Recent evidence demonstrates that coagulation plays a role in mediating glomerular damage in patients with
systemic lupus erythematosus and diffuse proliferative
glomerulonephritis. Because of its beneficial effect in experimental
glomerulonephritis, we treated patients with
systemic lupus erythematosus and diffuse proliferative
glomerulonephritis with
ancrod, a
drug known to lower
fibrinogen levels and thought to activate fibrinolysis. Our patients had unusually severe renal disease; renal function was deteriorating in many. Before
ancrod, vascular
plasminogen activator levels were low, and levels of an inhibitor of
plasminogen activation were elevated. Some patients had elevated
plasmin inhibitor levels. Results were considered in two groups. In 13 patients characterized as fibrinolysis responders, the low vascular
plasminogen activator and increased
plasminogen activation inhibitor levels normalized. After
ancrod, striking resolution of microvascular
thrombosis occurred, which was associated with some improvement in renal function and blood pressure control. In five patients characterized as fibrinolysis nonresponders and who also had an elevated
plasmin inhibitor (alpha 2-antiplasmin) level, normalization of fibrinolysis did not occur. There was little change in microvascular
thrombosis, renal function, or blood pressure control in the fibrinolysis nonresponders. These preliminary observations demonstrate a disorder of fibrinolysis in patients with
systemic lupus erythematosus with microvascular thrombi in the kidney.
Ancrod therapy reverses this disorder rapidly in patients with a normal level of
plasmin inhibitor and may lead to repair of glomerular damage.