Clinical History:

A 41-year-old man is found to have proteinuria on urinalysis performed as part of a yearly checkup by his physician. The dipstick urinalysis showed no blood, glucose, or ketones. The microscopic urinalysis revealed only 1 RBC/hpf and no WBC/hpf. Physical examination findings include 1+ pitting edema of the lower extremities to the knees. His blood pressure is 130/80. The rectal examination reveals no masses, but the stool guaiac is positive. The lungs are clear to auscultation and percussion. Palpation of the abdomen reveals no masses, and bowel sounds are present. Additional laboratory testing revealed a 24 hour urine protein of 4.1 gm. His serum creatinine was 4.2 with BUN of 40. He was referred to a nephrologist, and a renal biopsy was performed.

Images 5.1 and 5.2:

What does the light microscopic appearance demonstrate (image 5.2 is a Jones silver stain) in all glomeruli?

There is thickening of the glomerular capillary loops, but the cellularity is not increased. The silver stain demonstrates "spikes" along the basement membrane of the capillaries.

Image 5.3:

What is the pattern seen on immunofluorescence with antibody to IgG?

There is a diffuse granular pattern of staining.

Image 5.4:

What are the features demonstrated by electron microscopy?

There is thickening between the capillary basement membrane and overlying epithelial cells having fused foot processes with deposition of electron dense material and interposition of lighter basement membrane material (which formed the "spikes" seen on the silver stain).

Questions:

1. What is the differential diagnosis?

This is nephrotic syndrome in an adult. The most common cause is membranous glomerulonephritis, but minimal change disease, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis can also occur. Nephrotic syndrome can also occur with systemic diseases such as diabetes mellitus, infections such as hepatitis B, malignancies, and amyloidosis. SLE would be uncommon in this setting, but could occur. About 85% of cases of membranous GN are idiopathic.

2. What additional laboratory testing would be useful?

An ANA was negative. The serum IgG was slightly decreased, and serum complement levels were normal. His serum glucose was 110 mg/dl. He is HbsAg negative.

3. What additional workup is necessary in this case?

The positive stool guaiac suggests gastrointestinal hemorrhage. A colonoscopy was performed, and a 5 cm irregular exophytic mass found in the cecum. The most common malignancies associated with adult membranous GN are melanomas, lung cancers, and colon cancers.

4. What is the pathogenesis of the disease seen here?

MGN is a chronic antigen-antibody mediated disease in which the immune complexes are deposited in the glomerular capillaries. The antigen may be within the glomerular capillary (in idiopathic cases) or extrinsic to the kidney (in secondary causes).