CRP-30

CRP-30

Clinical History

The patient is a 42 year old male who is status post double lung transplant two years ago for alpha-1-antitrypsin deficiency. The patient has nephrotic range proteinuria. BUN 44, creatinine 2.3, creatinine clearance 65 ml/min, urinary protein 6.5 g/24 hr. BP 144/90.

Gross Description

Received in transport media is one core measuring l.5 cm in length and 2 mm in diameter. Two l mm pieces are taken for EM, a 4 mm piece is taken for immunofluorescence, and the remaining tissue is processed for light microscopy.

Pathology

Case CRP-030 Trichrome

Microscopic Description, Immunofluorescence, and Electron Microscopy

Microscopic Description

Light Microscopy

The specimen consists of a fragment of renal cortex that contains at least 12 glomeruli. Five of these are obsolete. The remaining glomeruli show a range of morphology. Some of them show essentially normal morphology, but most show varying degrees of mesangial sclerosis with a few exhibiting segmental sclerosis and complete collapse of the capillary tufts. A few of the glomeruli also demonstrate prominent congestion. There is no glomerular necrosis, and no thrombi are identified in any of the glomeruli. Mesangial cellularity is only mildly increased. There is diffuse moderate interstitial fibrosis with corresponding tubular atrophy. Many of the remaining tubules demonstrate dilation, epithelial simplification and focal epithelial cell necrosis. Occasional lymphocytes and plasma cells are scattered throughout the interstitium, but there is no tubulitis. The most striking change in the biopsy is in the arterioles and small arteries. The arterioles uniformly show marked hyalinosis with almost complete obliteration of the lumina. The small arteries show moderate intimal mucoid thickening. Several of the arterioles also contain fibrin thrombi. None of the vessels demonstrate vasculitis.

Immunofluorescence

There are eighteen glomeruli in the sections. Three of these are obsolete. There is trace mesangial staining for IgM diffusely, and there is 2+ focal and segmental mesangial staining for IgM, IgA, C3 and light chains. Blood vessels show 2+ irregular staining for C3.

Electron Microscopy

Two thick sections containing a total of eleven glomeruli are available. One of these is obsolete, but the rest show essentially normal morphology by light microscopy. Ultrastructural examination reveals mild thickening of the glomerular basement membranes, and there is only focal fusion of the visceral cell foot processes. Mesangial regions are slightly expanded by matrix but there is no significant mesangial cell proliferation. No electron dense deposits are identified in the glomeruli. The tubules show atrophy and focal epithelial cell necrosis.

Diagnosis and Comments

Kidney, needle biopsy - Marked hyaline arteriolosclerosis and focal arteriolar thrombosis, consistent with cyclosporine-associated arteriopathy.

These findings are most consistent with cyclosporine arteriopathy. The vascular lesions are quite characteristic. However, similar histology may also be seen in thrombotic microangiopathy, which should be ruled out clinically. The sever degree of vascular injury portends a very poor prognosis for this kidney.

Protein in the urine is indicative of glomerular dysfunction.

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

The normal fibrinogen level is 184 to 412 mg/dL.