A systematic review and meta-analysis pooling 13 randomized clinical trials (511 participants) and 15 controlled rodent studies (312 animals) found that isolated dietary fiber supplementation — predominantly fermentable, non-viscous fibers — significantly reduced circulating indoxyl sulfate (IS) by 0.13 mg/dL in humans and p-cresyl sulfate (pCS) by a borderline-significant 0.23 mg/dL. Animal models showed substantially larger effect sizes for both toxins, alongside increased short-chain fatty acids including cecal acetate and circulating propionate. Longer interventions exceeding 8 weeks showed a trend toward greater pCS reduction.
Indoxyl sulfate and p-cresyl sulfate are protein-bound uremic toxins notoriously difficult to remove via dialysis; their accumulation accelerates cardiovascular disease and renal decline in CKD patients. This meta-analysis adds meaningful quantification to a mechanistically plausible intervention — fiber-driven microbiome shifts that compete with or displace toxin-producing bacterial pathways. The finding that fermentability, rather than viscosity, appears to be the key fiber property is practically useful for dietary guidance in nephrology. However, the low-to-moderate GRADE certainty, notable heterogeneity across studies, and reliance on animal data for SCFA effects temper enthusiasm. Human effect sizes, while statistically significant for IS, are modest. Crucially, this is a preprint posted to medRxiv and has not yet been peer-reviewed — findings and conclusions may be revised. Confirmatory trials with standardized fiber types, longer durations, and hard clinical endpoints like GFR decline are still needed.
