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.

PATHOPHYSIOLOGY

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.

A common presentation of nephrotic syndrome is a young child who has edema, often periorbital, following an upper respiratory illness. This is may be initially diagnosed as an allergic reaction, but the edema eventually becomes more generalized, leading to the correct diagnosis. The edema in nephrotic syndrome is gravity dependent and may therefore be present in the lower extremities, back/sacral area, and genital area; the edema is often soft and pitting. Extreme edema may lead to anasarca and ascites. Edema is caused by sodium retention from kidney disease and low plasma oncotic pressure. It is important to note that while the extravascular space is fluid overloaded (“third spacing”), there is intravascular volume contraction. As a result, some children may present with tachycardia, oliguria, hypotension, or shock.^1-3

The differential diagnosis for edema is large and includes non-renal disease (such as protein-losing enteropathy and congestive heart failure) and primary and secondary nephrotic syndrome (Table 115-2 and Figure 115-2). The causes of edema can be categorized based on changes in pressure. If there is increased capillary hydrostatic pressure, decreased capillary oncotic pressure, increased interstitial hydrostatic pressure, or increased capillary permeability, a child will develop edema. What distinguishes nephrotic syndrome from other diagnoses is identification of laboratory findings.