Intestinal microbiota in pediatric patients with end stage renal disease: a Midwest Pediatric Nephrology Consortium study Original paper

What was studied?

This study investigated the intestinal microbiota in pediatric patients with end-stage renal disease (ESRD), focusing on microbiome alterations associated with dialysis modality, renal transplantation, and the generation of bacterially derived uremic toxins. The authors analyzed stool samples using 16S rRNA sequencing and assessed serum levels of p-cresyl sulfate and indoxyl sulfate—key microbially generated solutes. This work directly informs a microbiome signatures database in ESRD, emphasizing shifts in bacterial phyla such as Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, along with specific families including Enterobacteriaceae and Bifidobacteriaceae. The slug and keyphrase “microbiota in pediatric ESRD” capture the heart of this research.

Who was studied?

The study included 39 pediatric participants aged 2–18 years across four groups: hemodialysis (HD), peritoneal dialysis (PD), post-kidney transplant, and healthy controls. Children with comorbidities, recent antibiotic use, or recent transplantation were excluded to reduce confounding factors. This cohort provided a controlled comparison of gut microbial composition, microbial diversity, and toxin accumulation across renal replacement modalities and post-transplant physiology. Demographic and clinical differences—including dialysis duration, eGFR, and BMI—were documented, allowing interpretation of microbial patterns in the context of underlying renal dysfunction.

Most important findings

Children with ESRD exhibited distinct microbiome disruptions. PD patients had a marked reduction in Firmicutes and Actinobacteria, with a significant rise in Proteobacteria—particularly Enterobacteriaceae, as shown in Figures 2 and 5. These shifts align with a dysbiotic pattern characterized by decreased beneficial taxa (e.g., Bifidobacteriaceae) and increased potentially pathogenic taxa. HD patients instead showed elevated Bacteroidetes relative to controls. Alpha diversity was significantly lower in PD and transplant groups, suggesting reduced microbial resilience, while beta diversity analyses (PCoA, page 6) confirmed compositional separation between PD and control microbiota. Serum concentrations of indoxyl sulfate and p-cresyl sulfate were significantly elevated in both ESRD groups, indicating increased microbial toxin production and limited renal clearance. Transplant patients exhibited restored toxin levels but persistent microbial diversity loss, indicating that renal recovery normalizes solute handling but not gut microbial ecology. No correlations were found between microbial diversity and CRP, D-lactate, or toxin concentrations.

Key implications

This study demonstrates that pediatric ESRD is associated with microbiome dysbiosis driven by renal failure and dialysis modality. Microbial signatures—including reduced Firmicutes and Actinobacteria, decreased Bifidobacteriaceae, and expansion of Proteobacteria—serve as potential biomarkers of intestinal barrier disruption and toxin generation. Elevated indoxyl sulfate and p-cresyl sulfate underscore the clinical relevance of microbially derived metabolites in inflammation and cardiovascular risk. The persistent dysbiosis after transplantation suggests that immunosuppression, prior renal disease, or long-standing ecological disruption may hinder microbiome restoration. These findings support integrating microbiome-targeted therapies—dietary fiber, pre/probiotics, or iron-modulation strategies—into pediatric nephrology and provide essential signatures for clinical microbiome databases.

Citation

Crespo-Salgado J, Vehaskari VM, Stewart T, et al. Intestinal microbiota in pediatric patients with end stage renal disease: a Midwest Pediatric Nephrology Consortium study.Microbiome. 2016;4:50. doi:10.1186/s40168-016-0195-9