Primary Glomerulopathies (Nephrotic)

PRIMARY GLOMERULOPATHIES (NEPHROTIC)

Membranous glomerulonephritis is a common cause of nephrotic syndrome in adults that is mediated by immune complexes.

Most cases (85%) are idiopathic; in most of these cases, autoantibodies cross-react with podocyte antigens. Membranous glomerulonephritis may also be caused by drugs (penicillamine), infections (hepatitis virus B and C, syphilis, etc.), and systemic diseases (SLE, diabetes mellitus, etc.). It has also been associated with malignant car-cinomas of the lung and colon, and there may be a genetic predisposition.

Renal biopsy shows diffuse thickening of the capillary walls. Basement membrane projections (“spikes”) are seen on silver stains. Immunofluorescence shows a gran-ular and linear pattern of IgG and C3. Electron microscopy shows subepithelial deposits along the basement membranes with effacement of podocyte foot processes.

The clinical course is variable and may lead to spontaneous remission, persistent proteinuria, or end-stage renal disease.

Minimal change disease (also called lipoid nephrosis and nil disease) is the most common cause of nephrotic syndrome in children. Peak incidence is age 2–6.

The diagnosis is one of exclusion. Light microscopy shows normal glomeruli with lipid accumulation in proximal tubule cells (lipoid nephrosis). Immunofluorescence is negative, with no immune deposits. Electron microscopy shows effacement of epithelial (podocyte) foot processes, microvillous transformation, and no immune complex deposits.

The prognosis is excellent because treatment with corticosteroids produces a dra-matic response in children. The majority have a complete recovery.

Focal segmental glomerulosclerosis is a very common cause of nephrotic syndrome that occurs in all ages. African Americans are affected more frequently than Cau-casians.

The condition may be idiopathic (primary), or it may be related to a wide variety of predisposing conditions including loss of renal tissue; preexisting glomerular diseases (such as IgA nephropathy); sickle cell anemia; heroin use; AIDS; or morbid obesity. Inherited and congenital forms occur.

Renal biopsy. Light microscopy shows focal segmental sclerosis and hyalinization of glomeruli; focal segmental glomerulosclerosis initially affects the glomeruli along the medullary border. Immunofluorescence shows IgM and C3 deposits in the scle-rotic segments. Electron microscopy shows effacement of foot processes in nonscle-rotic regions and increased mesangial matrix in sclerotic segments.

Clinical course. There is frequently a poor response to steroids, with the overall prognosis being poor (most progressing to chronic renal failure), though children do better than adults. There is a high rate of recurrence in renal transplants. A variant form, collapsing glomerulopathy, has a worse prognosis.