Genetic determinants of renal scarring in children with febrile UTI
Rosenblad, Therese LU ; Lindén, Magnus ; Ambite, Ines LU
; Brandström, Per
; Hansson, Sverker
and Godaly, Gabriela
LU
(2024)
In Pediatric Nephrology
- Abstract
Background: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs. Methods: To assess... (More)
Background: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs. Methods: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy. Results: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes. Conclusions: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs. Graphical abstract: (Figure presented.).
(Less)
- author
- Rosenblad, Therese
LU
; Lindén, Magnus
; Ambite, Ines
LU
; Brandström, Per
; Hansson, Sverker
and Godaly, Gabriela
LU
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- in press
- subject
- keywords
- Genetic polymorphisms, Infants, Long-term consequences, Renal scarring, RS risk factor, Urinary tract infection
- in
- Pediatric Nephrology
- publisher
- Springer
- external identifiers
-
- pmid:38767678
- scopus:85193576916
- ISSN
- 0931-041X
- DOI
- 10.1007/s00467-024-06394-6
- language
- English
- LU publication?
- yes
- id
- 6b74a5f4-e791-48fa-8f16-78f6fbc5787e
- date added to LUP
- 2024-06-13 14:58:50
- date last changed
- 2024-06-14 03:00:27
@article{6b74a5f4-e791-48fa-8f16-78f6fbc5787e,
abstract = {{<p>Background: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs. Methods: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy. Results: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes. Conclusions: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs. Graphical abstract: (Figure presented.).</p>}},
author = {{Rosenblad, Therese and Lindén, Magnus and Ambite, Ines and Brandström, Per and Hansson, Sverker and Godaly, Gabriela}},
issn = {{0931-041X}},
keywords = {{Genetic polymorphisms; Infants; Long-term consequences; Renal scarring; RS risk factor; Urinary tract infection}},
language = {{eng}},
publisher = {{Springer}},
series = {{Pediatric Nephrology}},
title = {{Genetic determinants of renal scarring in children with febrile UTI}},
url = {{http://dx.doi.org/10.1007/s00467-024-06394-6}},
doi = {{10.1007/s00467-024-06394-6}},
year = {{2024}},
}