Synbiotics Easing Renal Failure by Improving Gut Microbiology II (SYNERGY II): A Feasibility Randomized Controlled Trial
What this study found
Feasibility and acceptability were high: recruitment from eligible patients and 12-month retention were favorable; adherence was high; GI symptoms and stool consistency did not differ between groups. No differences in echocardiographic measures or IS/PCS concentrations. However, synbiotic supplementation reduced eGFR by 3.14 mL/min/1.73 m^2 and increased serum creatinine by 20.8 μmol/L over 12 months (p<0.01); two participants had >40% eGFR decline. No significant changes in stool diversity; modest shifts in gut microbiota and function were observed. Uremic toxins IS and PCS did not change.…
- Study & population
- Double-blind, placebo-controlled randomized trial in adults with CKD stage 3-4; eGFR 15-60 mL/min/1.73 m^2; age ≥18; two tertiary kidney care outpatient departments; 68 randomized; baseline: 66% men; median age 70 (IQR 58-75); median eGFR 34 (IQR 27-41).
- Intervention
- Prebiotic Hi-Maize 260, 20 g/day plus probiotic blend 4.5 × 10^11 CFU/day across nine strains (Lactobacillus acidophilus, L.
- Key limitation
- Small sample size with limited power for secondary outcomes; use of surrogate outcomes; limited generalizability to CKD patients outside eGFR 15–60 mL/min/1.73 m^2; not measuring 24-h urine albumin/proteinuria; single 12-month duration across two sites; metabolomic data not included but suggested for future work.
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Open PDFOriginal 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.