Abstract
Synbiotics have emerged as a therapeutic strategy for modulating the gut microbiome and targeting novel cardiovascular risk factors, including uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS). This study aims to evaluate the feasibility of a trial of long-term synbiotic supplementation in adults with stage 3–4 chronic kidney disease (CKD). Adult participants with CKD and estimated glomerular filtration rate (eGFR) of 15–60 mL/min/1.73 m2) were recruited between April 2017 and August 2018 to a feasibility, double-blind, placebo-controlled, randomized trial of synbiotic therapy or matched identical placebo for 12 months. The primary outcomes were recruitment and retention rates as well as acceptability of the intervention. Secondary outcomes were treatment adherence and dietary intake. Exploratory outcomes were evaluation of the cardiovascular structure and function, serum IS and PCS, stool microbiota profile, kidney function, blood pressure, and lipid profile. Of 166 potentially eligible patients, 68 (41%) were recruited into the trial (synbiotic n = 35, placebo n = 33). Synbiotic and placebo groups had acceptable and comparable 12-month retention rates (80% versus 85%, respectively, p = 0.60). Synbiotic supplementation altered the stool microbiome with an enrichment of Bifidobacterium and Blautia spp., resulting in a 3.14 mL/min/1.73 m2 (95% confidence interval (CI), −6.23 to −0.06 mL/min/1.73 m2, p < 0.01) reduction in eGFR and a 20.8 µmol/L (95% CI, 2.97 to 38.5 µmol/L, p < 0.01) increase in serum creatinine concentration. No between-group differences were observed in any of the other secondary or exploratory outcomes. Long-term synbiotic supplementation was feasible and acceptable to patients with CKD, and it modified the gastrointestinal microbiome. However, the reduction in kidney function with synbiotics warrants further investigation.
Highlights
Individuals with chronic kidney disease (CKD) have a significantly increased risk of cardiovascular disease (CVD) and are more likely to die from cardiovascular-related complications than progress to kidney replacement therapy [1]
The uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), have increasingly been associated with accelerated kidney disease progression and cardiovascular morbidity and mortality [3,4,5]. These toxins are produced through the metabolism of the dietary amino acids, tryptophan (IS) and tyrosine (PCS), respectively, by the gut microbiota [6]
Participants were recruited from two kidney care outpatient departments from April 2017 to August 2018 and randomized to synbiotic or placebo group
Summary
Individuals with chronic kidney disease (CKD) have a significantly increased risk of cardiovascular disease (CVD) and are more likely to die from cardiovascular-related complications than progress to kidney replacement therapy [1]. The uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), have increasingly been associated with accelerated kidney disease progression and cardiovascular morbidity and mortality [3,4,5]. These toxins are produced through the metabolism of the dietary amino acids, tryptophan (IS) and tyrosine (PCS), respectively, by the gut microbiota [6]. Both IS and PCS are predominantly bound to plasma proteins, such as albumin, and rely on kidney excretion. An altered gut microbiota and reduced kidney clearance are both contributing factors to increased serum toxin concentrations in CKD [7]
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