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J Pediatr Genet 2016; 05(01): 043-050
DOI: 10.1055/s-0035-1557111
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Genetic Considerations in Pediatric Chronic Kidney Disease

Lyndsay A. Harshman
1   Division of Pediatric Nephrology, Stead Family Department of Pediatrics, University of Iowa Children's Hospital, Iowa City, Iowa, United States
,
Diana Zepeda-Orozco
1   Division of Pediatric Nephrology, Stead Family Department of Pediatrics, University of Iowa Children's Hospital, Iowa City, Iowa, United States
› Author Affiliations
Further Information

Publication History

20 January 2015

27 February 2015

Publication Date:
13 August 2015 (online)

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Abstract

Chronic kidney disease (CKD) in children is an irreversible process that, in some cases, may lead to end-stage renal disease. The majority of children with CKD have a congenital disorder of the kidney or urological tract arising from birth. There is strong evidence for both a genetic and epigenetic component to progression of CKD. Utilization of gene-mapping strategies, ranging from genome-wide association studies to single-nucleotide polymorphism analysis, serves to identify potential genetic variants that may lend to disease variation. Genome-wide association studies evaluating population-based data have identified different loci associated with CKD progression. Analysis of single-nucleotide polymorphisms on an individual level suggests that secondary systemic sequelae of CKD are closely related to dysfunction of the cardiovascular-inflammatory axis and may lead to advanced cardiovascular disease through abnormal vascular calcification and activation of the renin–angiotensin system. Similarly, genetic variants affecting cytokine control, fibrosis, and parenchymal development may modulate CKD through development and acceleration of renal interstitial fibrosis. Epigenetic studies evaluate modification of the genome through DNA methylation, histone modification, or RNA interference, which may be directly influenced by external or environmental factors directing genomic expression. Lastly, improved understanding of the genetic and epigenetic contribution to CKD progression may allow providers to identify a population at accelerated risk for disease progression and apply novel therapies targeted at the genetic mechanism of disease.

Keywords

pediatric chronic kidney disease - epigenetic modifications - single-nucleotide polymorphisms
 

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