PLASMA INHIBITORS OF CLONERULAR FIBRINOLYSIS (GF) IN HUMAN RENAL DISEASE

Abstract

To detect a circulating inhibitor of GF, serial dilutions of human plasma were incubated with 2 frozen sections from a single normal human kidney. The slides were washed and studied by the fibrin slide technique. The Lysis Inhibitory Titer (LIT) was defined as the highest dilution completely inhibiting GF. Of 146 controls with normal urinalyses and renal function, none had a LIT greater than 1:2. Defining an elevated LIT as 1:8 or greater, we found an elevated LIT in plasma from 42 of 119 patients with various forms of renal disease including 14 of 14 patients with the Hemolytic-uremic Syndrome (HUS) and 15 of 57 with qlomerulonephritis. In patients with renal disease, no difference was found in the frequency of anemia, leukopenia, or prolonged PT when comparing patients with normal against those with elevated LIT. Diminished renal function (64% vs. 36%), thrombocytopenia (42% vs. 5%), and prolonged PTT (30% vs. 0%) were more common in patients with elevated LIT. No correlation was detected between the LIT and plasma concentrations of the antiplasmins α₁ -antitrypsin, α₂ -macroglobulin, and C₁ -esterase inhibitor. Daily analysis of plasma from 3 patients with HUS showed a close correlation between the LIT and clinical course. In each case, removal of the inhibitor from the plasma by peritoneal dialysis was associated with recovery of renal function. Results suggest that the inhibitor may play an important role in the pathogenesis of glomerular fibrin deposition.

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