Table 2.
Therapies that modify the human intestinal microbiome and bacterial byproduct metabolism in kidney disease
Study Design | Intervention | Subjects | Primary Outcome | Secondary Outcomes | Ref. |
---|---|---|---|---|---|
Adsorbent | |||||
RCT, 1:1 active versus placebo, 189-wk EPPIC1, 170-wk EPPIC2 | AST-120 | CKD 4, n=2035 | No change in time to kidney disease progressiona | No change in time to kidney disease progression,a including death | 40 |
Synbiotic | |||||
RCT, 2:1 active versus placebo, 30 d | Probinul Neutra | After kidney transplant, n=36 | ↓ p-Cresol | No change in kidney function, glycemia, lipids, albumin | 41 |
RCT, active versus placebo, 6-wk crossover, 4-wk washout | Synbiotic | CKD 3–4, n=37 | No change in indoxyl sulfate | ↓ p-Cresol; significant change in microbiome; ↑ albuminuria; no change in eGFR, urinary kidney injury molecule-1, serum inflammatory, or oxidative stress biomarkers | 42 |
RCT, 1:1 active versus placebo, 30 d | Probinul Neutra | CKD 3–4, n=30 | ↓ p-Cresol | No change in gastrointestinal symptoms | 43 |
RCT, 1:1 active versus placebo, 2 mo | Synbiotic | ESKD, n=18 | ↑ Stool bifidobacterial counts | ↓ Gastrointestinal symptoms | 44 |
RCT, 1:1 active versus placebo, 2 mo | Synbiotic | ESKD, n=44 | ↓ Gastrointestinal symptoms | ↓ Markers of malnutrition and serum CRP and TNF-α levels (NS) | 45 |
Prebiotic | |||||
RCT, active versus placebo, 6-wk crossover, 4-wk washout | Arabinoxylan oligosaccharides | CKD 3–4, n=39 | ↓ TMAO; no change in urea, p-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate, phenylacetylglutamine | No change in urinary excretion of urea, p-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate, phenylacetylglutamine, TMAO; no change in insulin resistance | 46 |
Sevelamer | |||||
RCT, 1:1 active versus placebo, 3 mo | Sevelamer | CKD 3–5 (predialysis), n=69 | ↓ p-Cresol | ↓ LDL and serum phosphorus | 8 |
Dietary fiber | |||||
Single blinding, 12 wk | Dietary fiber | CKD 3, n=13 | ↓ p-Cresol | ↑ Stool frequency; no change in quality of life | 47 |
RCT, 1:1 active versus placebo, 6 wk | Dietary fiber | ESKD, n=40 | ↓ Indoxyl sulfate; ↓ p-cresol (NS) | No change in predialysis weight, BUN, serum albumin, prealbumin, CRP, phosphorus, or KDQOL-36 | 48 |
Antibiotics | |||||
Observational, 28 d | Single 250-mg oral dose of vancomycin | ESKD, n=10 | ↓ Indoxyl sulfate; ↓ p-cresyl sulfate | Decrease in gut microbiome diversity | 9 |
RCT, randomized, controlled trial; EPPIC1, Evaluating Prevention of Progression of CKD 1; EPPIC2, Evaluating Prevention of Progression of CKD 2; CRP, C-reactive protein; NS, nonsignificant; TMAO, trimethylamine-N-oxide; KDQOL-36, Kidney Disease Quality of Life 36 instrument.
Composite of dialysis initiation, kidney transplant, and serum creatinine doubling.