Identification of a genetic mutation associated with steroid-resistant nephritic syndrome
Patients with nephritic syndrome exhibit an array of symptoms that are associated with loss of kidney function, including excess protein in urine, swelling, and albuminuria. Many nephritic syndrome patients respond well to treatment with steroids; however, subsets of patients are resistant to steroid treatment and are at high risk of kidney failure. Recent studies have identified single gene mutations that are associated with development of steroid-resistant nephritic syndrome; however, these mutations account for approximately half of all steroid-resistant cases.
In this issue of the Journal of Clinical Investigation, Friedhelm Hildebrandt and colleagues at Boston Children's Hospital identified mutations in gene encoding the aarF domain containing kinase 4 (ADCK4) in 15 individuals with steroid-resistant nephritic syndrome from 8 different families.
The authors found that cells isolated from patients with ADCK4 mutations had reduced levels of coenzyme Q1 (CoQ10), and decreased mitochondrial respiration.
Furthermore, one patient with ACDK4-assocatiated steroid-resistant nephritic syndrome showed improvement following treatment with CoQ10.
In their companion commentary, Laura Malaga-Dieguez and Katalin Susztak of the University of Pennsylvania suggest that CoQ10 treatment may be promising for a subset of patients with steroid-resistant nephritic syndrome.
ADCK4 "reenergizes" nephrotic syndrome, J Clin Invest. 2013;123(12):4996–4999. DOI: 10.1172/JCI73168