Endothelin-1 expression in scleroderma renal crisis

The objective of the study was to investigate the role of endothelin 1 in the pathogenesis of scleroderma renal crisis in patients with systemic sclerosis We used immunohistochemical analysis with anti endothelin 1 and anti-von Willebrand factor antibodies in comparing kidney biopsies from patients with systemic sclerosis and scleroderma renal crisis (n = 14), from normal kidneys (n = 5), and from patients with typical hemolytic urermic syndrome and thrombotic microangiopathy (n = 5), antiphospholipid syndrome (n = 6), diabetic nephropathy (n = 5), minimal change disease with cyclosponne toxicity (n = 5), or nephroangiosclerosis (n = 5) Kidney biopsies from all systemic sclerosis patients presented specific lesions glomerular lesions with thickened capillary walls (n = 6, 42 8%), mesangiolysis (n = 3, 21 4%), fibrin thrombi (n = 3, 21 4%), hypertrophy of juxtaglomenilar apparatus (n = 5 35 7%), arteriolar lesions showing mucinous intimal thickening and lumen mucoid occlusions (11 = 13, 92 8%), proliferation of intimal cells (ie, onion-skin" lesions, n = 13, 92 8%), fibrinoid necrosis (n = 3, 21 4%), and fibrin thrombosis (n = 4, 286%) Chronic lesions in large arteries showed modifications such as fibrous intimal thickening (n = 13, 92 8%) The pattern of endothelial staining for endothelm 1 in both glomeruli and arteriolar lesions appears to be specific for scleroderma renal crisis Glomerular endothelin-1 staining without arteriolar staining was seen in hemolytic uremic syndrome and isolated arteriolar staining (without glomerular staining) was seen in a number of conditions including antiphospholipid nephropathy, cyclosponne toxicity, and diabetic nephropathy Endothelin-1 is overexpressed in glomeruli and arterioles of patients with scleroderma renal crisis, which suggests that endothelin-1 might be a therapeutic target in this condition (C) 2011 Elsevier Inc All rights reserved