CRP-45

CRP-45

Clinical History

Fabry's disease, proteinuria, mild chronic renal insufficiency and hypertension. Ultrasound shows right kidney 9.0 cm and left kidney 11.0 cm. BUN 15, creatinine 1.2, urinary protein 2.8 g/day, creatinine clearance 51 ml/min.

Gross Description

Received in transport media are two cores measuring 16 and 6 mm in length and 2 mm in diameter. Representative fragments are submitted for immunofluorescence, electron microscopy and light microscopy.

Pathology

Case CRP-045 Silver

Microscopic Description, Immunofluorescence, and Electron Microscopy

Microscopic Description

Light Microscopy

Sections contain three fragments of renal cortex, and two of these also contain small portions of renal medulla. There are forty-two glomeruli in the three levels. Twelve are obsolete, although most of these occur in the deepest cortex at the corticomedullary junction. Seven glomeruli show segmental collapse and focal adhesions to Bowman's capsule. However, the most striking change is the generalized enlargement and vacuolization of the glomerular visceral epithelial cells. Similar changes are noted focally in the glomerular mesangium. PASH and trichrome stains show mild focal interstitial fibrosis and tubular atrophy, although there is moderately severe interstitial fibrosis ac the corticomedullary junction around the large vessels. Occasional interstitial foam cells and vacuolated tubular epithelial cells are identified. There is no interstitial inflammation. There is moderately severe arterial and arteriolar sclerosis.

Immunofluorescence

There are ten glomeruli in the sections. There is diffuse granular mesangial staining that is graded 2+ for IgM and IgA, although the IgA staining is definitely slightly less intense than the IgM staining. There is focal and segmental trace mesangial staining for kappa and lambda. There is l+ focal and segmental staining for C3 and Clq. There is no glomerular staining for IgG or albumin. Tubular epithelium contains numerous protein droplets that stain for IgA, C3, albumin and light chains. There is no staining of the tubular basement membranes. There is 4+ staining for C3 in the vessel walls.

Electron Microscopy

Four thick sections containing a total of four glomeruli are available. One shows segmental collapse. By light microscopy, numerous inclusions are easily visible in the visceral epithelial cells. Ultrastructural examination confirms the presence of numerous lamellated lipid inclusions ("myeloid bodies") in the visceral epithelium, as well as a few inclusions in mesangial, endothelial and parietal epithelial cells. Occasional inclusions are also noted in tubular epithelium and vascular myocytes. The capillary basement membranes are not significantly thickened, but there is diffuse fusion of the foot processes. Some capillary loops are occluded by long curved structures that have been called membranous convoluted structures. These structures have been described in many disease and even in normal glomeruli. They are thought to arise from focal lysis of cellular elements that are part of the membrane material, and they appear to have no clinical significance. No immune complex deposits are identified.

Diagnosis and Comments

Kidney, needle biopsy - Fabry's disease.

These light and electron microscopic features are typical of Fabry's disease. The segmental glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arterial and arteriolar sclerosis are typically seen in the latter stages of this disease. There is no evidence for a superimposed immune complex-mediated glomerulopathy. Overall, tubulointerstitial scarring is relatively mild.

Protein in the urine is indicative of glomerular dysfunction.

Aortic insufficiency refers to the inability of the aortic valve to close properly, thus allowing regurgitation of blood into the left ventricle during diastole -- i.e., volume overload. Disease of the aortic valve leaflets is a common cause of insufficiency.

Blood urea nitrogen (BUN) is used as a measure of the glomerular filtration rate and is increased in renal failure.