Nephrotic syndrome is one of the most common renal diseases in childhood. In recent estimates, idiopathic nephrotic syndrome, the most common type, occurs in about 16 per 100,000 children.1 Nephrotic syndrome is caused by problems with the selective permeability of the glomerular filtration system. It is diagnosed by four key clinical features: proteinuria, hypoalbuminemia, edema, and hyperlipidemia. The most common types of childhood nephrotic syndrome are responsive to steroids and can be managed on an outpatient basis.
Nephrotic syndrome can be classified in several ways, including histopathology, inclusion/exclusion of systemic disease, and response to steroids. The disease can be divided into three major categories—primary nephrotic syndrome, secondary nephrotic syndrome, and congenital/infantile nephrotic syndrome. The most common form in childhood is primary idiopathic nephrotic syndrome (Table 115-1). In secondary nephrotic syndrome, the disease may have similar histology as primary forms; however, the disease stems from a systemic, rather than nephrogenic, illness. The essential element in all types of nephrotic syndrome is an abnormal selectivity of the permeable barrier, which leads to pathologic protein loss across the glomerular basement membrane (GBM) (Figure 115-1). The endothelial cells on the GBM are normally negatively charged and serve as a barrier to large anions such as albumin from leaking out into the urine. In minimal change disease (MCD), the most common type of idiopathic nephrotic syndrome, this anionic charge is lost secondary to structural damage to the epithelium; as a result, increased amounts of albumin cross into the urine. The foot processes and slit pores on the other side of the GBM serve as size barrier. In other types of nephrotic syndrome, large neutral proteins such as IgG inappropriately cross the filtration system and spill into the urine.
TABLE 115-1Classification of Nephrotic Syndrome |Favorite Table|Download (.pdf) TABLE 115-1 Classification of Nephrotic Syndrome
Primary nephrotic syndrome = no systematic disease
Secondary nephrotic syndrome = systematic disease
Congenital/infantile nephrotic syndrome = classified based on gene mutations
Mutation of NPHS1, which encodes nephrin
Mutation of NPHS2, which encodes podocin
Denys-Drash syndrome: mutation of WT1, which encodes transcription tumor suppressor
Pierson syndrome: mutation of LAMB2, which encodes laminin β1
Diffuse mesangial sclerosis: mutation of PLCE1, which encodes phospholipase C epsilon