Genetic Test Predicts Therapeutic Response in Pediatric Kidney Disease

Genetic mutations in the kidney’s filtration barrier are frequently linked with a lack of response to immunosuppressive treatments among children with sporadic nephrotic syndrome.

A genetic screening test may help predict which patients with one of the most common childhood kidney diseases will respond to standard therapies and using such a test could help guide clinicians as they counsel and treat patients.


Scientists at the University of Florence (Italy) designed an innovative diagnostic approach that allows for a fast analysis of all genes involved in the disease. The use of this method allowed the team to analyze 46 different genes at the same time in 69 children with the disease, and they found that genetic mutations in the kidney's filtration barrier were frequently linked with a lack of response to immunosuppressive treatments in patients.

DNA was extracted from peripheral blood using a QIAamp DNA Mini Kit (Qiagen; Hilden, Germany) , and the DNA libraries were constructed using Roche NimbleGen (Madison, WI, USA) sample preparation protocol (Rapid Library Preparation Method Manual). A Roche NimbleGen sequence capture array in a solution-based method was used to capture all coding exons and flanking regions of 46 genes. The array included 19 known genes responsible for nephrotic syndrome to potentially identify putative new genes, the other 27 candidate genes associated with proteinuria in animal models and expressed in the glomerular filtration barrier were included.

The innovative strategy allowed the teams to establish the existence of potentially pathogenic variants in 32.3% of 31 patients with sporadic steroid-resistance, whereas using the same technical approach, none of 38 additional patients who exhibited a similar clinical phenotype but were steroid-sensitive had genetic mutations in the analyzed genes. The authors concluded that the results of their study suggest that this type of genetic analysis may improve the approach to children with sporadic nephrotic syndrome by promoting better genetic counseling and management of the treatment.

Paola Romagnani, MD, PhD, the senior author of the study said, “This type of genetic analysis can improve the clinical approach to children with nephrotic syndrome by promoting better genetic counseling for the risk of recurrence of the disease in the family, and a better management of treatment and clinical follow up.” The study was published on July 24, 2014, in the Journal of the American Society of Nephrology.

Related Links:
University of Florence
Qiagen
Roche NimbleGen