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.
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
Luc
L
Mouthon
Marion
M
Mehrenberger
Luis
L
Teixeira
Fadi
F
Fakhouri
Alice
A
Bérezné
Loïc
L
Guillevin
Laure-Hélène
LH
Noël
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