Supplementary Material for: Efficacy of Probiotics Supplementation On Chronic Kidney Disease: a Systematic Review and Meta-Analysis

<b><i>Background/Aims:</i></b> Dysbiosis of the intestinal microbiota may accelerate the progression of chronic kidney disease (CKD) by increasing the levels of urea toxins. In recent years, probiotics have been recognized to maintain the physiological balance of the intestinal microbiota. In this study, we aim to assess the therapeutic effects of probiotics on CKD patients with and without dialysis via meta-analysis. <b><i>Methods:</i></b> We conducted a meta-analysis of randomized controlled trials (RCTs) by searching the databases of Pubmed, EMBASE and Cochrane Library (No. CRD42018093080). Studies on probiotics for treatment of CKD adults lasting for at least 4 weeks were selected. The primary outcomes were the levels of urea toxins, and the second outcomes were the levels of interleukin (IL)-6, C-reactive protein (CRP) and hemoglobin (Hb). The risk of bias was assessed by Cochrane Collaboration’ tool, and the quality of evidence was appraised with the Grading of Recommendation Assessment. Means and standard deviations were analyzed by random effects analysis. Stratified analysis was done and sensitivity analysis was performed when appropriate. <b><i>Results:</i></b> Totally, eight studies with 261 patients at CKD stage 3 to 5 with and without dialysis were included. We found a decrease of p-cresyl sulfate (PCS) of 3 studies with 125 subjects (<i>P</i> = 0.01, SMD -0.57, 95% CI, -0.99 to -0.14, <i>I<sup>2</sup></i> = 25%) and an increase of IL-6 in 3 studies with 134 subjects (<i>P</i> = 0.03, 95% CI, SMD 0.37, 0.03 to 0.72, <i>I<sup>2</sup></i> = 0%) in the probiotics groups. Analysis of serum creatinine (<i>P</i> = 0.47), blood urine nitrogen (<i>P</i> = 0.73), CRP (<i>P</i> = 0.55) and Hb (<i>P</i> = 0.49) yielded insignificant difference. <b><i>Conclusion:</i></b> Limited number of studies and small sample size are limitations of our study. Probiotics supplementation may reduce the levels of PCS and elevate the levels of IL-6 whereby protecting the intestinal epithelial barrier of patients with CKD.