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.

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.

Inclusion Criteria:

1. receiving peritoneal dialysis for more than 3 months, at least 18 years of age, and GFR < 15 ml/min.
2. receiving hemodialysis dialysis for more than 3 months, at least 18 years of age, and GFR < 15 ml/min.
3. Stage 3 and 4 CKD patients

Exclusion Criteria:

• active infectious conditions within the last 30 days,
• pregnancy for female,
• autoimmune disease e.g. SLE.,
• cardiovascular events before.

1 month