Descriptive analysis of gut microbiome alterations in hyperoxaluric patients
Sponsor: Rare Kidney Stone Consortium
Kidney stones are a disease of worldwide prevalence with significant public health implications. About 60–80% of stones are composed of calcium oxalate (CaOx) for which hyperoxaluria is a major risk factor. Idiopathic hyperoxaluria, primary hyperoxaluria and enteric hyperoxaluria are diseases that result in kidney stone formation.
Hypothesis: The diversity and number of microbial populations are different between patients with primary, enteric, idiopathic hyperoxaluria and normal subjects. The expression of bacterial genes involved in oxalate metabolism will be different in hyperoxaluric conditions. At the strain level, we expect a difference in the characteristics of Oxalobacter formigenes (OxF) between normal subjects and patients with primary hyperoxaluria.
Research Design: In a cross-sectional and observational study we will collect stool specimens from subjects with primary hyperoxaluria, idiopathic hyperoxaluria, enteric hyperoxaluria and normal subjects. Each group will include 15 adult subjects.
Primary hyperoxaluria patients will be recruited from the RKSC Primary Hyperoxaluria (PH) registry (Mayo Clinic); enteric hyperoxaluria from the kidney stone clinic at the Mayo Clinic; idiopathic hyperoxaluria patients will be recruited from the kidney stone clinic at New York Harbor Veterans Affairs Medical Center and healthy controls will be recruited from both centers.
Participants: Patients with a diagnosis of idiopathic hyperoxaluria, primary hyperoxaluria, enteric hyperoxaluria and normal subjects with age between 18 and 60 yrs and eGFR>30 ml/min/1.73m2 by MDRD formula. We will exclude participants with history of liver or kidney transplant and any history of antibiotic exposure in the last 6 months.
Analysis: Statistical analysis of microbiome and metagenome composition will be performed in the R statistical programming environment using packages such as ade4, vegan, and phyloseq. Prevalence of OxF and oxalate degradation measurements will be compared between different etiologies of hyperoxaluria and controls using Chi square test and Student’s t test respectively.
Protocol status: pending