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 uremic syndrome and thrombotic microangiopathy (n = 5), antiphospholipid syndrome (n = 6), diabetic nephropathy (n = 5), minimal change disease with cyclosporine 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 juxtaglomerular apparatus (n = 5, 35.7%), arteriolar lesions showing mucinous intimal thickening and lumen mucoid occlusions (n = 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, 28.6%). Chronic lesions in large arteries showed modifications such as fibrous intimal thickening (n = 13, 92.8%). The pattern of endothelial staining for endothelin-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, cyclosporine 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.
Mouthon
Luc
L
Université Paris Descartes, faculté de Médecine Paris Descartes, pôle de Médecine Interne, hôpital Cochin, Centre de référence pour les vascularites nécrosantes et la sclérodermie systémique, Assistance Publique-Hôpitaux de Paris (AP-HP), 75014 Paris, France. luc.mouthon@cch.aphp.fr
Mehrenberger
Marion
M
Teixeira
Luis
L
Fakhouri
Fadi
F
Bérezné
Alice
A
Guillevin
Loïc
L
Noël
Laure-Hélène
LH
D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism; D000328:Adult; D000368:Aged; D016736:Antiphospholipid Syndrome / Q000473:pathology; D019332:Endothelin-1 / Q000096:biosynthesis*; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000378:metabolism / Q000473:pathology*; D014841:von Willebrand Factor / Q000378:metabolism
D019332:Endothelin-1; D014841:von Willebrand Factor