Faculty Collaboration Database

The intestinal microbiome of children with initial and recurrent nephrolithiasis: A pilot study and exploratory analysis. J Pediatr Urol 2024 Feb;20(1):18-25

Date

10/07/2023

Pubmed ID

37802717

Pubmed Central ID

PMC10922064

DOI

10.1016/j.jpurol.2023.09.015

Scopus ID

2-s2.0-85173174514 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

INTRODUCTION: Kidney stone disease in children is rising disproportionate to the general population, representing a disease population with a distinct biological mechanism as compared to adults. Factors influencing recurrent kidney stone disease in children are poorly characterized and the associations of the intestinal microbiome within sub-populations of kidney stone formers, however, are not well described. We evaluated a pilot cohort of children with nephrolithiasis comparing patients based on recurrent kidney stone episodes and abnormal 24-h urinary parameters, with dual aims to compare the microbiome signal in children with initial and recurrent nephrolithiasis and to explore additional associations in microbiome composition and diversity within this population.

METHODS: Children aged 6-18 with a history of nephrolithiasis, without an active ureteral calculus or antibiotic exposure within 30 days of study entry were eligible to participate. All participants had a 24-h urine study within 6 months of study entry and provided a fecal sample. Microbiome samples were analyzed using 16S ribosomal DNA sequencing techniques for alpha and beta diversity comparing initial and recurrent stone formers as well as microbiome multivariate association (MaAsLin2) to determine differentially abundant taxa. Shotgun sequencing reads were aligned to custom oxidase degradation and butyrate production gene databases (5 databases total). Comparisons for MaAsLin2 and shotgun metagenomics, normalized to sequencing depth, were based on stone recurrence, sex, hypercalcuria (≤4 mg/kg/day), hyperoxaluria (≥45 mg/1.73 m²), and hypocitraturia (<310 mg/1.73 m² [females] or < 365 mg/1.73 m² [males]).

RESULTS: A total of 16 enrolled children provided samples sufficient for analyses, including 9 girls and 7 boys, of whom 5 had experienced recurrent kidney stone events. Three participants had hypercalcuria, 2 had hyperoxaluria, and 4 had hypocitraturia. Comparisons of Formyl-CoA transferase between index and recurrent urinary stone disease revealed a trend towards higher mean abundance of the gene in initial stone formers (0.166% vs 0.0343%, p = 0.2847) (Summary Figure), while trends toward lower biodiversity were also noted in the recurrent stone cohort on both Faith (p = 0.06) and Shannon (p = 0.05) indices. Exploratory analyses found Eubacterium siraeum to be significantly greater in relative abundance in children with documented hypercalciuria (p = 0.001).

DISCUSSION: Our pilot study demonstrates possible signals in both microbial diversity and oxalate gene expression, both of which are lower in recurrent pediatric kidney stone patients. These findings warrant further investigation as a potential diagnostic marker for future kidney stone events.

Author List

Ellison JS, Atkinson SN, Hayward M, Hokanson E, Sheridan KR, Salzman N

Authors

Samantha N. Atkinson PhD Bioinformatics Analyst III in the Microbiology and Immunology department at Medical College of Wisconsin
Jonathan Scott Ellison MD Associate Professor in the Urologic Surgery department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Child
Female
Gastrointestinal Microbiome
Humans
Hyperoxaluria
Kidney Calculi
Male
Nephrolithiasis
Pilot Projects
Recurrence
Risk Factors
Urolithiasis