Beneficial Effect of Probiotics on Chronic Kidney Disease
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a randomized double blinded placebo control studies are performed in Chronic Kidney
      Disease (CKD) patients. After informed consent, intervention group receives probiotics
      containing 109 CFU B. bifidum, B.catenulatum, B. longum, and L.plantarm), while placebo group
      receives corn starch. In the first year the investigators examine the 60 peritoneal dialysis
      (PD) patients, in the second year the investigators do the 60 hemodialysis (HD) patients, and
      in the third year the investigators do the 60 stage 3 and 4 CKD patients. Primary endpoint is
      cardiovascular event, gastrointestinal symptoms, peritonitis in PD patients, and progression
      of stage 3 and 4 CKD. Values are compared between the groups by unpaired t test. X2 testis
      used to compare proportions between the groups. Relative risk and the number needed to treat,
      both with 95% CI, are used to describe the treatment effect of probiotics. A p value less
      than 0•05 is regarded as statistically significant.
    

Detailed description: 
      Chronic kidney disease (CKD) is a global health issue that has a substantial impact on
      affected individuals. The prognosis of dialysis patients is poor with 30 to 50 percent 5 year
      survival in nondiabetic patients and 25 percent in diabetics. Cardiovascular disease accounts
      for approximately half of death of dialysis patients Chronic inflammation, which is widely
      seen in long-term dialysis patients, is associated with malnutrition, atherosclerosis and an
      increased mortality risk. Inflammatory markers such as C-reactive protein (CRP),IL-6, Il-18
      and TNF-α, are elevated in dialysis and can predict cardiovascular event and all-cause
      mortality.

      Probiotics are microorganisms that have beneficial properties for the host. Three described
      benefits include suppression of growth or epithelial binding/invasion by pathogenic bacteria,
      improvement of intestinal barrier function and modulation the immune systems.

      Several probiotics preparations induce protective cytokines, including IL-10, and suppress
      proinflammatory cytokines, such as TNF-α and IL-6. Intestinal microflora is deranged in
      hemodialysis (HD) patients as an increase in aerobic bacteria such as E. coli and a decrease
      in anaerobic bacteria such as Bifidobacterium. One study reported that oral administration of
      ifidobacterium longum in a gastroresistant seamless capsule decreases the the pre-HD serum
      levels of homocysteine and indoxyl sulfate. Another small-scale study from Japan showed that
      synbiotics containing lactobacilli and can reduce serum level of p-Cresol in HD patients.
      High-serum p-cresyl sulfate and indoxyl sulfate levels were associated with renal
      progression. Serum concentrations of p-cresol are independently associated with overall
      mortality and cardiovascular disease in HD patients. The aim of the study is 1. to evaluate
      the difference of intestinal microflora between CKD patients and healthy controls; 2. to
      evaluate whether the investigators can reduce cardiovascular events in CKD patients, and
      peritonitis in peritoneal dialysis (PD) patients, retard the progression of stage 3 and 4 CKD
      patients, and decrease circulating inflammatory markers(CRP, IL-6,IL-18, TNF-α), indoxyl
      sulfate, p-cresol and homocysteine after probiotics treatment.

      Randomized double blinded placebo control studies are performed in CKD patients. After
      informed consent, intervention group receives probiotics containing 109 CFU B. bifidum,
      B.catenulatum, B. longum, and L.plantarm), while placebo group receives corn starch. In the
      first year the investigators examine the 60 PD patients, in the second year the investigators
      do the 60 HD patients,and in the third year the investigators do the 60 stage 3 and 4 CKD
      patients. Primary endpoint is cardiovascular event, gastrointestinal symptoms, peritonitis in
      PD patients, and progression of stage 3 and 4 CKD. Values are compared between the groups by
      unpaired t test. X2 testis used to compare proportions between the groups. Relative risk and
      the number needed to treat, both with 95% CI, are used to describe the treatment effect of
      probiotics. A p value less than 0·05 is regarded as statistically significant.
    

Intervention name(s): Probiotics; Cornstarch
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations; placebo will be given in 6 months
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention