Tissue factor and its inhibitor in human non-crescentic glomerulonephritis--immunostaining vs plasma and urinary levels

Abstract

Tissue factor (TF)-the most potent trigger of coagulation and emerging antiapoptotic, proliferative and angiogenic factor, along with its principal inhibitor (tissue factor pathway inhibitor, TFPI) are known to be involved in crescentic glomerulonephritis (GN). We studied the relationship between plasma and urinary levels as well as renal biopsy immunostaining of TF and TFPI antigens with reference to some clinical parameters in human chronic non-crescentic GN. We examined plasma and urinary levels of TF and total TFPI (pre-biopsy, ELISA) and the intensity of TF, TFPI 1 and TFPI 2 staining (immunoperoxidase histochemistry) in kidney biopsy specimens from 30 chronic GN patients. Plasma and urinary TF (uTF) were higher in patients than in 18 healthy individuals. In normal kidneys, TF and TFPI 1/2 antigens were undetectable in glomeruli while a distinct staining of both TFPI variants was observed in tubules and interstitial microvessels. In diseased kidneys, TF was strongly expressed in glomeruli but was undetectable in tubules. In contrast, staining for TFPI 1/2 was observed in glomeruli and tubules. Neither plasma nor urinary levels of the markers correlated with the intensity of TF and TFPI 1/2 staining in biopsy specimens. uTF was significantly associated with creatinine clearance (R = 0.489, P = 0.006) and urinary TFPI (R = 0.554, P = 0.014), and tended to be lower in proliferative vs non-proliferative GN [83 (0-617) vs 281 (10-805) pg/ml; P = 0.06]. The intrarenal TF/TFPI system is profoundly disturbed in chronic GN. Plasma and urinary concentrations of TF and TFPI probably do not reflect genuine activity of the disease, likely due to a confounding effect of kidney insufficiency. uTF measurement seems to be helpful in initial identification of proliferative GN, yet further studies are required to validate its use as a marker of glomerular injury in chronic GN.