Nephrotic Syndrome

63 Nephrotic Syndrome



Nephrotic syndrome is defined by an association of the following four clinical and laboratory findings: (1) edema, (2) proteinuria, (3) hypoalbuminemia, and (4) hyperlipidemia. Nephrotic syndrome may be a manifestation of many underlying renal disease processes. Most often in children, however, the nephrotic syndrome is idiopathic, with an incidence of two to seven per 100,000 children younger than 16 years old. Idiopathic nephrotic syndrome can be broadly categorized based on the response to oral steroid treatment (steroid sensitive, steroid dependent, and steroid resistant). The majority of biopsy specimens comprise three underlying histologic lesions: minimal-change nephrotic syndrome (MCNS), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy, the latter being rare in childhood. MCNS is the most common (60%-90% of cases), although there has been an apparent increase in the incidence of FSGS over the past several decades.



Etiology and Pathogenesis


Although most often idiopathic, a variety of conditions and agents are associated with the nephrotic syndrome. These include (1) infections (e.g., HIV, hepatitis B and C, syphilis, toxoplasmosis, malaria), (2) drugs or toxins (e.g., nonsteroidal antiinflammatory drugs, lithium, ampicillin, penicillamine, heroin, mercury), (3) malignancy (lymphoma, leukemia), (4) allergens (e.g., certain foods and bee stings), and (5) obesity. Nephrotic syndrome may also be an associated feature of several glomerulonephritides, such as lupus nephritis, membranoproliferative glomerulonephritis (MPGN), and immunoglobulin A (IgA) nephropathy. With advances in molecular biology, there has been increasing discovery of genetic disorders resulting in steroid-resistant nephrotic syndrome (Table 63-1). The clinical course and histopathology depend on the underlying disease process or precipitating factors.



The frequent association of both the onset and relapse of “idiopathic” nephrotic syndrome with an antecedent upper respiratory tract infection or atopic event, as well as the response to immunosuppressive therapy, suggests that it is immunologically mediated. Multiple immunologic abnormalities and circulating factors that affect glomerular capillary permeability have been described, but the exact pathophysiology remains to be elucidated. The established familial occurrence (mostly in siblings) and similarity of the clinical course within families also implicate genetic factors.


Although the pathophysiologic mechanisms responsible for nephrotic syndrome clearly involve both environmental and genetic factors and differ based on the underlying diagnosis, the unifying pathology is damage to the glomerular filtration barrier either through injury to the glomerular basement membrane (GBM) or podocytes. On electron microscopy, there is effacement, retraction, and vacuolization of epithelial foot processes, and in the unique case of membranous nephropathy, there are immune complex deposits. Light microscopy may show no abnormalities (minimal change), mesangial proliferation or matrix expansion, any of several morphologic variants of focal and segmental glomerulosclerosis (FSGS), or thickening of the GBM (membranous). Immunofluorescent staining results are typically negative in MCNS. There are characteristic patterns of staining in FSGS and membranous nephropathy as well as in the primary glomerulonephritides associated with nephrotic syndrome, such as lupus and MPGN (Figure 63-1). Although the histopathology is important, particularly if there is significant tubulointerstitial fibrosis and glomerulosclerosis, the response to steroid therapy is the most important predictor of clinical outcome.




Clinical Presentation



Stay updated, free articles. Join our Telegram channel

Jun 19, 2016 | Posted by in PEDIATRICS | Comments Off on Nephrotic Syndrome

Full access? Get Clinical Tree

Get Clinical Tree app for offline access