What is the role of genetics in the etiology of chronic kidney disease (CKD) in children?

Updated: Jul 21, 2020
  • Author: Sanjeev Gulati, MD, MBBS, DNB(Peds), DM, DNB(Neph), FIPN(Australia), FICN, FRCPC(Canada); Chief Editor: Craig B Langman, MD  more...
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Chronic kidney disease (CKD) is a heterogeneous disease, with possibly both genomic and environmental contributory factors. Various studies have shown a high CKD heritability (30-75%).

Genome-wide association studies (GWAS) and GWAS meta-analyses have identified several genetic loci, including variants in UMOD, SHROOM3, solute carriers, and E3 ubiquitin ligases. However, these genetic markers do not account for all the susceptibility to CKD, and other factors must contribute to the missing heritability.

A shorter telomere length has been associated with renal dysfunction and CKD progression, although most studies include small numbers of cases with variable findings. Copy number variants (CNVs) have been linked to congenital anomalies of the kidney and urinary tract, posterior urethral valves, nephronophthisis, and immunoglobulin A nephropathy. The A3243G mutation in the MT-TL1 gene has been associated with focal segmental glomerulosclerosis.

Only one GWAS has found associations between X chromosome and renal function (rs12845465 and rs5987107). No loci in the Y chromosome have reached genome-wide significance. Although additional biomarkers have been investigated in less common suspects such as telomeres, CNVs, mitochondrial DNA, and sex chromosomes, hidden heritability in CKD remains unexplained. [11]

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