CRP-18

CRP-018

Clinical History

The patient is a 28 year old black female. History of SLE and mixed connective tissue disease. Postpartum (45 days ago); now admitted with hypertension, nephrotic sediment and acute renal failure. BUN 74, creatinine 2.2, creatinine clearance 48 ml/min, urinary protein 1.26 g/day. C3 and C4 normal, CH50 decreased, ANA positive, Smith positive, RNP positive. Urinalysis shows 3+ protein, 3+ blood, greater than 25 RBCs, 11 to 25 WBCs, RBC casts.

Gross Description

Received in transport media is one core measuring 15 mm in length and 2 mm diameter. A 5-mm fragment is taken for immunofluorescence, two 1-mm fragments are taken for EM, and the remaining tissue is submitted for light microscopy.

Pathology

Case CRP-018 Trichrome

Microscopic Description, Immunofluorescence, and Electron Microscopy

Microscopic Description

Light Microscopy

The specimen consists of a fragment of renal cortex that contains ninety-seven glomeruli in the three levels. None of these are obsolete, and none show segmental sclerosis. However, seven demonstrate segmental necrosis and mesangiolysis, and several glomeruli contain intracapillary thrombi. Many of the glomeruli demonstrate ischemic atrophy. All of the glomeruli show mildly increased mesangial matrix and mild mesangial hypercellularity. The silver stain shows no spikes along the capillary loops or double contours. There is striking hypertrophy of the juxtaglomerular regions. The PASH and trichrome stains show diffuse moderate interstitial fibrosis and tubular atrophy. There is no interstitial inflammation. There are striking changes in the arterioles and small arteries. Most of the arterioles are extremely thick, and many demonstrate fibrinoid necrosis. There is no inflammation associated with this fibrinoid necrosis. Some of the thrombi in afferent arterioles extend into the hilar region of the glomerulus. Arteries of interlobular size and smaller arcuate arteries show severe mucoid intimal thickening with concentrically arranged myointimal cellular proliferation (“onionskin" lesion). This thickening has caused considerable reduction in the arterial lumina. Many of these vessels contain fibrin in the thickened intima as well as fragmented red blood cells.

Immunofluorescence

There are eight glomeruli in the sections. There is 1+ mesangial staining for IgG, IgM, C3 and light chains. There is no mesangial staining for IgA, Clq, or albumin. There is no staining of the glomerular capillary loops for any of these reagents. Blood vessels show amorphous staining for IgM, Clq and C3. There is focal staining for C3 in the tubular basement membranes. Tubular epithelium contains occasional albumin droplets. There is strong speckled staining for IgG, IgA and light chains in the tubular epithelial nuclei.

Electron Microscopy

Two thick sections containing a total of five glomeruli are available. Ultrastructural examination confirms the mild increase in mesangial matrix, and occasional small mesangial deposits are identified. There is mild diffuse thickening of the capillary basement membranes, but no subendothelial widening is noted. No deposits are noted along the capillary loops.

Diagnosis and Comments

Kidney, needle biopsy - Scleroderma (scleroderma renal crisis) and mesangial glomerulonephritis, consistent with mixed connective tissue disease

This combination of immune complex-mediated mesangial glomerulonephritis with scleroderma vascular lesions is consistent with mixed connective tissue disease. However, the vascular lesion is by more the more serious, with features that are typical of sclerodermal renal crisis. Although there is no global or segmental glomerulosclerosis in this biopsy, the severity of the vascular injury suggest that such glomerular scarring is inevitable. Furthermore, there is already moderate tubular atrophy and interstitial fibrosis.

Renal failure is the severe reduction of renal function and often leads to reduced urinary output.

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

A normal partial thromboplastin time is 28 to 37 seconds.