Thrombotic Microangiopathy (TMA) in the Setting of Pauci-Immune Crescentic Glomerulonephritis (GN)
KJ Henriksen, SM Meehan, A Chang. University of Chicago Medical Center, Chicago, IL
Background: The most common adult crescentic GN is associated with circulating antineutrophil cytoplasmic autoantibodies (ANCAs), which have been directly implicated in this severe renal injury. We have observed TMA in a subset of pauci-immune crescentic GN cases, and we performed a clinicopathologic study to understand the significance of TMA in the setting of pauci-immune crescentic GN.
Design: We reviewed the renal pathology archives over a 3 year period and identified 43 patients with pauci-immune crescentic GN, 10 of which had concurrent findings of TMA. We correlated the histologic findings with relevant clinical information. Only one patient had malignant hypertension, whereas the other nine patients had no known cause of TMA (e.g. thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, scleroderma, or anti-phospholipid antibody syndrome).
Results: Ten of 43 patients (23%) with biopsy-proven, pauci-immune GN had concurrent findings of TMA on histologic examination. All 10 patients presented with acute renal failure, with an average serum creatinine (Cr) of 5.7 mg/dL (range: 2.3-12.0 mg/dL), which did not differ significantly from the 33 patients without evidence of TMA, with an average serum Cr of 4.9 mg/dL (range: 1.2-12.1 mg/dL, p=0.295). Of the 10 patients with pauci-immune GN and concurrent TMA, one presented with malignant hypertension, while 2 others had a long-standing history of hypertension. Other possible etiologic causes of TMA were not identified with the available clinical information. Five patients presented with hematuria, and 2 with nephrotic-range proteinuria. Two biopsies demonstrated focal reduplication of the glomerular basement membranes. Fibrinoid necrosis of arteries and arterioles was present in 4 biopsies. Seven biopsies showed a predominance (>70%) of active lesions, specifically, cellular crescents with necrosis. Four biopsies demonstrated severe acute interstitial inflammation and five demonstrated tubulitis. Interstitial fibrosis and tubular atrophy were patchy and mild in all biopsies.
Conclusions: TMA is often associated with the acute phase of ANCA-associated crescentic GN. These patients are likely to present with markedly increased Cr values, and often with severe hematuria or proteinuria. Recent discoveries of autoantibodies against lysosomal-associated membrane protein-2, a previously recognized ANCA antigen that is abundantly expressed on endothelial cells, suggests that TMA may be an important component to the renal injury that is sustained in pauci-immune crescentic GN.
Category: Kidney (does not include tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 242, Wednesday Afternoon