS and PCS are two novel uremic toxins implicated in both cardiovascular disease ( CVD ) and progression of CKD . Preliminary studies indicate that synbiotic therapy maybe a promising strategy when considering a targeted , tolerable and cost-efficient therapy for lowering serum IS and PCS concentrations . This trial will provide high quality ‘ proof-of-concept ’ data to eluci date both the efficacy of synbiotic therapy for lowering the toxins and whether reductions in serum IS and PCS translate into clinical benefits . Considering the potential of pre- and probiotics to not only shift toxin levels , but to also impede CVD and CKD progression , SYNERGY will provide vital insight into the effectiveness of this innocuous nutritional therapy . Trial Registration Universal Trial Number : U1111 - 1142 - 4363 . Australian New Zeal and Clinical Trials Registry Number : ACTRN12613000493741 , date registered : 2nd May 2013 BACKGROUND Patients with inflammatory bowel disease have a 10- to 100-fold increased risk of nephrolithiasis , with enteric hyperoxaluria being the major risk factor for these and other patients with fat malabsorptive states . Endogenous components of the intestinal microflora can potentially limit dietary oxalate absorption . METHODS Ten patients were studied with chronic fat malabsorption , calcium oxalate stones , and hyperoxaluria thought to be caused by jejunoileal bypass ( 1 ) and Roux-en-Y gastric bypass surgery for obesity ( 4 ) , dumping syndrome secondary to gastrectomy ( 2 ) , celiac sprue ( 1 ) , chronic pancreatitis ( 1 ) , and ulcerative colitis in remission ( 1 ) . For 3 months , patients received increasing doses of a lactic acid bacteria mixture ( Oxadrop ) , VSL Pharmaceuticals ) , followed by a washout month . Twenty-four-hour urine collection s were performed at baseline and after each month . RESULTS Mean urinary oxalate excretion fell by 19 % after 1 month ( 1 dose per day , P < 0.05 ) , and oxalate excretion remained reduced by 24 % during the second month ( 2 doses per day , P < 0.05 ) . During the third month on 3 doses per day oxalate excretion increased slightly , so that the mean was close to the baseline established off treatment . Urinary oxalate again fell 20 % from baseline during the washout period . Calcium oxalate supersaturation was reduced while on Oxadrop , largely due to the decrease in oxalate excretion , although mean changes did not reach statistical significance . CONCLUSION Manipulation of gastrointestinal ( GI ) flora can influence urinary oxalate excretion to reduce urinary supersaturation levels . These changes could have a salutary effect on stone formation rates . Further studies will be needed to establish the optimal dosing regimen 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 Background : Recent studies suggest that prebiotic and /or probiotic treatments ameliorate kidney function in humans and animals by improving the gut environment . However , the gut microbiota and kidney disease interactions remain to be determined . This study investigated whether synbiotics modulate the gut microbiota and ameliorate kidney function using a rat model of chronic kidney disease ( CKD ) . As uremic toxins are associated with CKD-related mineral and bone disorder , the secondary aim was to evaluate the relationship between synbiotics and secondary hyperparathyroidism ( SHPT ) . Methods : 5/6 nephrectomy ( Nx ) rats were developed as the CKD model . Sham-operated ( sham ) rats were used as the control . To investigate the effectiveness of prebiotics ( glutamine , dietary fiber , and oligosaccharide ) and probiotics ( Bifidobacterium longum strain ; GFOB diet ) , rats were r and omly assigned to 4 groups : Nx group fed the GFOB diet ( n = 10 ) ; Nx group fed the control ( CON ) diet ( n = 10 ) ; sham group fed the GFOB diet ( n = 5 ) ; and sham group fed the control diet ( n = 5 ) . Blood , feces , and kidney sample s were collected and analyzed . Results : Serum creatinine ( Cre ) and blood urea nitrogen in the Nx GFOB group were significantly lower than those in the Nx CON group . Serum indoxyl sulfate in the Nx GFOB group was lower than that in the Nx CON group , and significantly correlated with serum Cre . Inorganic phosphorus and intact parathyroid hormone in the Nx GFOB group were significantly lower than those in the Nx CON group . Conclusion : Improving the gut environment using synbiotics ameliorated kidney function and might be a pharmacological treatment for SHPT without any serious adverse events 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 In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies Small bowel bacterial overgrowth ( SBBO ) , well known to occur in end-stage kidney failure , is responsible for producing uremic toxins and contributing to the patient 's decreased nutritional well-being . In this study , 8 hemodialysis patients were treated with a course of oral Lactobacillus acidophilus ( LBA ) in an attempt to alter this SBBO . LBA treatment was effective in lowering 2 compounds generated in vivo . Serum dimethylamine ( DMA ) levels dropped from 224 + /- 47 to 154 + /- 47 micrograms/dl at the end of LBA treatment ( p < 0.001 ) . Nitrosodimethylamine , a carcinogen , levels also decreased significantly from 178 + /- 67 ( untreated ) to 83 + /- 49 ng/kg ( after LBA treatment ) . Patients nutritional status , assessed as serum albumin , body weight , caloric intake , midarm muscle area ( MAMA ) and appetite improved modestly , but not significantly . LBA changed small bowel pathobiology by modifying metabolic actions of SBBO , reducing in vivo generation of toxins and carcinogens and promoting nutrition with no adverse side effects Introduction Uremic syndrome consists of nitrogenous waste retention , deficiency in kidney-derived hormones , and reduced acid excretion , and , if untreated , may progress to coma and eventual death . Previous experience suggests that oral administration of a probiotic formulation of selected microbial strains may extend renoprotection via intraintestinal extraction of toxic waste solutes in patients with chronic kidney disease (CKD)stages 3 and 4 . This report presents preliminary data from a pilot study . Methods This was a 6-month prospect i ve , r and omized , double-blind , placebo-controlled crossover trial of a probiotic bacterial formulation conducted in four countries , at five institutions , on 46 out patients with CKD stages 3 an nd 4 : USA ( n=10 ) , Canada ( n=113 ) , Nigeria ( n=115 ) , and Argentina ( n=8 ) . Outcomes were compared using biochemical parameters : blood urea nitrogen ( BUN ) , serum creatinine , and uric acid . General well-being was assessed as a secondary parameter by a quality of life ( QQOL ) question naire on a subjective scale of 1–10 . Results Oral ingestion of probiotics ( 90 billion colony forming units [CFUs]/day ) was well tolerated and safe during the entire trial period at all sites . BUN levels decreased in 29 patients ( 63 % , P<0.05 ) , creatinine levels decreased in 20 patients ( 43 % , no statistical significance ) , and uric acid levels decreased in 15 patients ( 33 % , no statistical significance ) . Almost all subjects expressed a perceived substantial overall improvement in QOL ( 86 % , P<0.05 ) . Conclusion The main outcomes of this preliminary trial include a significant reduction of BUN , enhanced well-being , and absence of serious adverse effects , thus supporting the use of the chosen probiotic formulation for bowel-based toxic solute extraction . QOL and BUN levels showed statistically significant differences in outcome ( P<0.05 ) between placebo and probiotic treatment periods at all four sites ( 46 patients ) . A major limitation of this trial is the small sample size nd elated inconsistencies 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 BACKGROUND One of the main goals in chronic kidney disease ( CKD ) patients is to diminish the accumulation of uremic toxins and to slow the progression of renal failure . We investigated whether prebiotic and probiotic supplementation along with low protein diet retards the progression of CKD . METHODS This is a 12-month prospect i ve observation study with a r and omized control and open-label design . A total of 24 stable CKD stage III to V patients , who are not on renal replacement therapy , were enrolled in this study . Patients were r and omly assigned to 2 groups : low protein diet + prebiotic + probiotic supplementation ( N.=12 ) , receiving 3 tablets of prebiotic + probiotic supplementation daily for 6 months , and the control group receiving low protein diet only ( N.=12 ) . We examined the effects of prebiotic and probiotic supplementation on estimated glomerular filtration rate ( eGFR ) in CKD . RESULTS The declining GFR  during prebiotic and probiotic supplementation were significantly lower ( -11.6±8.6 vs. -3.4±4.6 mL/min per 1.73 m2 per year , 95 % CI -6.45 - -9.86 , P<0.001 ) than those with low protein diet alone . CONCLUSIONS Prebiotic and probiotic supplementation along with low protein diet delayed the progression of CKD
target: Conclusion Our study demonstrates potential beneficial effects of probiotics on inflammation , uremic toxins , and GI Symptoms in ESRD patients .
background: Background / Objectives We performed this systematic review and meta- analysis to evaluate effects of probiotics on inflammation , uremic toxins , and gastrointestinal ( GI ) symptoms in end-stage renal disease ( ESRD ) patients .