The majority of children who present with idiopathic nephrotic syndrome (NS) have minimal change disease (MCD), which is generally responsive to steroid therapy. As a result, empirical steroid therapy is given to most children who present with idiopathic NS.
However, about 10 to 20 percent of patients will fail to respond to initial steroid treatment. In many cases, steroid-resistant cases are due to single gene mutations that affect glomerular podocyte differentiation and function. Patients with genetic forms of steroid-resistant nephrotic syndrome (SRNS) are usually unresponsive to immunosuppressive therapy. Thus, therapeutic decisions in children with SRNS are based on the underlying etiology.
The causes and management of steroid-resistant idiopathic nephrotic syndrome in children will be reviewed here. The etiology, clinical manifestations, diagnosis, and initial management of NS in children are discussed separately. In addition, the management of children with steroid-sensitive NS is presented elsewhere. (See "Etiology, clinical manifestations, and diagnosis of nephrotic syndrome in children" and "Treatment of idiopathic nephrotic syndrome in children", section on 'Initial pharmacologic therapy' and "Treatment of idiopathic nephrotic syndrome in children", section on 'Steroid-sensitive nephrotic syndrome'.)
In most children with steroid-resistant nephrotic syndrome (SRNS), the underlying cause is not known [1,2]. However, advances in molecular genetics of glomerular diseases have shown single gene defects that affect glomerular podocyte differentiation and function are responsible for a quarter to a third of all pediatric cases of SRNS in many parts of the world [3-5].
Genetic mutations — Mutations of the following genes are the most common cause of hereditary SRNS.