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.

^aComposite of dialysis initiation, kidney transplant, and serum creatinine doubling.