Effectiveness of Probiotics to Treat End Stage Renal Disease
Effectiveness of Probiotics to Treat End Stage Renal Disease
Intestinal microbiota has recently emerged as an important player in the progression and
 complications of chronic kidney disease(CKD). And drug therapy which selects the gut as a
 target has raised lots of concern. It has been reported that the composition of intestinal
 flora has changed in uremic patients. Specifically, imbalanced ecosystem has higher number of
 pathogens such as Clostridia, Enterobacteria,and lower number of beneficial microbes such as
 Lactobacilli and Bifidobacteria. This modification of intestinal flora can strongly increase
 transformation of amino acids into Uremic Retention solutes, e.g., indoxyl-sulfate (IS),
 p-cresyl sulfate (PCS), which are so called gut-derived uremic toxins. The dysbiosis also
 contributes to an increase in intestinal permeability by disrupting the colonic epithelial
 tight junction,which may subsequently lead to translocation of endotoxin and bacteria into
 the host's internal environment,resulting in systemic micro-inflammation.Also all of these
 can promote the progression of renal failure and the incidence of cardiovascular
 complications,renal osteodystrophy and anemia.Probiotics is defined by the World Health
 Organization as 'live microorganisms that, when administered in adequate amounts, confer a
 health benefit on the host'. Probiotics are being increasingly used for various pathologic
 conditions.It is said that probiotics have a therapeutic role in maintaining a metabolically
 balanced gastrointestinal tract (GIT).And in our previous study,the investigators found that
 in uremic rats,lactobacillus acidophilus can relieve bacterial translocation and decrease the
 level of inflammatory markers.So our study is mainly designed to investigate whether
 probiotics can modulate the balance of intestinal ecosystem, prevent the bacterial
 translocation from gut and alleviate the systemic inflammation in hemodialysis(HD) patients.
This study is a single-centre, double-blind, placebo-controlled, randomised trial.
 Participants will undergo a 2 week run-in period, followed by randomisation to either
 probiotics supplements or placebo for 6 months. The study population are hemodialysis
 patients from Dialysis Department in First Affiliated Hospital of Xi'an Jiaotong University.
 The Dialysis Department have 400 patients who regularly come to receive dialysis therapy
 three times a week.It's relatively easy for us to follow up and collect data.Patients who
 meet the criteria and are able to provide informed consent will be recruited.Then
 computer-generated randomisation of participants to treatment order will be undertaken by an
 external statistical consultant. This process of allocation will conceal the randomisation
 order to researchers and participants. In addition, the supplements will be packed off-site
 with a generic label.

 After randomization,baseline data will be collected and all participants will undergo
 face-to-face dietary education with a dietitian, incorporating standard hemodialysis
 education during the first week of run-in.In the week following, and throughout the
 intervention, patients will be encouraged to maintain stable protein and fibre intakes, with
 specific attention to maintaining the same sources of these nutrients.Participants' dietary
 intakes during the study will be assessed every month using a semi-quantitative food
 frequency questionnaire. And when the trial starts, questionnaires and biological samples
 will be performed and collected at the corresponding time. All serious adverse events will be
 reported to the ethics committee, whether deemed to be intervention related or not. Adherence
 to supplements will be measured by pill count every two weeks.

 This study is an explorative clinical trial.And in the absence of any data about the effect
 of probiotics on hemodialysis patients intestinal and serum microbiota,sample size can't be
 calculated.Data will be reported as s mean±SD if normally distributed and as median(25-75%
 percentiles) if not. The Shapiro-Wilk test is performed to assess whether data are normally
 distributed. Statistical comparisons of normally distributed data are performed using
 Student's t-test. Mann-Whitney U-test is used to compare the rank variables measuring
 gastrointestinal symptoms in probiotics and placebo groups. The threshold for statistical
 significance is at p values <0.05. And an external statistical consultant from our Clinical
 Research Center will be involved in the data validation and analysis activities.
Inclusion Criteria:

 -  maintenance hemodialysis patients(MHP),dialysis age>3 months;

 -  signed informed consent.

 Exclusion Criteria:

 -  intolerance to whole milk and dairy products;

 -  patients with kidney transplant, with severe infections, sever heart disease and liver
 disease, malignancy, autoimmune disorders, severe malnutrition, or clinical conditions
 requiring artificial feeding;

 -  pregnant or nursing women;

 -  patients with known gastro-intestinal disease (i.e.,inflammatory bowel disease,crohn's
 disease,ulcerative colitis),receiving or have received radiation to the bowel or large
 bowel resection;

 -  use of antibiotics, prebiotics or probiotics in the past 4 weeks;