Table 1.
Summary of main characteristics and findings of the RCTs reviewed.
| Study, Year (ref.) | Inclusion Criteria Exclusion Criteria |
Population Characteristics | Intervention | Control | Duration | Outcome(s) | Results | Notes |
|---|---|---|---|---|---|---|---|---|
| Bliss et al., 1996 [10] | CKD patients underwent low-protein diet for ≥4 months Liver diseases, HD, renal transplantation, active gastrointestinal bleeding, pregnancy or lactating |
n = 16 Men (%) = 63 Urea (mg/dL) = 50 ± 6 SCr (mg/dL) = 4.4 ± 0.8 |
Prebiotics (Gum arabic fiber, 25g twice/daily) (n = 16) |
Placebo (n = 16) |
Eight weeks | SCr (mg/dL) | End of treatment, 4.5 ± 3.2 vs. 4.7 ± 3.6 in prebiotic vs. placebo group (p = 0.12) | Single blind, cross-over Four drop-outs; per-protocol analysis performed |
| Urea (mg/dL) | End of treatment, 44 ± 20 vs. 52 ± 32 in prebiotic vs. placebo group (p < 0.05) | |||||||
| Younes et al., 2006 [11] | CKD patients underwent a restrictive protein diet (0.8g/kg/day) |
n = 9 Age (year) = 67.7 ± 11.5 Men (%) = 33 Urea (mmol/L) = 25 ± 5 CrCl (mL/min) = 25 ± 5 |
Prebiotics (Fermentable carbohydrate 40 g/day) (n = 9) |
Standard treatment (n = 9) |
10 weeks | CrCl (mL/min) | End of treatment, 24.2 ± 13.9 vs. 22.6 ± 12.2 in prebiotic vs. control group (p > 0.05) | Open label, cross-over Prebiotic supplementation consisted of 25 g of whole-meal bread, 4.5 g inulin and 10.5 g crude potato starch |
| SCr (µmol/L) | End of treatment, 339 ± 146 vs. 357 ± 143 in prebiotic vs. control group (p > 0.05) | |||||||
| Urea (mmol/L) | End of treatment, 20.2 ± 8.2 vs. 26.1 ± 8.7 in prebiotic vs. control group (p < 0.05) | |||||||
| Ranganathan et al., 2010* [12] Ranganathan et al., 2009 |
Stage 3–4 CKD patients Antibiotic treatment within 14 days before screening, drugs or alcohol dependence, HIV, liver disease, any medical, psychiatric, debilitating disease, anticoagulant therapy, pregnancy |
n = 46 Age (year) = ~56 Men (%) = 67 DM (%) = 41 |
Probiotics (two capsules thrice/daily) (n = 46) |
Placebo (n = 46) |
Six months | SCr (μmol/L) | End of treatment, 388.52±229.85 vs. 414.04±342.34 in probiotic vs. placebo group (p = 0.23) | Double blind, cross-over Each capsule (15 billion CFU) of probiotic supplementation contained L. acidophilus, B. longum and S. thermophilus Sixteen drop-outs; per-protocol analysis performed |
| BUN (µmol/L) | End of treatment, 23.82 ± 12.01 vs. 25.89 ± 15.14 in probiotic vs. placebo group (p = 0.039) | |||||||
| C-reactive protein (mg/L) (n = 13 pts) | End of treatment, mean change −5.32 ± 19.7 vs. 8.55 ± 20.1 in probiotic vs. placebo group (p = 0.24) | |||||||
| QoL | Improvement of QoL (1.54 ± 1.25) during probiotic group (p < 0.001) | |||||||
| Guida et al., 2014 [13] | Stage 3–4 CKD patients Renal transplant, severe infections and malnutrition, DM, malignancy, food intolerance, autoimmune disorders |
n = 30 Age (year) = 59.5 ± 13.1 Men (%) = 87 BMI (Kg/m2) = ~27.5 eGFR (mL/min) = ~29.2 |
Synbiotics (5g powder packets thrice/daily) (n = 18) |
Placebo (n = 12) |
Four weeks | eGFR (mL/min) | No difference between groups | Double blind Synbiotic formulation consisted of probiotic supplement (L. plantarum, 5 billion CFU, L. casei subsp. Rhamnosus, 2 billion CFU, L. gasseri, 2 billion CFU, Bifidobacterium infantis, 1 billion CFU, Bifidobacterium longum, 1 billion CFU, L. acidophilus, 1 billion CFU, L. salivarius, 1 billion CFU, L. sporogenes, 1 billion CFU and Streptococcus thermophilus, 5 billion CFU) and prebiotic inulin (2.2 g) and tapioca-resistant starch (1.3 g) |
| Total p-cresol (µg/mL) | End of treatment, 0.8 (IQR 0.3–3.7) vs. 3.9 (IQR 3.2–5.8) in synbiotic vs. placebo group (p < 0.05) | |||||||
| Ranganathan et al., 2014 [14] | HD patients HIV, liver disease, drugs or alcohol dependence, anticoagulant therapy, medical debilitating disorder, pregnancy |
n = 22 Age (year) = 54 (29–79) Men (%) = 27 SBP (mmHg) = 148 DBP (mmHg) = 76 |
Probiotics (two capsules /thrice daily) (n = 22) |
Placebo (n = 22) |
Six months | C-reactive protein (mg/L) | No difference between groups | Double blind, crossover Each capsule of probiotic formulation contained 30 billion CFU of S. thermophilus, L. acidophilus and B. longum Six drop-outs; per-protocol analysis performed |
| Total indoxyl glucuronide (mg%) | No difference between groups | |||||||
| QoL-36 score | No difference between groups | |||||||
| Sirich et al., 2014 [15] | HD patients Urea clearance >2 mL/min, active gastrointestinal disease, use of antibiotics within four weeks before study entry |
n = 40 Age (year) = ~56 Men (%) = ~60 HD vintage (year) = ~4 BMI (Kg/m2) = ~29 DM (%) = ~45 |
Prebiotics (resistant starch, up to two sachets/day) (n = 20) |
Placebo (n = 20) |
Six weeks | Urea (mg/dL) | End of treatment, 56 ± 14 vs. 60 ± 19 in prebiotic vs. placebo group (p > 0.05) | Single blind Fiber sachets contained 15 g of high-amylose corn starch (40% digestible and 60% resistant starch); placebo sachets contained 15 g of waxy corn starch Two patients in control group dropped out because of side effects; no side effects in treatment group Sixteen drop-outs (eight in each group; per-protocol analysis performed) |
| C-reactive protein (mg/dL) | End of treatment, 1.1 ± 1.6 vs. 0.8 ± 1.1 in prebiotic vs. placebo group (p > 0.05) | |||||||
| Free indoxyl sulfate (mg/dL) | End of treatment, 0.25 ± 0.17 vs. 0.28 ± 0.15 in prebiotic vs. placebo group (p > 0.05) | |||||||
| Total indoxyl sulfate (mg/dL) | End of treatment, 2.9 ± 1.4 vs. 3.1 ± 1.2 in prebiotic vs. placebo group (p > 0.05) | |||||||
| Free p-cresol (mg/dL) | End of treatment, 0.21 ± 0.14 vs. 0.23 ± 0.14 in prebiotic vs. placebo group (p > 0.05) | |||||||
| Total p-cresol (mg/dL) | End of treatment, 2.9 ± 1.6 vs. 3.1 ± 1.4 in prebiotic vs. placebo group (p > 0.05) | |||||||
| QoL-36 score | No difference between groups | |||||||
| Firouzi et al., 2015 [7] | Type 2 diabetic, mild CKD patients Use of insulin, antibiotics and/or other medication, acute or chronic disease other than DM, hyperlipidemia and hypertension |
n = 136 Age (year) = 53.5 ± 8.5 Men (%) = 52 BMI (kg/m2) = ~29 eGFR (mL/min) = ~74 Urea (mmol/L) = ~4.1 SCr (µmol/L) = ~71 |
Probiotics (60 billion CFU/day) (n = 68) |
Placebo (n = 68) |
12 weeks | eGFR (mL/min) | End of treatment, 73.07 ± 17.13 vs. 68.89 ± 13.55 in probiotic vs. placebo group (p = 0.15) | Double-blind Probiotic supplementation consisted of L. acidophilus, L. casei, L. lactis, Bifidobacterium bifidum, longum and infantis Higher incidence of side effects in probiotic (8.7%) than control group (3.7%) Thirty-five drop outs; (15 in placebo and 20 in probiotic group); ITT and per-protocol analyses performed |
| SCr (µmol/L) | End of treatment, 72.26 ± 19.73 vs. 75.17 ± 18.93 in probiotic vs. placebo group (p = 0.3) | |||||||
| Urea (mmol/L) | End of treatment, 4.04 ± 1.04 vs. 4.24 ± 1.14 in probiotic vs. placebo group (p < 0.05) | |||||||
| Viramontes-Horner et al., 2015 [16] | HD patients, three times/week, for at least three months Current use of probiotics for other reasons, omega-3 fatty acids, pentoxifylline, immunosuppressive and nonsteroidal anti-inflammatory drugs, cancer, HF, chronic liver diseases, intestinal malabsorption and active infection, previous renal transplant |
n = 35 Age (year) = ~40 Men (%) = ~76.5 HD vintage (year) = ~5 BMI (Kg/m2) = ~23.5 DM (%) = ~70 HTN (%) = ~50 SCr (mg/dL) = ~10.5 |
Synbiotics (11 million CFU/day + 2.31g inulin) (n = 20) |
Placebo (n = 15) |
Eight weeks | SCr (mg/dL) | End of treatment, 11.4 (IQR 9.9–13.0) vs. 10.4 (IQR 9.0–13.2) in synbiotic vs. placebo group (p > 0.05) | Double blind Synbiotic formulation consisted of probiotic supplement (L. acidophilus and Bifidobacterium lactis) and prebiotic inulin (2.31 g), omega-3 fatty acids and complex B-vitamins (1.5 g) Patients underwent nutritional counselling consisting of energy (30–35 kcal/kg/day) and protein (1.1–1.2 g/kg/day) intakes and potassium, phosphorus, sodium restriction Seven drop-outs; per-protocol analysis performed |
| Urea (mg/dL) | End of treatment, 148.6 ± 41.6 vs. 131.5 ± 43.8 in synbiotic vs. placebo group (p > 0.05) | |||||||
| C-reactive protein (mg/dL) | End of treatment, 6.3 (IQR 1.8–11.3) vs. 5.0 (IQR 0.6–9.9) in synbiotic vs. placebo group (p > 0.05) | |||||||
| TNF-α (pg/mL) | End of treatment, 2.9 (IQR 0.9–6.7) vs. 3.1 (IQR 0.0–3.7) in synbiotic vs. placebo group (p > 0.05) | |||||||
| IL-6 (pg/mL) | End of treatment, 2.0 (IQR 1.2–3.9) vs. 0.6 (IQR 0.2–3.6) in synbiotic vs. placebo group (p > 0.05) | |||||||
| Nutritional status (SGA) | End of treatment, 1/20 vs. 4/15 had mild to moderate malnutrition in synbiotic vs. placebo group (p > 0.05) End of treatment, 19/20 vs. 11/15 were well nourished in synbiotic vs. placebo group (p > 0.05) |
|||||||
| Wang et al., 2015 [17] | PD patients with eGFR <15 mL/min/1.73 m2 Infectious diseases in the previous month, autoimmune diseases, use of immunosuppressive agents or antibiotics within one month prior to enrollment, pregnancy |
n = 39 Age (year) = ~52 Men (%) = ~46 PD vintage (mo) = ~42 BMI (Kg/m2) = ~23 DM (%) = ~21 HTN (%) = ~81.3 CAD (%) = ~21 SCr (mg/dL) = ~12.5 Urea (mg/dL) = ~58 |
Probiotics (4 billion CFU/day) (n = 21) |
Placebo (n = 18) |
Six months | CrCl (mL/min/1.73 m2) | End of treatment, 1.59 (IQR 0.85–2.93) vs. 1.24 (IQR 0.50–2.74) in probiotic vs. placebo group (p > 0.05) | Double blind One capsule of probiotics consisted of 1 billion CFU per bacterium strain (Bifidobacterium bifidum, catenulatum, longum and L. plantarum) Eight drop-outs; per protocol analysis performed |
| SCr (mg/dL) | End of treatment, 11.76 (IQR 9.55–13.86) vs. 12.84 (IQR 11.84–14.23) in probiotic vs. placebo group (p > 0.05) | |||||||
| Urea (mg/dL) | End of treatment, 57.0 (IQR 50.0–63.0) vs. 55.5 (IQR 48.0–71.0) in probiotic vs. placebo group (p > 0.05) | |||||||
| TNF-α (pg/mL) | End of treatment, 0.74 (IQR 0.41–1.29) vs. 0.74 (IQR 0.18–2.22) in probiotic vs. placebo group (p > 0.05) | |||||||
| IFN-γ (pg/mL) | End of treatment, 7 (IQR 4–12) vs. 8.67 (IQR 2–18.66) in probiotic vs. placebo group (p > 0.05) | |||||||
| IL-5 (pg/mL) | End of treatment, 9.19 (IQR 7.68–12.61) vs. 9.6 (IQR 7.99–12.6) in probiotic vs. placebo group (p > 0.05) | |||||||
| IL-6 (pg/mL) | End of treatment, 1.12 (IQR 0.75–3.93) vs. 0.95 (IQR 0.11–1.7) in probiotic vs. placebo group (p > 0.05) | |||||||
| IL-10 (pg/mL) | End of treatment, 15.97 (IQR 13.47–23.17) vs. 12.69 (IQR 10.25–20.02) in probiotic vs. placebo group (p > 0.05) | |||||||
| IL-17 (pg/mL) | End of treatment, 1.61 (IQR 0.98–2.2) vs. 2.13 (IQR 1.61–3.8) in probiotic vs. placebo group (p > 0.05) | |||||||
| Dehghani et al., 2016 [5] | Stage 3–4 CKD patients HD, use of antibiotics and lactulose two weeks before study entry, alcohol dependence, hepatitis or HIV infection, pregnancy |
n = 66 Age (yr)= 61.0 ± 7.65 Men (%) = 75.8 BMI (Kg/m2) = 28.5 ± 4.1 DM (%) = 98.5 HTN (%) = 84.6 SCr (mg/dL) = ~2.1 eGFR (mL/min/1.73 m2) = ~41.4 Urea (mg/dL) = ~39 |
Synbiotics (two capsules/twice daily) (n = 31) |
Placebo (n = 35) |
Six weeks | Non-fatal CV events | 1/31 vs. 0/35 in synbiotic vs. placebo group (p > 0.05) | Double blind Two capsules (500 mg) of synbiotic supplement consisted of seven strains of probiotics (L. casei, L. acidophilus, L. bulgarigus, L. rhamnosus, Bifidobacterium breve, longum, Streptococcus thermophilus) and prebiotic fructo-oligosaccharides Nine drop-outs; per protocol analysis performed |
| eGFR (mL/min/1.73 m2) | End of treatment, 43.25 ± 17.49 vs. 39.51 ± 17.64 in synbiotic vs. placebo group (p = 0.90) | |||||||
| SCr (mg/dL) | End of treatment, 1.90 ± 0.70 vs. 2.18 ±1 .14 in synbiotic vs. placebo group (p = 0.15) | |||||||
| Urea (mg/dL) | End of treatment, 36.14 ± 20.52 vs. 39.62 ± 27.56 in synbiotic vs. placebo group; p = 0.006 |
|||||||
| Pavan et al., 2016 [18] | Stage 3–5 CKD patients not on dialysis |
n = 24 Age (year) = 57.8 ± 7.11 Men (%) = 66.6 Weight (Kg) = 59.2 ± 8.1 BMI (Kg/m2) = 22±3.2 DM (%) = 62.5 HTN (%) = 16.7 SCr (mg/dL) = 4.4±0.7 |
Synbiotics (three tablets/day) (n = 12) |
Standard therapy (n = 12) |
Six months | eGFR (mL/min/1.73 m2) | GFR declined more rapidly in control than in synbiotic group (−11.6 ± 8.6 vs. −3.4±4.6 per year) (p < 0.001) | Open label One tablet of synbiotic supplementation consisted of 15 billion CFU of each bacterium strain (Streptococcus thermophilus, L. acidophilus and Bifidobacteria longum) and 100 mg of prebiotic fructo-oligosaccharides Patients underwent low protein diet (<0.6 g/kg/day) |
| SCr (mg/dL) | End of treatment, 4.45 ± 0.30 vs. 4.3 ± 0.31 in synbiotic vs. placebo group (p > 0.05) | |||||||
| Poesen et al., 2016 [19] | CKD patients (eGFR 15–45 mL/min/1.73 m2) not on dialysis Gastro-intestinal disease, inflammatory bowel disease, malignancy, previous colorectal surgery and insulin dependent DM, use of antibiotics, prebiotics or probiotics in the previous four weeks before study entry |
n = 40 Age (year) = 70 ± 6 Men (%) = 70 BMI (Kg/m2) = 28.7 ± 5 SCr (mg/dL) = 1.98 (1.60–2.18) eGFR (mL/min/1.73 m2) = 33 (27–38) Proteinuria (g/d) = 0.161 (0.078–0.498) Urea (mg/dL) = 65.5 (51.0–75.5) |
Prebiotics (Arabinoxylan oligo-saccharides 10g/twice daily) (n = 23) |
Placebo (n = 17) |
Four weeks | Urea (mg/dL) | No difference between groups | Double blind, crossover One drop-out (nausea during prebiotic treatment); ITT analysis performed |
| p-cresol (μmol/L) | No difference between groups | |||||||
| p-cresyl glucuronide (μmol/L) | No difference between groups | |||||||
| indoxyl sulfate (μmol/L) | No difference between groups | |||||||
| trimethylamine N-oxide (μmol/L) | Treatment effect (prebiotic vs. placebo) −0.237; 95% CI −0.464, −0.010; p = 0.04) | |||||||
| phenyl-acetyl-glutamine (μmol/L) | No difference between groups | |||||||
| SYNERGY 2016* [20,21,22] | Moderate to severe (pre-HD), hypertensive CKD patients Previous renal transplant, bowel resection or bowel radiation recipient, bowel syndrome, Crohn disease or ulcerative colitis, likely to receive a transplant or progress to dialysis within six months, pre, probiotics or antibiotic use within one month, or change in immunosuppressant dose within six months before study entry |
n = 31 Age (year) = 69 ± 9 Men (%) = 61 BMI (Kg/m2) = 28 ± 6 eGFR (mL/min/1.73 m2) = 25 ± 8 Proteinuria (mg/day) = 296 (168–1100) Albuminuria (mg/day) = 97 (21–677) |
Synbiotic supplements (15 g powder + two capsules/day) (n = 13) |
Placebo (n = 18) |
16 weeks | eGFR (mL/min/1.73 m2) | End of treatment, 24 ± 8 vs. 24 ± 8 in synbiotic vs. placebo group (p = 0.67) | Double blind, crossover Participants underwent a two week run-in period (dietary education with stable protein and fiber intakes) before randomization Synbiotic formulation consisted of 15 g prebiotic (a combination of high–molecular weight inulin, fructo-oligosaccharides and galacto-oligosaccharides) and 90 billion CFU probiotic component (capsule) including nine different strains across the Lactobacillus, Bifidobacteria and Streptococcus genera Six drop-outs; per protocol analysis performed |
| SCr (µmol/L) | End of treatment, 231 ± 75 vs. 233 ± 74 in synbiotic vs. placebo group (p = 0.94) | |||||||
| Proteinuria (mg/day) | End of treatment, 369 (IQR 162–1550) vs. 323 (IQR 169–1150) in synbiotic vs. placebo group (p = 0.20) | |||||||
| Albuminuria (mg/day) | End of treatment, 112 (IQR 16–758) vs. 111 (IQR 12–594) in synbiotic vs. placebo group (p > 0.05) | |||||||
| IL-1β (pg/mL) | End of treatment, 0.8 ± 0.7 vs. 0.8 ± 0.6 in synbiotic vs. placebo group (p = 0.98) | |||||||
| IL-6 (pg/mL) | End of treatment, 2.2 ± 0.9 vs. 2.0 ± 0.8 in synbiotic vs. placebo group (p = 0.40) | |||||||
| IL-10 (pg/mL) | End of treatment, 3.6 ± 2.0 vs. 3.6 ± 2.1 in synbiotic vs. placebo group (p = 0.84) | |||||||
| TNF-α (pg/mL) | End of treatment, 2.2 ± 0.8 vs. 2.0 ± 0.7 in synbiotic vs. placebo group (p = 0.09) | |||||||
| Free indoxyl sulfate (µmol/L) | End of treatment, 0.6 (IQR 0.4–0.8) vs. 0.5 (IQR 0.4–1.0) in synbiotic vs. placebo group (p = 0.20) | |||||||
| Total indoxyl sulfate (µmol/L) | End of treatment, 15 (IQR 10–26) vs. 16 (IQR 12–27) in synbiotic vs. placebo group (p = 0.12) | |||||||
| Free p-cresol (µmol/L) | End of treatment, 2.2 (IQR 0.7–2.8) vs. 2.4 (IQR 1.1–3.4) in synbiotic vs. placebo group (p = 0.34) | |||||||
| Total p-cresol (µmol/L) | End of treatment, 75 (IQR 36–101) vs. 93 (IQR 54–136) in synbiotic vs. placebo group (p = 0.03) | |||||||
| Physical patient-reported health score | End of treatment, 35 ± 11 vs. 37 ± 10 in synbiotic vs. placebo group (p = 0.23) | |||||||
| Mental patient-reported health score | End of treatment, 51 ± 10 vs. 52 ± 9 in synbiotic vs. placebo group (p = 0.75) | |||||||
| Guida et al., 2017 [23] | Kidney transplanted patients with stable graft function Acute rejection or infection in the previous three months, DM, malignancy, pregnancy, food intolerance, autoimmune disorders, severe malnutrition or clinical conditions requiring artificial feeding |
n = 34 Age (year) = ~50.6 Men (%) = ~82.3 Weight (Kg) = ~75.6 WC (cm) = ~94.7 BMI (Kg/m2) = ~25.4 eGFR (mL/min/1.73 m2) = ~54.5 |
Synbiotic supplements (three times/day) (n = 22) |
Placebo (n = 12) |
Four weeks | eGFR (mL/min/1.73 m2) | End of treatment, 53.5 ± 16.0 vs. 57.3 ± 22.1 in synbiotic vs. placebo group (p > 0.05) | Double blind Synbiotic (Probinul Neutro) consisted of probiotic supplement (L. plantarum, 5 billion CFU, L. casei subsp. Rhamnosus, 2 billion CFU, L. gasseri, 2 billion CFU, Bifidobacterium infantis, 1 billion CFU, B. longum, 1 Streptococcus thermophilus, 5 billion CFU) and prebiotic inulin (2.2 g) and tapioca-resistant starch (1.3 g) Two drop-outs; per protocol analysis performed |
| Total p-cresol (µg/mL) | End of treatment, 2.3 (IQR 0.9–2.72) vs. 4.4 (IQR 3.0–6.4) in synbiotic vs. placebo group; p < 0.01 | |||||||
| Miraghajani et al., 2017 [24] | Type 2 diabetic patients with early CKD (proteinuria >300 mg/day and eGFR >90 mL/min) Intolerance to soy milk, smoking, alcoholism, recent antibiotic therapy and use of supplements containing vitamins and minerals, inflammatory bowel disease, infection, liver disease and rheumatoid arthritis |
n = 40 Age (year) = ~55.2 Men (%) = ~47.5 Weight (Kg) = ~71 BMI (Kg/m2) = ~26.5 |
Probiotics (2 billion CFU/day) (n = 20) |
Placebo (n = 20) |
Eight weeks | Progranulin (ng/mL) | End of treatment, 180.90 ± 69.25 vs. 399.56 ± 105.20 in probiotic vs. control group; p = 0.01 | Double blind Participants received individualized dietary counselling (restricted dietary protein, sodium, and potassium intake) before randomization to a diet containing 200 mL/day probiotic soy milk (fortified with 20 million CFU/mL of L. plantarum) or conventional soy milk |
| Soleimani et al., 2017 [6] | Diabetic HD patients, three times/week, for at least one year Intestinal diseases, use of probiotic supplements, prebiotic, antioxidant and anti-inflammatory supplements (vitamin E, C and omega-3 fatty acids), antibiotics and immunosuppressive medications within three months before enrolment, pregnancy |
n = 60 Age (year) = ~56.7 Men (%) = 66.7 Weight (Kg) = ~68.3 BMI (Kg/m2) = ~26.3 HD vintage (year)= ~3.5 HTN (%) = 96.7 SCr (mg/dL) = ~7.6 eGFR (mL/min/1.73 m2) = ~2.35 hs-CRP (ng/mL) = ~7672 Urea (mg/dL) = ~59.2 CVD (%) = ~21.6 CAD (%) = ~78.3 |
Probiotics (6 billion CFU/day) (n = 30) |
Placebo (n = 30) |
12 weeks | eGFR (mL/min/1.73 m2) | End of treatment, 2.54 ± 1.16 vs. 2.25 ± 0.93 in probiotic vs. placebo group (p = 0.77) | Double blind Probiotic supplementation consisted of L. acidophilus, L. casei and Bifidobacterium bifidum, 2 billion CFU/day per strain Five drop-outs; ITT analysis performed |
| SCr (mg/dL) | End of treatment, 7.2 ± 2.6 vs. 7.7 ± 2.9 in probiotic vs. placebo group (p = 0.73) | |||||||
| Urea (mg/dL) | End of treatment, 63.9 ± 26.0 vs. 52.3 ± 12.7 in probiotic vs. placebo group (p = 0.96) | |||||||
| hs-C-reactive protein (ng/mL) | End of treatment, 6110 ± 4812.5 vs. 7555.7 ± 5316.2 in probiotic vs. placebo group; p = 0.03 | |||||||
| Subjective global assessment (SGA) score |
End of treatment, 8.8 ± 2.0 vs. 10.2 ± 3.7 in probiotic vs. placebo group; p = 0.01 | |||||||
| Borges et al., 2018 [25] | HD patients, three times/week, for at least six months Inflammatory and autoimmune diseases, AIDS, cancer, smokers, HD with central catheter access, pregnancy, use of catabolic drugs, antioxidant vitamin supplements, pre-, pro-, synbiotic and antibiotics in the previous three months before study entry |
n = 33 Age (year) = ~52 Men (%) = ~63.6 WC (cm) = ~92 BMI (Kg/m2) = ~25.2 HD vintage (month) = ~48.3 |
Probiotics (90 billion CFU/day) (n = 16) |
Placebo (n = 17) |
12 weeks | SCr (mg/dL) | End of treatment, 9.6 ± 7.7 vs. 10.3 ± 0.6 in probiotic vs. placebo group (p = 0.66) | Double blind Probiotic supplementation consisted of Streptococcus thermophilus, L. acidophilus and Bifidobacteria longum Tirtheen drop-outs; per-protocol analysis performed |
| Urea pre-HD (mg/dL) | End of treatment, 172.6 ± 45.0 vs. 155.9 ± 38.6 in probiotic vs. placebo group (p = 0.37) | |||||||
| Urea post-HD (mg/dL) | End of treatment, 51.3 ± 19.7 vs. 49.5 ± 12.7 in probiotic vs. placebo group (p = 0.54) | |||||||
| C-reactive protein (mg/dL) | End of treatment, 5.5 (95% CI 2.8, 11.7) vs. 1.7 (95% CI 0.8, 6.4) in probiotic vs. placebo group (p = 0.47) | |||||||
| IL-6 (pg/mL) | End of treatment, 38.4 ± 20.1 vs. 30.3 ± 18.5 in probiotic vs. placebo group (p = 0.91) | |||||||
| Total indoxyl sulfate (mg/L) | End of treatment, 36.5 ± 15 vs. 42.5 ± 11.0 in probiotic vs. placebo group (p = 0.60) | |||||||
| Total p-cresol (mg/L) | End of treatment, 46.3 ± 32.7 vs. 57.5 ± 29.8 in probiotic vs. placebo group (p = 0.83) | |||||||
| Total indole-3 acetic-acid (µg/L) | End of treatment, 456.8 ± 199 vs. 744.9 ± 309 in probiotic vs. placebo group (p = 0.45) |
Legend AIDS: acquired immune deficiency syndrome; BMI: body mass index; BUN: blood urea nitrogen; CAD: coronary artery disease; CFU: colony forming units; CI: confidence interval; CKD: chronic kidney disease; CrCl: creatinine clearance; hs-CRP: high sensitive C-reactive protein; CV: cardiovascular; CVD: cardiovascular disease; DBP: diastolic blood pressure; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; HD: hemodialysis; HF: heart failure; HIV: human immunodeficiency virus; HTN: hypertension; IFN: interferon; IL: interleukin; IQR: interquartile range; ITT: intention to treat; PD: peritoneal dialysis; QoL: quality of life; RCT: randomized clinical trial; SBP: systolic blood pressure; SCr: serum creatinine; SGA: subjective global assessment; TNF: tumor necrosis factor; WC: waist circumference; *: main study.