Relationship of Intraglomerular Coagulation and Platelet Aggregation to Glomerular Sclerosis

Abstract

In order to investigate the relationship between intraglomerular coagulation and glomerular sclerosis, the distribution of fibrin-related antigen (FRA) in glomeruli without extracapillary lesions was examined by immunoperoxidase microscopy in 80 patients with IgA nephropathy (IgA-N). A total of 302 glomeruli were examined, including 20 with global sclerosis, 31 with segmental sclerosis (SS glomeruli), and 251 nonsclerosed glomeruli. In the nonsclerotic areas of SS glomeruli, the deposition of FRA was significantly greater than in the nonsclerosed glomeruli. In the nonsclerosed glomeruli FRA was mainly found in the mesangium, while in the nonsclerotic areas of SS glomeruli FRA was not only present in the mesangium but also in the endothelium of the glomerular capillary loops. FRA-positive microclots were also often observed attached to the endothelium of the capillaries of the nonsclerotic areas of SS glomeruli. Cross-linked FRA was also observed in the endothelium of the same capillaries using the monoclonal antibody DD3B6/22. Deposition of von Willebrand factor (vWF) was greater in the endothelium than in the mesangium in the same areas. Aggregated platelets adhering to the glomerular capillary walls in these areas were frequently detected using the monoclonal antibody P2. Such distribution of platelets and vWF showed that the endothelium of the nonsclerotic areas of SS glomeruli was more severely damaged than that of nonsclerosed glomeruli. These findings suggest that endothelial cell damage might activate the intraglomerular coagulation, which might be one of the factors in the development of global glomerular sclerosis.

Intraglomerular Deposition of Intact Cross-Linked Fibrin in IgA Nephropathy and Henoch-Schönlein Purpura Nephritis

“…The sections were thaw mounted onto slides coated either with albu min or 0.2% neoprene, fixed in acetone for 5 min at room tempera ture. and stained either directly [ 1 ] or indirectly. FRA was delected directly using a monospecific goat antibody against human fibrino gen (Cappcl Laboratories.…”

“…High quantities of fibrin-related antigen (FRA) arc often detected in damaged glomeruli using antibodies against fibrinogen. Cross-linked FRA (XL-FRA) is often observed in the endothelium in injured glo meruli using the monoclonal antibody DD3B6/22 against ¿/-dimer [1], Glomerular infiltration of monocytes/macrophages is an important pathological finding in human and experimental glomerulonephritis [2], It is also known that glomerular macrophages express procoagulant activity in experimental glomerulonephritis [3]. However, few stud ies in human glomerulonephritis have elucidated intraglomerular fibrin production due to macrophage inva sion.…”

Renal Denervation Prevents Intraglomerular Platelet Aggregation and Glomerular Injury Induced by Chronic Inhibition of Nitric Oxide Synthesis

“…On activation, platelets undergo a sequence of events leading to aggregation, release vasoactive granule constituents, and then promote further aggregation to gether with the formation of thromboxane A?, resulting in vasoconstriction. Furthermore, activated platelets inter act with factors in the coagulation system and concomi tant release of platelet-derived growth factor may in fluence long-term reparative processes after glomerular injuries and promote mesangial expansion [18][19][20], Plate lets possess constitutive NO synthase which acts as a neg ative feedback mechanism to inhibit platelet activation [4] hence it is possible that the inhibition of intrinsic NO synthesis may induce intravascular platelet activation [3]. In the present study, glomeruli contained coarsely aggre gated platelets in the capillary lumen, while endothelial cells or mesangial cells were intact in the mild glomerular lesion in L-NAME-treated rats.…”

PKC α regulates thrombin‐induced PDGF‐B chain gene expression in mesangial cells

“…Activation of the coagulation pathway with thrombin production and fibrin deposition are features of severe vascular and proliferative glomerular diseases [1,2]. Through its proteolytic activity, thrombin cleaves a tethered ligand and leads to activation of the receptor which is a member of the seven transmembrane spanning class of receptors linked to G-proteins [3].…”