Table 3. Summary of Clinical Trials Examining the Use of Probiotics in Patients with Chronic Kidney Diseasea.
| study design/intervention duration/country | probiotics | dosage | main findings | ref |
|---|---|---|---|---|
| a retrospective study | Lactobacillus (Lactiplantibacillus) plantarum MFM30-3 | 1 × 1010 CFU/day | • reduction of creatinine | (77) |
| kidney transplatation patients (n = 24) | Lactobacilus (Lacticaseibacillus) paracasei MFM 18 | • improvement of eGFR | ||
| 3 months | ||||
| Taiwan | ||||
| a single-arm pilot study | • powder sachet (2 g): | 2 sachets/day | • fecal SCFAs increased significantly | (73) |
| hemodialysis patients (n = 18) | Bifidobacterium bifidum BGN4: 7 × 109 CFU | • reduction of serum calprotectin, a marker of acute inflammation, decreased significantly | ||
| 3 months | Bifidobacterium longum BORI: 2 × 109 CFU | • serum TNF-α and IL-6 upon LPS stimulation significantly decreased | ||
| Korea | • reduced systemic inflammatory responses were associated with an increase in Tregs and a decrease in proinflammatory monocytes | |||
| a randomized, single-blind, placebo-controlled pilot trial | • synbiotic bag: | 2 bags/day | • reduction of serum free IS | (76) |
| CKD stage 3b-4 patients (n = 47) | Lactobacillus (Lacticaseibacillus) casei LC4P1: 2.4 × 109 | • reduction of small intestinal permeability | ||
| 2 months | Bifidobacterium animalis BLC1: 2.4 × 109 | • amelioration of abdominal pain and constipation syndrome | ||
| Italy | fructooligosaccharides 2.5 g | |||
| inulin 2.5 g | ||||
| natural antioxidants (quercetin 0.064 g, resveratrol 0.023 g, and proanthocyanidins 0.013 g) | ||||
| a randomized, double-blinded, placebo-controlled clinical trial | Lactobacillus acidophilus | 2 × 1012 CFU/day | • improvement of gastrointestinal symptoms | (98) |
| hemodialysis patients (n = 18) | Bifidobacterium bifidum | 2.31 g/day | • elevation of Bifidobacterium | |
| 2 months | inulin | |||
| Mexico | ||||
| a double-blind, randomized clinical trial | Lactobacillus (Lactiplantibacillus) plantarum A87 | 4 × 1010 CFU/day | • reduction of serum CRP, glucose, and syndecan-1 (endothelial lesion marker) | (100) |
| hemodialysis patients (n = 70) | Lactobacillus (Lacticaseibacillus) rhamnosus | |||
| 3 months | Bifidobacterium bifidum A218 | |||
| Brazil | Bifidobacterium longum A101 | |||
| a double-blind, randomized, placebo-controlled clinical trial | Lactobacilus (Lacticaseibacillus) casei | 1 g/day | • reduction of BUN and trend to decrease serum CRE | (78) |
| CKD stage 3–4 patients (eGFR = 15–59 mL/min per 1.73 m2) (n = 66) | Lactobacilus acidophilus | |||
| 6 weeks | Lactobacilus bulgarigus | |||
| Iran | Lactobacilus (Lacticaseibacillus) rhamnosus | |||
| Bifidobacterium breve | ||||
| Bifidobacterium longum | ||||
| Sterptococus thermophilus | ||||
| Fructooligosaccharides | ||||
| a double-blind, randomized, placebo-controlled clinical trial | Lactobacillus (Lacticaseibacillus) rhamnosus | 1.6 × 107 CFU/day | • reduction of serum p-cresol and phenol | (79) |
| hemodialysis patients (n = 42) | ||||
| 4 weeks | ||||
| Iran | ||||
| a double-blind, randomized, placebo-controlled trial | • powder packets (5 g): | 3 packets/day | • reduction of plasma p-cresol | (80) |
| nondialyzed CKD stage 3–4 patients (eGFR = 15–60 mL/min per 1.73 m2) (n = 30) | Lactobacillus (Lactiplantibacillus) plantarum: 5 × 1010 | |||
| 4 weeks | Lactobacillus (Lacticaseibacillus) casei subsp. rhamnosus: 2 × 109 | |||
| Italy | Lactobacillus gasseri: 2 × 109 | |||
| Bifidobacterium infantis: 1 × 109 | ||||
| Bifidobacterium longum: 1 × 109 | ||||
| Lactobacillus acidophilus: 1 × 109 | ||||
| Lactobacillus (Ligilactobacillus) salivarius: 1 × 109 | ||||
| Lactobacillus sporogenes: 1 × 109 | ||||
| Streptococcus thermophiles: 5 × 109 | ||||
| inulin: 2.2 g | ||||
| tapioca-resistant starch:1.3 g | ||||
| a single-arm pilot study | Bifidobacterium infantis | 6 × 108 CFU/day | reduction of fecal indole and p-cresol, and plasma indican | (81) |
| hemodialysis patients (n = 20) | Lactobacillus acidophilus | |||
| 4 weeks | Enterococcus faecalis | |||
| Japan | the ratio of probiotic strain: 1:1:1 | |||
| a prospective, single-arm study | Lactobacillus acidophilus La-14 | 1.5 × 1010 65 mg | • reduction of serum PCS, IS, IL-6, and MDA | (74) |
| hemodialysis patients (n = 30) | fructooligosaccharides | |||
| 8 weeks | ||||
| Bulgaria | ||||
| a randomized, double-blinded, placebo-controlled clinical trial | Lactococcus lactis subsp. lactis LL358 | 2 sachets/day | • reduction of serum IS | (82) |
| hemodialysis patients (n = 50) | Lactobaccillus (Ligilactobacillus) salivarius LS159 | 1 × 1011 CFU/day | ||
| 6 months | Lactobaccillus (Lactiplantibacillus) pentosus LPE588 | |||
| Taiwan | ||||
| a randomized, double-blinded, placebo-controlled clinical trial | Bifidobacterium longum NQ1501 | B. longum | • probiotics did not significantly alter species diversity (Chao1 and Shannon) of the fecal microbiome, but induced a rearrangement in the microbial composition | (83) |
| hemodialysis patients (n = 45) | Lactobacillus acidophilus YIT2004 | 3.7 × 109 CFU/day | ||
| 6 months | Enterococcus faecalis YIT0072 | L. acidophilus | ||
| China | 8.9 × 108 CFU/day | • probiotics reduced serum indole-3-acetic acid-O-glucuronide, m-cresol, p-cresol, and phenol of nondiabetic patients | ||
| E. faecalis | ||||
| 1.8 × 109 CFU/day | ||||
| a simple randomized, controlled clinical trial | Lactobacillus (Lacticaseibacillus) casei shirota 8 × 109 CFU in fermented dairy drink | 8 × 109 CFU/day | • reduction of blood urea in 16 × 109 CFU group | (84) |
| CKD stage 3–4 patients (eGFR = 15–59 mL/min per 1.73 m2) (n = 30) | 16 × 109 CFU/day | |||
| 2 months | ||||
| Mexico | ||||
| a double-blind, randomized, placebo-controlled trial | • synbiotic pill: | 2 pills/day | • reduction of serum IS and trend to decrease serum PCS and TMAO | (14) |
| nondialyzed CKD patients (eGFR = 15 −45 mL/min per 1.73 m2) (n = 34) | Lactobacillus acidophilus CBT LA1: 4 × 109 | • improvement of eGFR | ||
| 12 weeks | Lactobacillus (Lacticaseibacillus) casei CBT LC5: 4 × 109 | • decreased level of high-sensitivity CRP | ||
| Serbia | Bifidobacterium lactis CBT BL3: 8 × 109 | • enrichment of Bifidobacteria, Lactobacillus, and Subdoligranulum | ||
| inulin: 1.6 g | ||||
| a preliminary study | Lactobacillus (Lacticaseibacillus) casei Shirota (LcS) | 3 × 108 CFU/day | • reduction of serum p-cresol | (85) |
| hemodialysis patients (n = 9) | Bifidobacterium breve Yakult (BbY) | 5.01 g | • improvement of difficulty in defecation and increased stool quantity | |
| 2 weeks | galacto-oligosaccharides (GOS) | |||
| Japan | ||||
| a double-blind, randomized, placebo-controlled crossover study | Streptococus thermophilus KB19 | 1.8 × 1012 CFU/day | • the trend of reductions of serum CRP and total indoxyl glucuronide | (86) |
| hemodialysis patients (n = 22) | Lactobacillus acidophilus KB27 | |||
| 2 months | Bifidobacterium longum KB31 | |||
| USA | ||||
| a pilot-scale, randomized, double-blind, placebo-controlled trial | Lactobacillus acidophilus KB31 | 9 × 1010 CFU/day | • reduction of serum BUN and uric acid | (87) |
| CKD stage 3–4 patients (n = 13) | Bifidobacterium longum KB35 | • elevation of Lactobacillus and Streptococcus | ||
| 3 months | Streptococus thermophilus KB27 | • reduction of fecal pH | ||
| Canada | ||||
| a prospective, randomized, double-blind, placebo-controlled, crossover trial at five institutions | Streptococus thermophilus KB19 | 9 × 1010 CFU/day | • reduction of BUN and trend to decrease serum CRE and uric acid | (88) |
| CKD stage 3–4 patients (n = 46) | Lactobacillus acidophilus KB27 | • improvement of quality of life | ||
| 3 months | Bifidobacterium longum KB31 | |||
| USA, Canada, Nigeria, and Argentina | ||||
| a double-blinded, placebo-controlled, randomized clinical trial | Lactobacillus genera | 9 × 109 CFU/day | • reduction of serum PCS and trend to decrease serum IS | (89) |
| nondialyzed CKD stage 4–5 patients (eGFR = 10–30 mL/min per 1.73 m2) (n = 31) | Bifidobacteria genera | 15 g | • elevation of Bifidobacterium and trend to increase Lactobacillus | |
| 6 weeks | Streptococcus genera | |||
| Australia | with nine different strains | |||
| inulin | ||||
| fructo-oligosaccharides | ||||
| galacto-oligosaccharides (GOSs) | ||||
| a single-center, open-label, randomized, placebo-controlled study | • Enterelle capsule (0.377 g): | • week 1: Enterelle ×3/day | • probiotics-treated patients exhibited a significant reduction of urinary indican and 3-methyl-indole. | (90) |
| CKD stage 3a patients (eGFR = 45–60 mL/min per 1.73 m2) (n = 28) | Enterococcus faecium (UBEF-41) | • week 2–3 Bifiselle ×3/day | • Lactobacillales and bifidobacteria concentrations were increased in the probiotics group | |
| 15 weeks | Ramnoselle ×3/day | |||
| Italy | Lactobacillus acidophilus (LA-14) Saccharomyces cerevisiae subsp. Boulardii (MTCC-5375) | • Week 4–15: | ||
| • bifidobacteria capsule (0.455g): | Bifiselle ×2/day | |||
| Bifidobacterium brevis (BB03) | Ramnoselle ×2/day | |||
| Bifidobacterium bifidum (BB06) | ||||
| Bifidobacterium longum (BL05) | ||||
| • Ramnoselle capsule (0.455 g): | ||||
| Lactobacillus (Lacticaseibacillus) rhamnosus (HN-001) | ||||
| Lactobacillus (Lacticaseibacillus) rhamnosus (LR-32) | ||||
| Lactobacillus acidophilus (LA-14) | ||||
| • a preliminary study | Bifidobacterium longum | 3 × 109 CFU/day | reduction of serum IS | (91) |
| hemodialysis patients (n = 11) | ||||
| 5 weeks | ||||
| Japan | ||||
| a double-blinded, placebo-controlled, randomized clinical trial | Lactobacillus acidophilus NCFM | 11 × 106 CFU/day | • improvement of gastrointestinal symptoms | (99) |
| hemodialysis patients (n = 42) | Bifidobacterium lactis Bi-07 | 2.31 g/day | • the trend to decrease CRP | |
| 2 months | inulin | |||
| Mexico | ||||
| a randomized, double-blinded, placebo-controlled trial | Bifidobacterium bifidum A218 | 4 × 109 CFU/day | • reduction of serum endotoxin and proinflammatory cytokine (TNF-α, IL-6, and IL-5) | (75) |
| peritoneal dialysis patients (n = 39) | Bifidobacterium catenulatum A302 | • elevation of anti-inflammatory cytokine (IL-10) | ||
| 6 months | Bifidobacterium longum A101 | |||
| Taiwan | Lactobacillus (Lactiplantibacillus) plantarum A87 | |||
| the ratio of probiotic strain: 1:1:1:1 | ||||
| a single-arm pilot study | Lactobacillus acidophilus TYCA06 | 1 × 1010 CFU/day | • eGFR decline was significantly slower | (64) |
| nondialyzed CKD stage 3–5 patients (n = 38) | Bifidobacterium longum subsp. infantis BLI-02 | • serum TNF-α, IL-6, IL-18, and endotoxin were significantly decreased | ||
| 6 months | Bifidobacterium bifidum VDD088 | • improvement of gastrointestinal symptoms (borborygmus and flatulence) | ||
| Taiwan | the ratio of probiotic strain:1:1:1 | • the abundance of B. bifidum and B. breve increased significantly | ||
| a randomized, double-blinded, placebo-controlled clinical trial | Lactobacillus (Lacticaseibacillus) casei Zhang | 4 × 109 CFU/day | • log10 urine albumin-to-creatinine ratio (UACR) mildly increased in the probiotic group compared to a significant increase in the placebo group | (92) |
| nondialyzed CKD stage 3–5 patients (n = 62) | • the amplitude of the increase in CRE was lower in the probiotic group after 1 year observation | |||
| 3 months | • eGFR decline was slower in the probiotic group during the intervention and follow-up 7 months | |||
| China | • the diversity of intestinal flora did not change among groups | |||
a
CFU, colony-forming unit; CKD, chronic kidney disease; CRE, creatinine; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rates; IS, indoxyl sulfate; PCS, P-cresyl sulfate; TMAO, trimethylamine-N-oxide; SCFA, short-chain fatty acid; CRP, C-reactive protein; TNF-α, tumor necrosis factor-α; IL-5, interleukin-5; IL-6, interleukin-6; IL-10, interleukin-10; IL-18, interleukin-18; MDA, malondialdehyde.