Analysis of Chromosome Abnormalities May Aid Diagnosis of Chronic Kidney Disease in Children

By LabMedica International staff writers
Posted on 04 May 2015

A recent paper discussed the possibility of using a panel of genetic abnormalities to aid in diagnosing children with chronic kidney disease (CKD).

CKD, which initially develops without specific symptoms and is generally only detected as an increase in serum creatinine or protein in the urine, causes serious illness in children, often leading to complications such as high blood pressure, heart disease, neurodevelopmental problems, and behavioral deficits.

Image: Depiction of genomic imbalances detected in patients with chronic kidney disease. The human chromosomes are shown (numbered). The colored bars represent the pathogenic genomic deletions (red) and duplications (blue) detected in a patient. In total, the study identified 21 different genetic lesions in 31 patients, indicating that most patients had a unique genomic pathology. The size of each bar is proportional to the size of the genomic lesion (Photo courtesy of Dr. Ali Gharavi, Columbia University).

Investigators at Columbia University (New York, NY, USA) noted that while there was frequent uncertainty in the identification of specific etiologies of CKD in children, recent studies had indicated that chromosomal microarrays could identify rare genomic imbalances that could clarify the etiology of neurodevelopmental and cardiac disorders in children.

To further elucidate the link between CKD and genomic anomalies, the investigators used Illumina (San Diego, CA, USA) microarrays to genotype 419 children enrolled in the Chronic Kidney Disease in Children (CKiD) Prospective Cohort Study to determine the prevalence of disease-causing copy number variations (CNVs) among various categories of pediatric CKD. The data for the patient population were compared with results obtained by genotyping 21,575 healthy pediatric and adult controls.

Results revealed significant CNVs in 31 (7.4%) of the 419 children with CKD (roughly ten-fold the percentage seen in the controls). The most frequent CNVs were deletions in the HNF1B (hepatocyte nuclear factor 1 homeobox B) gene. The protein encoded by this gene binds to DNA as either a homodimer, or a heterodimer with the related protein hepatocyte nuclear factor 1-alpha. The gene has been shown to function in nephron development, and regulates development of the embryonic pancreas. Mutations that block gene function result in renal cysts, diabetes syndrome, and noninsulin-dependent diabetes mellitus and expression of this gene is altered in some types of cancer.

“With conventional clinical findings, we often cannot determine the exact cause of CKD in children,” said senior author Dr. Ali G. Gharavi, professor of medicine at Columbia University. “However, our study shows that using a readily available genetic screening tool called chromosomal microarray analysis, it is possible in many cases to reach a more precise diagnosis and uncover information that can help define a patient’s risk for other disorders, such as autism or diabetes. Our findings should change clinical practice. Routine genetic screening of kids with CKD would not only improve diagnosis but also help identify those at risk for complications like diabetes and subclinical seizures, which benefit from early detection and treatment.”

The paper was published in the April 20, 2015, online edition of the Journal of Clinical Investigation.

Related Links:

Columbia University
Illumina