Kidney Week

Abstract: SA-PO606

Urine Microbiota Analysis and mGWAS in Children With Urinary Tract Infections and Vesicoureteral Reflux

Session Information

• Pediatric Nephrology - II
  November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1800 Pediatric Nephrology

Authors

• Verbitsky, Miguel, Columbia University, New York, New York, United States

Miguel Verbitsky,

• Khosla, Pavan, Columbia University, New York, New York, United States

Pavan Khosla,

• Park, Heekuk, Columbia University, New York, New York, United States

Heekuk Park,

• Gupta, Yask, Columbia University, New York, New York, United States

Yask Gupta,

• Khan, Atlas, Columbia University, New York, New York, United States

Atlas Khan,

• Ghavami, Iman, Columbia University, New York, New York, United States

Iman Ghavami,

• Kiryluk, Krzysztof, Columbia University, New York, New York, United States

Krzysztof Kiryluk,

• Sanna-Cherchi, Simone, Columbia University, New York, New York, United States

Simone Sanna-Cherchi,

• Barasch, Jonathan M., Columbia University, New York, New York, United States

Jonathan M. Barasch,

• Mendelsohn, Cathy L., Columbia University, New York, New York, United States

Cathy L. Mendelsohn,

• Uhlemann, Anne-Catrin, Columbia University, New York, New York, United States

Anne-Catrin Uhlemann,

• Gharavi, Ali G., Columbia University, New York, New York, United States

Ali G. Gharavi,

Background

Vesicoureteral reflux (VUR), the retrograde flow of urine from the bladder into the ureters and kidney, accounts for 25-30% of pediatric ESRD worldwide. Urinary tract infections (UTI) are often associated with VUR.

Methods

We performed a microbiota analysis based on 16S rRNA gene sequencing from 325 urine samples of children with urinary tract infections with or without VUR from the RIVUR and CUTIE studies’ cohorts, and a microbiota GWAS (mGWAS) in 278 of them, with genomic DNA available for genotyping.

Results

We found a significant decrease in urine microbiota alpha diversity with VUR (P=3x10^-8), lack of toilet training (P=4x10^-4), and younger age (P=1x10^-3).
Our mGWAS identified genome-wide significant associations with zero-truncated relative abundance of Pseudomonas on chr10 (P=2x10^-9) and Clostridia on Chr3 (P=5x10-8), and a suggestive association with Bacillales (P=3x10^-7) on the same locus as with Pseudomonas. Secondary analysis in female participants showed a suggestive association with Gammaproteobacteria on Chr11 (P=6x10^-8). The top SNPs in these loci were on or near genes associated with immune surveillance, inflammation, and genitourinary tract development and disease (CXCL12, ROBO1, WNT11). We also conducted phenome-wide association studies on the UK Biobank and eMERGE cohorts of the top SNPs showing suggestive associations with UTI and bladder dysfunction.

Conclusion

We report the first combined urine microbiota analysis and mGWAS in children with UTI and VUR, showing associations of bacterial taxa's relative abundances with clinical variables and human host genetic factors.

Funding

• NIDDK Support