Porth's Essentials of Pathophysiology, 4e

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Disorders of Renal Function

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disease (lipoid nephrosis), focal segmental glomerulo- sclerosis, and membranous glomerulonephritis. The rela- tive frequency of these causes varies with age. In children younger than 15 years of age, nephrotic syndrome almost always is caused by primary idiopathic glomerular dis- ease, whereas in adults it often is a secondary disorder. 4 Minimal-Change Disease (Lipoid Nephrosis). Minimal- change disease is characterized by diffuse loss (through fusion) of the podocytes or foot processes of the visceral epithelial cells of the glomeruli. It is most commonly seen in children (peak incidence at 2 to 6 years of age), 5 but may occasionally occur in adults. Although the cause of minimal-change disease is unknown; children in whom the disease develops often have a history of recent upper respiratory infections or of receiving routine childhood immunizations. 4 Minimal-change disease does not usu- ally progress to renal failure, but can cause significant complications, including predisposition to infection with gram-positive organisms, tendency toward throm- boembolic events, hyperlipidemia, and protein malnu- trition. The prognosis in children with the disorder is good; more than 90% respond to a short course of glu- cocorticoids. Adults also respond to corticosteroids, but the response is slower. 4 Membranous Glomerulonephritis. Membranous glo- merulonephritis is the most common cause of primary nephrosis in adults. 5,10,11 The disorder is caused by diffuse thickening of the glomerular basement membrane due to deposition of immune complexes. The disorder may be idiopathic or associated with a number of disorders, including autoimmune diseases such as SLE, infections such as chronic hepatitis B, metabolic disorders such as diabetes mellitus and thyroiditis, and use of certain drugs such as gold compounds, penicillamine, and captopril. 5 The disorder usually begins with an insidious onset of the nephrotic syndrome with peripheral edema, hypoalbuminemia, and hyperlipidemia or, in a small percentage of patients, with nonnephrotic proteinuria. Hematuria and mild hypertension may be present. The progress of the disease is variable, with less than 40% eventually developing renal insufficiency. Spontaneous remissions and a relatively benign outcome occur more commonly in women and those with proteinuria in the nonnephrotic range. Treatment is controversial. Because of the variable course of the disease, the overall effec- tiveness of corticosteroids and other immunosuppres- sive therapy in controlling the progress of the disease has been difficult to evaluate. 5,10 Focal Segmental Glomerulosclerosis. Focal segmen- tal glomerulosclerosis (FSGS) is characterized by scle- rosis (i.e., increased collagen deposition) in some but not all glomeruli. Moreover, in the affected glomeruli, only a portion of the glomerular tuft is involved. 4,5,10,11,15 Focal segmental glomerulosclerosis causes 30% of pri- mary nephrotic syndrome in adults and 10% in chil- dren. It is more common in blacks than whites and is the leading cause of primary nephrotic syndrome in African Americans. 5

The largest proportion of protein lost in the urine is albumin, but globulins also may be lost. As a result, persons with nephrosis are often vulnerable to infec- tions, particularly those caused by staphylococci and pneumococci. 4 This decreased resistance to infection probably is related to the loss of both immunoglobulins and low–molecular-weight complement components in the urine. Many binding proteins also are lost in the urine. Consequently, the plasma levels of many ions (iron, copper, zinc) and hormones (thyroid and sex hor- mones) may be low. Many drugs require protein binding for transport. Hypoalbuminemia reduces the number of available protein-binding sites, thereby producing a potential increase in the amount of free (active) drug that is available. Persons with nephrotic syndrome are also at risk for thrombotic complications. These complications reflect a disruption in the function of the coagulation system brought about by a loss of coagulation and anticoagula- tion factors in the urine. Renal vein thrombosis, once thought to be a cause of the disorder, is more likely a consequence of the hypercoagulable state. Other throm- botic complications include deep vein thrombosis and pulmonary emboli. The glomerular derangements that occur with nephro- sis can develop as a primary disorder or secondary to changes caused by systemic diseases such as diabe- tes mellitus and SLE. 4,5 Among the primary glomerular lesions leading to nephrotic syndrome are minimal-change FIGURE 25-9. Photo of an African child with nephrosis associated with malaria. (From the Centers for Disease Control and Prevention Public Health Images Library. No. 3894. Courtesy of Myron Schultz.)