Table 1.
Summary of clinical trials on probiotic treatment used in patients with advanced CKD stage 3–5ND.
| Reference | Study Population | Country/Region | Type of Study | Sample Size | Endpoint Observed | Probiotic Type and Intervention Duration | Remarks | |
|---|---|---|---|---|---|---|---|---|
| Andreana De Mauri et al. [28] | eGFR < 25 mL/min/1.73 m2, non-dialysis | Italy | A single-centre, double-blind, placebo-controlled, randomized trial | 60 patients | Uremic toxins, nutritional status, quality of life, the progression to end stage renal disease and dialysis initiation | a New formulation of probiotics (Bifidobacterium longum and Lactobacillus reuteri) 3 months |
Probiotics to LPD may have an additional beneficial effect on the control and modulation of microbiota-derived and proatherogenic toxins in CKD patients | |
| I-Kuan Wang et al. [39] | CKD—Animal Model and CKD 3–5 patients | Taiwan | Animal studies and patients with stage 3–5 CKD and not on dialysis |
C57BL/6 mice, 53 patients | In vitro indole assay for the probiotics treatment of CKD, clinical symptoms and pathological findings of mice with CKD; clinical outcomes of the human: the rate of decline of the eGFR, serum levels of endotoxin and proinflammatory cytokines, stool form and gastrointestinal symptoms |
Lactobacillus acidophilus (TYCA06), Bifidobacterium longum subspecies infantis (BLI-02), and B. bifidum (VDD088) 6 months |
A combination of probiotics might attenuate renal function deterioration in CKD mice and human patients | |
| Sandra Wagner et al. [20] | CKD patients with stage 3–5 | France | Cross-sectional study | 888 patients | Association between inflammation and the frequency of yoghurt/probiotic intake |
Probiotics from yoghurts or dietary supplements 5 years |
Consumption of yoghurts and probiotics is associated with a lower risk of inflammation in patients with CKD | |
| Catherine McFarlane et al. [43] | CKD patients with stage 3–4 | Australia | A feasibility, double-blind, placebo-controlled, randomized trial | 68 patients | Recruitment and retention rates as well as acceptability of the intervention |
Synbiotic combined Bifidobacterium and Blautia spp for 12 months |
Long-term synbiotic and probiotics supplementation was feasible and acceptable to patients with CKD, and it modified the gastrointestinal microbiome | |
| Carmela Cosola et al. [13] | Stage IIIb-IV CKD Patients | Italy | A randomized, single-blind, placebo-controlled, pilot trial | 50 N = 23 CKD N = 27 healthy volunteers |
Serum levels of microbiota-derived uremic toxins | Lactobacilli and Bifidobacteria species 2 months |
The synbiotic NATUREN G ® is effective in reducing serum free IS, small intestine permeability, abdominal pain and constipation syndromes in stage IIIb-IV CKD patients | |
| Mariadelina Simeoni et al. [32] | Stage 3a of CKD | Italy | An open-label, randomized, placebo-controlled study | 28 patients | The impact of probiotic CKD administration protocol on fecal Lactobacillales and Bifidobacteria concentrations | Lactobacillales and Bifidobacteria 3 months |
High-quality probiotics can effectively correct inflammatory indices, iron status and iPTH stabilization | |
| Paola Vanessa Miranda Alatriste et al. [23] | CKD stage 3 and stage 4 | Mexico | A simple randomized, controlled clinical trial | 30 patients | Change in the blood urea concentrations for patients treated with the 16 × 10 9 dose lactobacillus casei shirota (LcS) |
Lactobacillus casei shirota (LcS) 8 weeks |
There was a >10% decrease in the serum urea concentrations with LcS in patients with stage 3 and 4 CRF | |
| B. Guida et al. [31] | CKD 3–4 stages | Italy | A double-blind, randomized placebo-controlled trial | 30 patients | Total plasma p-cresol median concentra- tions and gastrointestinal symptoms |
Synbiotic probinul-neutro 4 weeks |
Probinul-neutro lowered total plasma p-cresol concentrations but did not ameliorate gastrointestinal symptoms in non-dialyzed CKD patients | |
| Amanda de Faria Barros et al. [42] | Non-dialysis CKD patients (stages 3–5) | Brazil | A randomized, double-blind, placebo-controlled trial |
30 patients | Uremic toxins (cresyl sulfate, urea and TMAO) and inflammatory markers (IL-6 level and CRP) |
Streptococcus thermophilus, Lactobacillus acidophilus and Bifidobacteria for 3 months |
Probiotic supplementation did not result in expected benefits for non-dialysis CKD patients | |
| Natarajan Ranganathan et al. [12] | CKD stages 3 and 4 | USA | A prospective, randomized, double-blind, placebo controlled crossover trial |
46 patients | Biochemical parameters: blood urea nitrogen (BUN), serum creatinine, and uric acid and quality of life (QOL) | A mix of L. acidophilus KB27, B. longum KB31, and S. thermophilus KB19, for a total of 1.5 × 10 10 CFU 3 months |
Supporting the use of the chosen probiotic formulation for bowel-based toxic solute extraction; QOL and BUN levels showed statistically significant differences in outcome between placebo and probiotic treatment | |
| Megan Rossi et al. [29] | CKD stages 4 and 5 not on dialysis | Australia | A randomized, double-blind, placebo-controlled, crossover trial |
37 patients | p-cresyl sulfate (PCS) and indoxyl sulfate (IS); secondary outcomes include inflammatory markers and stool microbiota profile | Synbiotic therapy combined with Lactobacillus, Bifidobacteria, and Streptococcus 6 weeks |
In patients with CKD, probiotics combined synbiotics did not significantly reduce serum IS but did decrease serum PCS and favorably modified the stool microbiome | |
| Ruben Poesen et al. [27] | CKD 3b-4 stages | Belgium | A randomized, placebo-controlled, double-blind, cross-over study | 40 patients | Primary outcome on serum levels of microbial metabolites and secondary outcome on 24 h urinary excretion of microbial metabolites and HOMA-IR | Prebiotic arabinoxylan oligosaccharides (AXOS) (10 g twice daily) and maltodextrin for 4 weeks | Could not demonstrate an influence of prebiotic AXOS on microbiota derived uremic retention solutes and insulin resistance in patients with CKD not yet on dialysis | |