Pediatric Nephrology

, Volume 26, Issue 7, pp 1017–1029 | Cite as

Genetic susceptibility to renal scar formation after urinary tract infection: a systematic review and meta-analysis of candidate gene polymorphisms

  • Marco ZaffanelloEmail author
  • Stefano Tardivo
  • Luigi Cataldi
  • Vassilios Fanos
  • Paolo Biban
  • Giovanni Malerba


Identifying patients who may develop renal scarring after urinary tract infections (UTI) remains challenging, as clinical determinants explain only a portion of individual risk. An additional factor that likely affects risk is individual genetic variability. We searched for peer-reviewed articles from 1980 to December 2009 in electronic databases that reported results showing an association between gene polymorphims and renal scaring after UTI. Two independent researchers screened articles using predetermined criteria. Studies were assessed for methodological quality using an aggregate scoring system. The 18 studies ultimately included in the review had investigated 16 polymorphisms in nine genes in association with renal scarring formation after UTI. Based on the predetermined criteria for assessing the quality of the studies, 12 studies (67%) were identified as being of poor quality design. A meta-analysis of cumulative studies showed on association between renal scarring formation after UTI and the angiotensin converting enzyme insertion/deletion polymorphism [ACE I/D; recessive model for D allele; odds ratio (OR) 1.73, 95% confidence interval (CI) 1.09–2.74, P = 0.02] or transforming growth factor (TGF)-β1 c.-509 T > C polymorphism (dominant model for T allele; OR 2.24, 95% CI 1.34–3.76, P = 0.002). However, heterogeneity among studies was large, indicating a strong difference that cannot only be explained by differences in study design. The studies reviewed in this article support a modest involvement of the vasomotor and inflammatory genes in the development of renal scarring after UTIs. This review also shows that only few possible candidate genes have been investigated for an association with renal scarring, raising the hypothesis that some gene polymorphisms may exert their effects through an interaction with as yet uninvestigated factors that may be related to geographic and/or socio-economic differences.


Urinary tract infection Genetic polymorphism Renal scarring Vesicoureteral reflux Systematic review 


Declarations of competing interest



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Copyright information

© IPNA 2010

Authors and Affiliations

  • Marco Zaffanello
    • 1
    • 7
    Email author
  • Stefano Tardivo
    • 2
  • Luigi Cataldi
    • 3
  • Vassilios Fanos
    • 4
  • Paolo Biban
    • 5
  • Giovanni Malerba
    • 6
  1. 1.Department of Life and Reproduction Sciences, Section of PediatricsUniversity of VeronaVeronaItaly
  2. 2.Department of Medicine and Public Health, Section of Hygiene and Preventive, Environmental and Occupational MedicineUniversity of VeronaVeronaItaly
  3. 3.Division of NeonatologyCatholic University of Sacred HeartRomeItaly
  4. 4.Neonatal Intensive Care UnitUniversity of CagliariCagliariItaly
  5. 5.Neonatal and Paediatric Intensive Care Unit, Division of PaediatricsMajor City HospitalVeronaItaly
  6. 6.Department of Life and Reproduction Sciences, Section of Biology and GeneticsUniversity of VeronaVeronaItaly
  7. 7.Department of Life and Reproduction SciencesUniversity of VeronaVeronaItaly

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