Clinical trial NCT03228563: The Effect of Probiotics on Chronic Kidney Disease
Official title: The Effect of Probiotics on Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease
Probiotics
Renal Function
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
First posted: 2017-07-25
Enrollment: 148
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Probiotics could attenuate renal function deterioration in CKD patients.

Detailed description: Chronic kidney disease (CKD) is a global health issue that has a substantial impact on affected individuals. Chronic inflammation, which is widely seen in CKD including long-term dialysis patients, is associated with malnutrition, atherosclerosis and an increased mortality risk. Inflammatory markers such as C-reactive protein, IL-6, IL-18, and TNF-α, are elevated in dialysis patients and can predict cardiovascular event and all-cause mortality. Endotoxin is bacterial lipopolysaccharide, and makes up the outer membrane of Gram-negative bacteria. Endotoxin is also an important source and also a marker of inflammation in CKD.

The natural intestinal microbiota is altered in CKD patients as an increase in aerobic bacteria such as E. coli and a decrease in anaerobic bacteria such as Bifidobacterium. Dysbiosis might contribute to the chronic inflammatory state in dialysis patients through endotoxemia, induction of the pro-inflammatory cytokine, and production of uremic toxins through fermentation of protein in the large intestine. Probiotics containing Bifidobacterium species and Lactobacilli species could benefit the host by inhibiting the growth or epithelial invasion of pathogenic bacteria, enhancing the intestinal barrier function, and regulating the immune system.

Probiotics could suppress proinflammatory cytokines, such as TNF-α and IL-6 . In addition, probiotics could improve renal function parameters in uremic rats and significantly lower levels of blood urea nitrogen in stage 3 and 4 CKD patients. The aim of the present study is to evaluate:

1. Whether probiotics could retard the decline of renal function?
2. Whether probiotics could change microbiota?
3. Whether probiotics could reduce the serum levels of endotoxin and cytokines (TNF-α, IL-6, and IL-18)?
4. Whether probiotics could improve the gastrointestinal symptoms in CKD patients?

Estimated glomerular filtration rate, stool microbiota, serum cytokines and endotoxin, and gastrointestinal symptoms of stage 3-5 patients are measured before and after intervention. The Wilcoxon signed-rank and Wilcoxon rank-sum tests were used to compare intra- and intergroup differences for continuous variables, as appropriate. A p value less than 0.05 was considered significant.

Eligibility criteria: Healthy volunteers:

The criteria for healthy volunteers were: no hypertension (Blood pressure\<140/90mmHg), no diabetes (Glucose AC 70\~100mg/dl), no hyperlipidemia (Cholesterol Total 130\~200mg/dL、Triglyceride\<150mg/dL), no urinary protein (-) and normal renal function (eGFR\>90), after signing the consent form, the stool samples will be collected.

CKD patients:

Inclusion Criteria:

‧Stage 3-5 CKD patients, at least 20 years of age and regular follow-up for at least 6 months prior to enrollment.

Exclusion Criteria:

* Pregnancy.
* On immunosuppressive therapy.
* Active infectious condition.
* Acute kidney injury.
* Consuming other forms of probiotics.
* Taking antibiotics within 30 days prior to enrollment.

Primary outcomes:
measure: eGFR decline rate.
timeFrame: 12 months.
Secondary outcomes:
measure: Change rate in serum pro-inflammatory cytokines (TNF-α, IL6 and IL18) and endotoxin.
timeFrame: 12 months
measure: Average scores of gastrointestinal symptoms by questionnaire.
timeFrame: 12 months.
measure: Relative abundance of intestinal microbiota.
timeFrame: 12 months.
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: China Medical University Hospital
Study officials:
affiliation: China Medical University Hospital
name: I-kuan Wang
role: STUDY_DIRECTOR
References: