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Genetic determinants of renal scarring in children with febrile UTI
Therese Rosenblad1, Magnus Lindén2, Ines Ambite3
1Section for Pediatric Nephrology, Skåne University Hospital, Lund, Sweden.
Insights
Infant febrile urinary tract infections (UTIs) can lead to kidney damage. Genetic analysis identified mitochondrial gene variations as key predictors of renal scarring (RS) and recurrent UTIs in infants.
Area of Science:
- Genetics
- Pediatrics
- Infectious Diseases
Background:
- Febrile urinary tract infections (UTIs) are severe infant infections with potential complications.
- Identifying infants at risk for recurrent UTIs or kidney damage is clinically challenging.
- Genetic factors may influence UTI outcomes and disease severity.
Purpose of the Study:
- To identify genetic susceptibility variants for renal scarring (RS) after infant UTIs.
- To find genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs.
- To develop an infection management strategy based on individual genetic risk.
Main Methods:
- Exome genotyping of DNA from infant blood samples.
- Bioinformatics analysis including allelic frequency tests and odds ratio calculations.
- Kidney involvement assessed by dimercaptosuccinic acid (DMSA) scintigraphy.
Main Results:
- A cohort of 1087 infants with first febrile UTI was analyzed.
- Gene association analysis in 137 infants with DMSA scans revealed genetic distinctions.
- Mitochondrial genes were prominently featured in the genetic signature of infants with renal scarring.
Conclusions:
- Mitochondrial gene polymorphisms are key genetic susceptibility factors for renal scarring (RS) post-febrile UTI in infants.
- This genetic profile can predict future complications like RS and recurrent UTIs.
- Genetic risk stratification may aid in managing infant UTIs.
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.
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