doi:10.1038/nindia.2018.68 Published online 29 May 2018
Researchers have identified novel genetic mutations that cause nephrotic syndrome, a disease in which the kidneys excrete too much protein in urine1.
The researchers also uncover how the genetic mutations disrupt the activity of specific kidney cells that play vital roles in filtering blood and in the formation of urine. These findings may provide new leads for developing therapies for nephrotic syndrome.
Damage to the clusters of small blood vessels in the kidneys that filter waste and excess water from blood usually causes nephrotic syndrome.
Sequencing the genomes of disease-affected people, an international research team – including researchers from Jamia Millia Islamia and All India Institute of Medical Sciences, both in New Delhi, India – zeroed in on six mutated genes. They found that the proteins encoded by such genes interact with one another and regulate the activity of a specific enzyme in podocytes – cells in the kidneys that help flush out toxins from blood.
Silencing the similar genes in mice activated the enzyme in the podocytes, severely disrupting these cells’ functions and hampering the kidneys’ blood-filtering efficiency. However, steroid treatment reduced the activity of the enzyme, indicating that it can act as a potential drug target.
The researchers say that this research sets the stage for revealing specific drug targets in the kidneys, opening new avenues for treating nephrotic syndrome, for which no efficient treatment exists.
1. Ashraf, S. et al. Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment. Nat. Comm. 9, 1960 (2018)