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2016 ; 5
(1
): 43-50
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Genetic Considerations in Pediatric Chronic Kidney Disease
#MMPMID27617141
Harshman LA
; Zepeda-Orozco D
J Pediatr Genet
2016[Mar]; 5
(1
): 43-50
PMID27617141
show ga
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.