Tissue factor pathway inhibitor expression in human crescentic glomerulonephritis

Background. Tissue factor (TF) pathway inhibitor (TFPI), the major endogeno us inhibitor of extrinsic coagulation pathway activation, protects renal fu nction in experimental crescentic glomerulonephritis (GN). Its glomerular e xpression and relationship to TF expression and fibrin deposition in human crescentic GN have not been reported. Methods. Glomerular TFPI, TF, and fibrin-related antigen (FRA) expression w ere correlated in renal biopsies from 11 patients with crescentic GN. Biops ies from 11 patients with thin basement membrane disease and two normal kid neys were used as controls. Results. TFPI was undetectable in control glomeruli but was detectable in i nterstitial microvessels. In crescentic biopsies, TFPI was detected in cell ular crescents and was more prominent in fibrous/fibrocellular crescents, i ndicating a correlation with the chronicity of crescentic lesions. TFPI app eared to be associated with macrophages but not endothelial or epithelial c ells. TFPI was generally undetectable in regions of the glomerular tuft wit h minimal damage. In contrast, TF and FRA were strongly expressed in region s of minimal injury, as well as in more advanced proliferative and necrotiz ing lesions. Despite prominent TF expression, FRA was less prominent in fib rous/fibrocellular crescents in which TFPI expression was maximal. Conclusions. These data suggest that TFPI is strongly expressed in the late r stages of crescent formation and is inversely correlated with the presenc e of FRA in human crescentic GN. This late induction of TFPI may inhibit TF activity and favor reduced fibrin deposition in the chronic stages of cres cent formation.