Effect of Prebiotics and/or Probiotics on Uremic Toxins and Inflammation Markers in Peritoneal Dialysis Patients
Effect of Prebiotics and/or Probiotics on Uremic Toxins and Inflammation Markers in Peritoneal Dialysis Patients
End-stage renal disease (ESRD) is a world public health problem, with high morbidity and
 mortality. Cardiovascular disease is the main cause of mortality in ESRD; uremic toxin
 retention and inflammation are considered non-traditional risk factors, as they have an
 active role in atherosclerosis and vascular calcification pathogenesis in dialysis patients.

 Uremic toxins may be generated by internal protein metabolism, however, some toxins that
 can't be efficiently eliminated by dialysis such as indoxyl sulphate and p-cresyl sulphate
 (protein bound toxins), are generated by the microbial metabolism in the large intestine by
 proteolytic bacteria, and may diffuse easily through the intestinal lumen, as a leaky gut
 characterizes kidney disease.

 The gut has been recognized as a potential source of inflammation in ESRD patients;
 accumulation of nitrogen compounds, presence of gastrointestinal symptoms, dietary changes
 and multiple drugs and supplements use, stimulates microbiota alterations as bacterial
 overgrowth and translocation. These phenomena, may active the immune system, promoting local
 and systemic inflammation, which in turn has negative effects increasing endothelial
 dysfunction, muscle catabolism, insulin and erythropoietin resistance, and decreases
 appetite.

 Some methods have been proposed to decrease inflammation and uremic toxin accumulation, as
 more efficient dialysis and anti-inflammatory drugs; however, some of them have limited
 efficacy and high cost. Nutritional treatments focused on modifying intestinal environment,
 as pre- and probiotics have promising effects by altering production and absorption of uremic
 toxins and decreasing inflammation; nevertheless, there is scarce information regarding its
 use and their role in ESRD, particularly in peritoneal dialysis, which is a widely used
 therapy in México. Furthermore, there is no clinical study comparing the effectiveness of
 prebiotics, probiotics, and symbiotics on serum concentrations of uremic toxins and
 inflammation in ESRD patients. It is possible that the administration of a nutritional
 supplement of probiotics and/or prebiotics decreases the serum concentrations of uremic
 toxins and inflammation markers in ESRD patients on automated peritoneal dialysis compared to
 placebo.
Objective:

 The aim of the present study is to evaluate and to compare the effect of a nutritional
 supplement of probiotics and/or prebiotics on serum concentrations of uremic toxins and
 inflammatory markers compared to placebo, in automated peritoneal dialysis patients.

 Sample size:

 For the sample size calculation a mean differences formula was used, with a 95% confidence
 level, a 80% sample power and accuracy of 0.05. As a reference, the study of Salmean YA, 2015
 was considered; in this study, the administration of pea fiber + inulin during 12 weeks in
 chronic kidney disease patients, significantly decreased (p<0.05) serum concentrations of
 p-cresol (5.82 ± 1.72 mg/L) in comparison to placebo (7.25 ± 1.74 mg/L). After substituting
 formula values and adding 20% of possible losses during follow-up, the sample size is: 28
 patients.

 Additionally, sample size calculation was made considering other outcomes. In the study of
 Xie LN, 2015, the administration of high-fermentable soluble fiber in ESRD patients on
 hemodialysis during 6 weeks, significantly decreased (p<0.05) inflammation markers:
 C-reactive protein (CRP), tumour necrosis factor alpha (TNFa) and interleukin 6 (IL-6) (4.8 ±
 4.5 pg/mL, 10.1 ± 1.4 pg/mL, 31.8 ± 5.3 mg/L, respectively) compared to control group (9.5 ±
 5.6 pg/mL, 13.1 ± 2.4 pg/mL, 51.5 ± 14.6 mg/L). After substituting the formula, sample size
 was 19, 7, and 5 for CRP, TNFa and IL-6, respectively.

 Thus, the highest value was finally used: 28 patients for intervention group.

 Statistical analysis:

 Quantitative variables will be shown as mean and standard deviation or median (25-75
 percentiles) according to their parametric or non-parametric distribution; Qualitative
 variables will be shown as frequency and percentage. Intergroup comparisons will be performed
 with χ2 or Fisher test for qualitative variables and one-way ANOVA or Kruskal-Wallis test for
 quantitative variables as appropriate. For intra-group comparisons Mc Nemar test will be used
 for qualitative variables and paired T-test, Wilcoxon, repeated-measures or Friedman ANOVA
 for quantitative variables as appropriate. An intention to treat analysis will be performed.
Inclusion Criteria:

 -  >3 months on automated peritoneal dialysis treatment

 -  Signed informed consent

 Exclusion Criteria:

 -  ESRD of inflammatory cause (lupus, vasculitis, collagenopathies)

 -  Intake of probiotics, prebiotics or fiber in the last 3 months

 -  Use of anti-inflammatory drugs or nutritional supplements (immunossuppresants,
 pentoxifylline, NSAIDs, omega-3)

 -  Treated with antibiotics or sevelamer

 -  Treated with research drugs or participants in any clinical trial

 -  Peritonitis or active infection 2 weeks prior the study

 -  Any medical condition affecting intestinal absorption (inflammatory bowel disease,
 short bowel syndrome, bariatric surgery) or severe dysmotility

 -  Severe malnutrition

 -  Previous kidney transplantation

 -  Serious diseases altering the fina outcomes of the study: decompensated heart failure,
 chronic liver disease, cancer, AIDS.