Excerpt from Nephrotic Syndrome

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Background: The term nephrosis, or nephrotic syndrome, had its origin in the early 20th century and was introduced primarily to distinguish it from nephritis, a label used to denote a clinical state associated with hematuria, proteinuria, and a cellular proliferation of the glomerulus. It describes a clinical condition of edema and proteinuria in which the renal histology (light microscopy) demonstrates fatty degeneration of the tubules associated with normal appearing glomeruli. Briefly, the name was modified to lipoid nephrosis after the routine finding of lipid droplets in the urine of affected patients.

The nephrotic syndrome (NS) is a clinical entity characterized by massive loss of urinary protein (primarily albuminuria) leading to hypoproteinemia (hypoalbuminemia) and its result, edema. Hyperlipidemia, hypercholesterolemia, and increased lipiduria are usually associated. Although not commonly thought of as part of the syndrome, hypertension, hematuria, and azotemia may occur. NS generally has a glomerular cause and is currently categorized into primary and secondary forms. The name primary NS (PNS) has replaced, in some circles, the older designation of idiopathic NS (INS), but both terms denote a similar same vagueness as to cause. Included are a variety of clinical as well as pathologic states. The term secondary NS relates to the clinical state associated with other, more clearly defined diseases such as anaphylactoid purpura, systemic lupus erythematosus, diabetes mellitus, sickle cell disease, syphilis, and others. In the following sections, the majority of attention will be devoted to PNS or INS because of the relative frequency in children.

The subcategories of PNS are based on histologic descriptions, but clinical-pathological correlations have been made. Even though knowledge of specific causes of NS are too limited for more precise classification, the variants of PNS/INS will be considered as clinical disease states with well-defined histopathologic processes. The histologic type at onset makes it possible to generalize about such things as response to therapy and ultimate prognosis. When possible, the authors use the definitions, descriptions, and nomenclature developed by the International Study of Kidney Diseases in Children (ISKDC). Most attention will be devoted to minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) with only modest attention to familial or congenital nephrosis, membranoproliferative glomerulonephritis (MPGN), and membranous glomerulonephritis (MGN).

The overall prevalence of NS in childhood is approximately 2-5 cases per 100,000 children. The cumulative prevalence rate is approximately 15.5/100,000. MCNS is the most common form in children, and its prevalence is inversely proportional to the age at onset (ie, the younger the child, the more likely the histology will show minimal abnormalities on light microscopic evaluation of glomerular histology). Histologic variations exist within this category in which some patients demonstrate only fusion and smudging of the epithelial cell podocytes while others may demonstrate mild changes within the glomerular mesangium consisting of either proliferation or sclerosis. Since patients with MCNS have the highest rate of responsiveness to standard therapy and the best long-term prognosis, the separation of MCNS from others is important.

IgM mesangial nephropathy (IgM nephropathy) may be a separate entity from MCNS. Assignment of type of NS by histologic criteria is based predominately on light microscopic findings. Most patients with isolated IgM mesangial immunofluorescent staining present clinical characteristics similar to those with MCNS. Whether the finding of immune deposits of IgM alters either response to therapy or subsequent course is controversial.

Focal segmental glomerulosclerosis (FSGS) is the second most common histologic subtype seen i .....