Steroid-resistant nephrotic syndrome has a poor prognosis and often leads to end-stage renal disease development. In this issue of the JCI, Ashraf and colleagues used exome sequencing to identify mutations in the aarF domain containing kinase 4 (ADCK4) gene that cause steroid-resistant nephrotic syndrome. Patients with ADCK4 mutations had lower coenzyme Q10 levels, and coenzyme Q10 supplementation ameliorated renal disease in a patient with this particular mutation, suggesting a potential therapy for patients with steroid-resistant nephrotic syndrome with ADCK4 mutations.
The foot processes of WT podocytes are connected by a specialized adherens junction, the slit diaphragm. The complex interaction between podocytes and the glomerular capillaries prevents large molecules like albumin from escaping into Bowman’s capsule. In WT podocytes, ADCK4 (orange ovals) resides in mitochondria and in podocyte foot processes. ADCK4 mutations are associated with foot process effacement and albuminuria (NS). CoQ10 supplementation reversed the phenotypic changes.