Molecular characteristics of acute pyelonephritis
Author Information
Author(s): Ambite Ines, Chao Sing Ming, Rosenblad Therese, Hopkins Richard, Storm Petter, Ng Yong Hong, Ganesan Indra, Lindén Magnus, Haq Farhan, Tran Thi Hien, Ahmadi Shahram, Lee Bernett, Chen Swaine L, Godaly Gabriela, Brandström Per, Connolly John E, Svanborg Catharina
Primary Institution: Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Lund University, Lund, Sweden
Hypothesis
This study investigated the molecular basis of disease severity in acute pyelonephritis (APN), a common and potentially life-threatening bacterial infection.
Conclusion
The results define APN as a hyper-inflammatory disorder characterized by a cytokine storm combined with adaptive immune attenuation.
Supporting Evidence
- Acute pyelonephritis is characterized by excessive innate immune activation with a cytokine storm profile.
- Neutrophil degranulation and renal toxicity genes were strongly regulated in the APN group.
- Adaptive immune attenuation was observed in the APN group.
- DNA exome genotyping identified APN and febrile urinary tract infection as genetically distinct.
- The activation of renal toxicity genes during acute infection was unrelated to the development of renal scarring.
- Gene expression analysis revealed a shared molecular basis of disease.
- Neutrophil degranulation was identified as the most strongly activated pathway in febrile UTI and APN.
- Patients with APN showed a specific over-activation profile.
Takeaway
This study found that babies with a serious kidney infection have an overactive immune response that can cause damage, but their ability to fight infections is weakened.
Methodology
Two cohorts of infants with febrile urinary tract infection were included, with molecular disease determinants defined by gene expression analysis and proteomic screens.
Limitations
The study did not find a specific profile of renal toxicity genes associated with renal scarring.
Participant Demographics
Infants and young children with their first febrile urinary tract infection episode.
Statistical Information
P-Value
p<0.001
Confidence Interval
95%
Statistical Significance
p<0.001
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website