Clinical efficacy of probiotics, prebiotics, and synbiotics on uremic toxins and renal function in patients with kidney disease: An umbrella meta-analysis

Chou-Yi Hsu ¹ Mohammad Rudiansyah ² Saade Abdalkareem Jasim ³ Renuka Jyothi.S ⁴ Ashwani Kumar ⁵ Alexey Yumashev ⁶ Jaafaru Sani Mohammed ⁷ Aashna Sinha ⁸ Farideh Alizadeh ⁹ Abebe Tesfaye ^10*

• ¹ Chia Nan University of Pharmacy and Science, Tainan, Tainan County, Taiwan
• ² Lambung Mangkurat University, Banjarmasin, South Kalimantan, Indonesia
• ³ University of Fallujah, Fallujah, Iraq
• ⁴ Jain University, Bengaluru, Karnataka, India
• ⁵ Vivekananda Global University, Jaipur, Rajasthan, India
• ⁶ I.M. Sechenov First Moscow State Medical University, Moscow, Moscow Oblast, Russia
• ⁷ Tishk International University (TIU), Erbil, Iraq
• ⁸ Uttaranchal University, Dehradun, Uttarakhand, India
• ⁹ University of Babylon, Hillah, Babil, Iraq
• ¹⁰ Addis Ababa University, Addis Ababa, Ethiopia

Background: It has been suggested that supplementation with prebiotics, probiotics, and synbiotics (pre-, pro-and synbiotics) may decrease improve uremic toxins and improve renal function in patients with kidney disease. Nonetheless, recent meta-analysis have presented conflicting findings. This umbrella meta-analysis examined the effectiveness of pre-, pro-and synbiotics on uremic toxins and renal function in patients with diabetic nephropathy (DN), chronic kidney disease (CKD), and end-stage renal disease (ESRD). Nonetheless, the outcomes of recent meta-analyses have presented conflicting viewpoints.Methods: A systematic search in Web of Science, Scopus, and PubMed databases was conducted to obtain pertinent studies. The outcomes included the concentrations of toxic metabolites (endotoxin, p-cresol sulfate, and indoxyl sulfate) and kidney function biomarkers (serum creatinine (Cr), urea, uric acid, blood urea nitrogen (BUN), albumin (Alb), and urinary Alb/Cr ratio). Standardized mean differences (SMD) with 95% confidence intervals (CI) were applied to test the effects.Results: Twenty-one meta-analyses with 13,116 patients were analyzed. Treatment with prebiotics and probiotics was effective in reducing the levels of toxic metabolites among ESRD patients, but not in CKD, especially when administered for ≥ 12 weeks. Microbiota-driven therapy improved kidney function in individuals with DN by lowering serum Cr, urea, BUN and urinary Alb/Cr ratio when given for a short term (< 12 weeks) and at a lower dosage (< 30×10^9 CFU), however, no favorable effect on kidney function was found for CKD and ESRD patients.Probiotics and prebiotics are promising alternative therapies to reduce toxic metabolites in ESRD and improve renal function in DN.