Essentials of Diagnosis and General Considerations

• Edema
• Proteinuria >3.5 g/day
• Hypoalbuminemia <3 g/dL
• Hyperlipidemia: cholesterol >300 mg/100 mL
• Lipiduria: free fat, oval fat bodies, fatty casts

Because treatment and prognosis vary with the cause of nephrotic syndrome,  renal biopsy is important.  Light microscopy,  electron microscopy,  and immunofluorescence identification of immune mechanisms diagnose most causes of nephrosis.

Glomerular diseases associated with nephrosis include the following:

Minimal Glomerular Lesions
Minimal-change nephropathy (nil disease)  accounts for about 20% of cases of nephrosis in adults and 90% in children. No abnormality is visible by examination of biopsy material with the light microscope.  With the electron microscope,  alterations of the GBM,  with effacement of foot processes of the epithelial cells, are evident. There is no evidence of immune disease by immunofluorescence studies. The response to treatment with corticosteroids is good,  but for patients who have frequent relapses with steroids or are steroid resistant, a course of cyclophosphamide or chlorambucil may induce a prolonged remission.

Patients who do not respond to these agents may show a favorable response with cyclosporine or tacrolimus. Renal function usually remains stable.

Diagnosis of Medical Renal Disease Medical Renal Disease - History & Examination - Physical Examination - Laboratory Findings - Examination of the Kidneys & Urinary Tract - Renal Biopsy Glomerulonephritis - Poststreptococcal Glomerulonephritis -- General Considerations -- Clinical Findings - IgA Nephropathy - Rapidly Progressive Glomerulonephritis Nephrotic Syndrome - Clinical Findings in Nephrosis - Renal Involvement in Collagen Diseases - Diseases of the Renal Tubules & Interstitium - Hereditary Renal Diseases - Anomalies of the Proximal Tubule - Anomalies of the Distal Tubule

Focal Glomerulosclerosis
Focal glomerulosclerosis is the second most common cause of nephrotic syndrome in children and an increasing cause of the nephrotic syndrome in adults.  The diagnosis is based on light microscope findings of segmental hyalinosis and sclerosis associated with effacement of the foot processes on electron microscopy. Focal glomerulosclerosis is frequently idiopathic but can be associated with human immunodeficiency virus infection and heroin use. A secondary form of focal glomerulosclerosis without the diffuse changes in foot processes may occur in patients with a solitary kidney,  hyperfiltration syndromes,  and reflux nephropathy.  There are reports of familial variants.  The response of the idiopathic form of focal glomerulosclerosis to therapy is suboptimal. Prolonged corticosteroid therapy produces remission in approximately 40%  of patients.

Over a 10-year period, approximately 50% of patients will have chronic renal failure. Idiopathic focal glomerulosclerosis has a recurrence rate of 25% after transplantation.

Membranous Nephropathy
Examination of biopsy material with the light microscope shows thickening of the glomerular cells but no cellular proliferation.  With the electron microscope,  irregular lumpy deposits appear between the basement membrane and the epithelial cells,  and new basement membrane material protrudes from the GBM as spikes or domes.

Immunofluorescence studies show diffuse granular deposits of Ig (especially IgG)  and complement (C3 component). As the membrane thickens, glomeruli become sclerosed and hyalinized.

The pathogenesis of most cases of membranous nephropathy in humans is unclear.  Several mechanisms have been suggested.  They include trapping of circulating immune complexes or binding of an antibody to scattered glomerular antigens (either present already or “planted” after a nonrenal-source antigen lodges in the glomerulus). 

There is considerable controversy regarding the effectiveness of therapy with steroids or immunosuppressive agents. Therapy should be most often used in patients at high risk of progressive renal failure with the following criteria:  proteinuria >5 g/day,  hypertension,  and elevated serum creatinine.