fibrin and Glomerulonephritis

Henoch-Schönlein purpura (HSP) is the most common vasculitis in children, in whom prognosis is mostly dependent upon the severity of renal involvement. Nephritis is observed in about 30% of children with HSP. Renal damage eventually leads to chronic kidney disease in up to 20% of children with HSP nephritis in tertiary care centres, but in less than 5% of unselected patients with HSP, by 20 years after diagnosis. HSP nephritis and IgA nephropathy are related diseases resulting from glomerular deposition of aberrantly glycosylated IgA1. Although both nephritides present with similar histological findings and IgA abnormalities, they display pathophysiological differences with important therapeutic implications. HSP nephritis is mainly characterized by acute episodes of glomerular inflammation with endocapillary and mesangial proliferation, fibrin deposits and epithelial crescents that can heal spontaneously or lead to chronic lesions. By contrast, IgA nephropathy normally presents with slowly progressive mesangial lesions resulting from continuous low-grade deposition of macromolecular IgA1. This Review highlights the variable evolution of similar clinical and histological presentations among paediatric patients with HSP nephritis, which constitutes a challenge for their management, and discusses the treatment of these patients in light of current guidelines based on clinical evidence from adults with IgA nephropathy.

Topics: Child; Fibrin; Glomerulonephritis; Glomerulonephritis, IGA; Humans; IgA Vasculitis; Immunoglobulin A

In the past decade, numerous experimental studies of genetically engineered mice have confirmed the involvement of the coagulation/fibrinolysis system during glomerular inflammation and repair, revealing many unexpected biologic effects far beyond fibrin formation and clearance. Resident glomerular cells and macrophages seem to act in concert to ensure the long-term consolidation of local injury and progression toward glomerulosclerosis. These recent advances will probably pave the way to a new therapeutic approach to renal diseases. However, the balance governing glomerular permeability is very delicate, and many issues will have to be dealt with before targeting this system.

Topics: alpha-2-Antiplasmin; Animals; Blood Coagulation; Endothelial Cells; Fibrin; Fibrinolysis; Glomerular Mesangium; Glomerulonephritis; Humans; Lipoproteins; Plasminogen Activator Inhibitor 1; Thrombin

Evaluation of a renal biopsy can be intimidating, because observational data from histologic stains, direct immunofluorescence (IF), and electron microscopy must be integrated with clinical and laboratory data to arrive at the correct diagnosis. Numerous diagnostic categories usually merit consideration. The typical strategy to diagnose renal disease is heavily weighted toward analysis of the histologic pattern of glomerular injury. This focus on histology is understandable; histologic evaluation was the first analytic probe available and has driven the formulation of classification schemes. Evaluation of IF before review of the light microscopy facilitates diagnostic evaluation, because the possibilities are immediately reduced. This simplifies the crucial final step-clinical and histologic correlation. In this review, I discuss the information content of IF and provide an algorithmic approach to the major renal diseases based on an IF-driven dissection of the differential diagnosis.

Topics: Acute-Phase Proteins; Complement C3; Diagnosis, Differential; Fibrin; Fluorescent Antibody Technique; Fluorescent Dyes; Glomerulonephritis; Humans; Immunoglobulin Light Chains; Immunoglobulins; Staining and Labeling

Extracapillary glomerulonephritis are associated with fibrin deposition in the urinary space of the glomerulus. Such deposits were correlated with the severity of the disease and with a poor renal outcome. Fibrin formation involves an activation of the coagulation cascade either through the intrinsic pathway, Hageman factor being activated by the altered glomerular basement membrane, either by the extrinsic pathway, infiltrating monocytes and glomerular cells exhibiting a procoagulant activity i.e. thromboplastin or tissue factor. Treatments with heparin or warfarin were shown to decrease the severity of experimental glomerular diseases. A similar beneficial effect was obtained with a monocyte-depleting serum and more recently with a treatment by a tissue type plasminogen activator. Glomerular cells also produce a fibrinolytic activity which could be too low or uneffective on extracapillary fibrin deposits if they contain high amounts of plasminogen activator inhibitors. Thrombin has procoagulant activity, antifibrinolytic activity and has cellular chemotactic and proliferative effects. It could play a major role in the pathogenesis of crescent formation.

Topics: Animals; Fibrin; Glomerulonephritis; Hemostasis; Humans; Kidney Glomerulus; Thrombin

Topics: Animals; Extracellular Matrix; Fibrin; Fibrinolysis; Glomerulonephritis; Humans; Kidney Glomerulus; Macrophages; Transforming Growth Factor beta

Topics: Animals; Disease Models, Animal; Fibrin; Glomerulonephritis; Hemorrhage; Humans; Kidney Glomerulus; Tissue Plasminogen Activator

Our current understanding of glomerulonephritis has been established on the basis of experimental investigations. As shown in this short review, our knowledge is quite extensive, but still not enough to account for, in detail, the pathogenesis of diverse inflammatory processes occurring in the renal glomerulus. In this context, further correlated morphologic and immunopathologic studies need to be carried out. Fortunately, recent progress has been remarkable in revealing many possible chemical substances responsible for the mediation of various inflammations which may certainly encourage our experimental studies. Similarly, numerous new findings accumulated by basic immunology may be ready for application to the research about immunologic diseases, including many categories of glomerulonephritis. A modern immunologic aspect may also direct attention towards the immunologic background modulating inflammatory processes. It is expected that these possible future studies, in concert, will contribute to a comprehensive understanding of human glomerular diseases.

Topics: Animals; Antigen-Antibody Complex; Basement Membrane; Disease Models, Animal; Fibrin; Glomerular Mesangium; Glomerulonephritis; Monocytes; Rabbits; Rats

This article reviews the mediation systems participating or potentially participating in inflammatory disease, especially in immunologic injury of the glomerulus. Mediator systems are separated into 3 mechanisms: the first involves complement and neutrophils; the second involves systems unrelated to neutrophils and complement components from C3 to C9; and the third involves blood monocytes. Major emphasis is given to an analysis of factors that potentially participate in the second mechanism. These include humoral factors such as the coagulation system and Hageman factor systems and cellular factor such as platelets or cells resident in the glomerulus. Studies on a role of vasoactive amines are presented. The importance of separating neutrophil-dependent and -independent mechanisms in these studies is emphasized. A review of current knowledge of the biochemical mechanisms involved in the Hageman factor system is presented because of the potential role of these components in the development of inflammation.

Topics: Animals; Basement Membrane; Complement System Proteins; Factor XII; Fibrin; Fibrinogen; Glomerulonephritis; Immune Complex Diseases; Inflammation; Intrinsic Factor; Kidney Glomerulus; Nephritis; Rabbits; Rats

Topics: Animals; Basement Membrane; Fibrin; Fibrinogen; Fibrinolysis; Glomerular Filtration Rate; Glomerulonephritis; Humans; Kidney Diseases; Kidney Glomerulus; Male; Mice; Platelet Adhesiveness

Topics: Basement Membrane; Blood Platelets; Capillaries; Cholesterol; Diabetic Nephropathies; Diabetic Retinopathy; Endothelium; Erythrocytes; Fibrin; Glomerulonephritis; Hemosiderin; Humans; Hyalin; Lipids; Microscopy, Electron; Retinal Vessels

Topics: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Chronic Disease; Female; Fibrin; Fibrinogen; Glomerulonephritis; Hemolytic-Uremic Syndrome; Humans; Immune Complex Diseases; Immunoglobulin A; Immunoglobulin G; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Middle Aged; Nephritis; Nephrosis; Nephrotic Syndrome; Purpura; Streptococcal Infections

Topics: Acute Kidney Injury; Animals; Blood Coagulation; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinolysis; Glomerulonephritis; Graft Rejection; Hemolytic-Uremic Syndrome; Heparin; Humans; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Mice; Phagocytosis; Pre-Eclampsia; Pregnancy; Rabbits; Transplantation, Homologous

Topics: Arthritis; Blood Coagulation Factors; Blood Platelets; Chronic Disease; Complement System Proteins; Connective Tissue; Disseminated Intravascular Coagulation; Endotoxins; Factor XII; Fibrin; Fibrinogen; Fibrinolysin; Glomerulonephritis; Humans; Inflammation; Kinins; Leukocytes; Nephritis; Shwartzman Phenomenon

Topics: Autoantibodies; Autoimmune Diseases; Basement Membrane; Blood Coagulation; Complement System Proteins; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immune Complex Diseases; Immunoglobulin E; Kidney Glomerulus; Nephrotic Syndrome

Topics: Anticoagulants; Antigens; Blood Coagulation; Chemical Fractionation; Chromatography, DEAE-Cellulose; Chromatography, Gel; Disseminated Intravascular Coagulation; Erythrocytes; Female; Fibrin; Fibrinogen; Fibrinolysin; Glomerulonephritis; Hemagglutination Inhibition Tests; Hemagglutination Tests; Humans; Immunodiffusion; Immunoelectrophoresis; Immunologic Techniques; Pregnancy; Protein Conformation; Staphylococcus; Tannins; Thrombin

Topics: Amyloid; Animals; Antibodies; Antibody Specificity; Bacteria; Basement Membrane; Blood Cells; Cell Membrane; Eukaryota; Ferritins; Fibrin; Fungi; Glomerulonephritis; Histological Techniques; Intestinal Mucosa; Microscopy, Electron; Rickettsia Infections; Sea Urchins; Virus Diseases; Viruses

Topics: Animals; Anti-Inflammatory Agents; Antibodies; Antigens; Antineoplastic Agents; Autoimmune Diseases; Complement System Proteins; Corticosterone; Fibrin; Glomerulonephritis; Humans; Mice; Mice, Inbred NZB; Mice, Inbred Strains; Nephritis; Plasmodium malariae; Rodent Diseases

The experimental and clinical observations analyzed in this review suggest that the deposition of fibrin within glomeruli is an important pathogenic mechanism in the series of events leading to progressive destruction of glomerular capillaries. Neither the causal factors nor the consequences of this type of reaction are peculiar to the glomerulus. Fibrin deposits can occur in any injured blood vessel and, if not rapidly dealt with by fibrinolysis, will lead to endothelial changes and the development of organizing thrombi. It seems that glomerular capillaries are especially vulnerable; there are several reasons for this. First, some immunologic reactions are triggered within the glomeruli and thus produce a local inflammatory response, leading to fibrin deposition. Secondly, the glomerular filtration function allows a progressive local accumulation of potentially damaging particles, such as circulating fibrinogen derivatives (formed during generalized intravascular clotting), or phlogistic immune complexes (as a result of systemic antigen-antibody interaction); these too cause local injury and fibrin deposition. Finally, the glomerular obliteration resulting from the organization of such fibrin deposits leads to irreversible damage and so has more serious implications for the patient than if the lesions occurred elsewhere, where the formation of functionally useful new capillaries is often possible. It seems reasonable to propose, therefore, that the use of anticoagulant may be natural therapy in cases with the risk of rapid, massive, and continuous fibrin accumulation in glomeruli, where glomerular sclerosis and irreversible renal failure are likely.

Topics: Anticoagulants; Antigen-Antibody Complex; Antigen-Antibody Reactions; Basement Membrane; Blood Coagulation; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Endocarditis, Bacterial; Fibrin; Glomerulonephritis; Humans; Hyalin; Kidney Diseases; Kidney Glomerulus; Lupus Erythematosus, Systemic; Phagocytosis; Purpura

Topics: Autoimmune Diseases; Biopsy; Blood Coagulation Disorders; Blood Protein Electrophoresis; Diagnosis, Differential; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Humans; Immunoelectrophoresis; Kidney; Kidney Diseases; Kidney Glomerulus; Pre-Eclampsia; Pregnancy

Topics: Child; Child, Preschool; Clinical Trials as Topic; Fibrin; Glomerulonephritis; Humans; Kidney Diseases

Treatment with indomethacin, aspirin, or prednisone has been shown to reduce urinary fibrin/fibrinogen degradation products (F.D.P.) in approximately two-thirds of patients with proliferative glomerulonephritis. This reduction which is dose-dependent for prednisone but not for indomethacin or aspirin in the range of doses used occurs within two to three days of beginning treatment and is thought to result from decreased intraglomerular fibrin deposition rather than alteration of glomerular permeability to F.D.P. In patients who responded in this manner treatment was associated with reductions in the degree of proteinuria and maintenance or improvement in renal function.

Topics: Adolescent; Adult; Aged; Aspirin; Child; Creatinine; Female; Fibrin; Fibrinogen; Glomerulonephritis; Humans; Indomethacin; Kidney Glomerulus; Male; Middle Aged; Plasminogen; Prednisone; Proteinuria; Time Factors; Urea

Glomerulonephritis is an acquired serious glomerular disease, which involves the interplay of many factors such as cytokines, chemokines, inflammatory cells, and heparan sulfate (HS). We previously showed that blocking of inflammatory heparan sulfate domains on cultured glomerular endothelium by specific anti-HS single chain antibodies reduced polymorphonuclear cell (PMN) adhesion and chemokine binding. We hypothesized that injection of anti-HS antibodies in PMN-driven experimental glomerulonephritis should reduce glomerular influx of PMNs and thereby lead to a better renal outcome. In contrast to our hypothesis, co-injection of anti-HS antibodies did not alter the final outcome of anti-glomerular basement membrane (anti-GBM)-induced glomerulonephritis. Glomerular PMN influx, normally peaking 2 hours after induction of glomerulonephritis with anti-GBM IgG was not reduced by co-injection of anti-HS antibodies. Four days after induction of glomerulonephritis, albuminuria, renal function, glomerular hyalinosis and fibrin deposition were similar in mice treated and not treated with anti-HS antibodies. Interestingly, we observed transient effects in mice co-injected with anti-HS antibodies compared to mice that did not receive anti-HS antibodies: (i) a decreased renal function 2 hours and 1 day after induction of glomerulonephritis; (ii) an increased albuminuria after 2 hours and 1 day; (iii) an increased glomerular fibrin deposition after 1 day; (iv) a reduced glomerular macrophage influx after 1 day; (v) a sustained glomerular presence of PMNs at day 1 and 4, accompanied by an increased renal expression of IL-6, CXCL1, ICAM-1, L-selectin, CD11b and NF-κB. The mechanism underlying these observations induced by anti-HS antibodies remains unclear, but may be explained by a temporarily altered glycocalyx and/or altered function of PMNs due to the binding of anti-HS antibodies. Nevertheless, the evaluated anti-HS antibodies do not show therapeutic potential in anti-GBM-induced glomerulonephritis. Future research should evaluate other strategies to target HS domains involved in inflammatory processes during glomerulonephritis.

Topics: Animals; CD11b Antigen; Chemokine CXCL1; Fibrin; Gene Expression Regulation; Glomerulonephritis; Heparitin Sulfate; Intercellular Adhesion Molecule-1; Interleukin-6; Kidney Glomerulus; L-Selectin; Mice; Single-Chain Antibodies

Topics: Adult; Antiviral Agents; Bone Marrow; Cytomegalovirus; Cytomegalovirus Infections; Fibrin; Glomerulonephritis; Granuloma; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Viral Load

Inflammation is regulated by endogenous mechanisms, including anti-inflammatory cytokines, adenosine, and the nicotinic acetylcholine receptor α7 subunit (α7nAChR). We investigated the role of α7nAChR in protection against the progression of tissue injury in a model of severe, macrophage-mediated, cytokine-dependent anti-glomerular basement membrane (GBM) glomerulonephritis (GN), in α7nAChR-deficient (α7(-/-)) mice . At d 7 after the injection of anti-GBM antibody, kidneys from α7(-/-) mice displayed severe glomeruli (P < 0.0001) and tubulointerstitial lesions (P < 0.001) compared to kidneys from WT mice. An important finding was the presence of severe glomerulosclerosis in α7(-/-) mice in this early phase of the disease. Kidneys of α7(-/-) mice showed greater accumulation of inflammatory cells and higher expression of chemokines and cytokines than did those of WT mice. In addition, in α7(-/-) fibrotic kidneys, the expression of fibrin, collagen, TGF-β, and tissue inhibitor of metalloproteinase (TIMP)-2 increased, and the expression of TIMP3 declined. The increase in counterregulatory responses to inflammation in α7(-/-) nephritic kidneys did not compensate for the lack of α7nAChR. These findings indicate that α7nAChR plays a key role in regulating the inflammatory response in anti-GBM GN and that disruption of the endogenous protective α7nAChR amplifies inflammation to accelerate kidney damage and fibrosis.

Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Collagen; Cytokines; Disease Models, Animal; Female; Fibrin; Fibrosis; Glomerular Basement Membrane; Glomerulonephritis; Inflammation; Kidney; Macrophages; Male; Mice; Mice, Inbred C57BL; Protein Subunits; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinase-3; Transforming Growth Factor beta

Inflammation and thrombosis coexist in several disorders. Although it is recognized that leukocytes may induce a procoagulant state at sites of inflammation, the critical molecular determinants of this process remain largely unknown.. To examine mechanisms of inflammation-induced thrombosis, we developed a murine model of thrombotic glomerulonephritis (TGN), a known cause of acute renal failure in patients. This model, induced by lipopolysaccharide and antibody to the glomerular basement membrane, led to rapid glomerular neutrophil recruitment, thrombotic glomerular lesions with endothelial cell injury, and renal dysfunction. In mice immunodepleted of neutrophils or lacking the leukocyte-specific integrin Mac-1, neutrophil recruitment, endothelial injury, glomerular thrombosis, and acute renal failure were markedly attenuated despite the robust generation of renal cytokines. Neutrophil elastase is a likely effector of Mac-1 because its activity was reduced in Mac-1-deficient mice and the phenotype in mice deficient in Mac-1 or neutrophil elastase was similar. Platelets accumulated in glomerular capillaries within 4 hours of TGN before evidence of thrombosis. Platelet immunodepletion before TGN markedly exacerbated hematuria (hemorrhage), inflammation, and injury, whereas thrombocytopenic Mac-1-deficient mice remained resistant to disease, indicating that initial glomerular platelet deposition protects the vessel wall from neutrophil-mediated sequelae. The subsequent thrombosis relied on the interaction of Mac-1 on recruited neutrophils with glycoprotein Ibalpha on platelets as antibody-mediated disruption of this interaction attenuated TGN without affecting renal neutrophil accumulation.. These observations establish Mac-1 on neutrophils as a critical molecular link between inflammation and thrombosis and suggest it as an attractive target for antithrombotic therapy.

Topics: Acute Kidney Injury; Animals; Antibodies; Blood Platelets; Cytokines; Disease Models, Animal; Female; Fibrin; Glomerulonephritis; Leukocyte Elastase; Macrophage-1 Antigen; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neutrophils; Platelet Glycoprotein GPIb-IX Complex; Thrombocytopenia; Thrombosis

The activity of plasmin plays a critical role in the development of chronic glomerulonephritis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a potent inhibitor of plasmin generation. We hypothesized that TAFI is involved in the pathogenesis of glomerulonephritis because it inhibits plasmin generation. To demonstrate this hypothesis, we compared the development of immune complex-mediated glomerulonephritis in wild-type and TAFI-deficient mice. After six weeks of treatment with horse spleen apoferritin and lipoplysaccharide to induce glomerulonephritis, mice deficient in TAFI had significantly better renal function as shown by lower concentrations of albumin in urine and blood urea nitrogen compared to wild-type mice. In addition, the activity of plasmin and matrix metalloproteinases was significantly increased, and mesangial matrix expansion and the deposition of collagen and fibrin in kidney tissues were significantly decreased in TAFI-knockout mice as compared to their wild-type counterparts. Depletion of fibrinogen by batroxobin (Defibrase) treatment led to equalization of the renal function and the amount of collagen deposition in the kidneys of TAFI-knockout and wild-type mice with immune complex-mediated glomerulonephritis. Together these observations suggest that TAFI-mediated inhibition of plasmin generation plays a role in the pathogenesis of glomerulonephritis, and that it may constitute a novel molecular target for the therapy of this disease.

Topics: Animals; Antigen-Antibody Complex; Batroxobin; Carboxypeptidase B2; Complement C3; Cytokines; Disease Models, Animal; Disease Progression; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Fibrosis; Glomerulonephritis; Kidney; Kidney Function Tests; Matrix Metalloproteinases; Mice; Mice, Knockout; Time Factors

The role of thrombospondin 2 (TSP2) was investigated in an anti-glomerular basement membrane (GBM) nephritis model that compared TSP2-null mice with wild-type (WT) controls. TSP2-null mice were analyzed for kidney function, renal cortical matrix expansion, influx of inflammatory cells, proliferation, and apoptosis, as well as for capillary rarefaction after induction of anti-GBM disease. Whereas the renal cortex of normal control WT mice did not show any detectable TSP2 staining above background, TSP2 protein expression was clearly upregulated in anti-GBM disease. TSP2 deficiency led to an accelerated and enhanced inflammatory response, as indicated by the influx of CD4(+) and CD8a(+) cells and monocytes/macrophages. Glomerular fibrin deposition and a matrix-remodeling response were also observed, as indicated by collagens I and IV staining and a proliferative response within the renal interstitium. These changes were accompanied by increased matrix metalloproteinase 2 activity and enhanced alpha-smooth muscle actin staining in the TSP2-null mice. Neither a compensatory increase in TSP1 nor increased phosphorylation of Smad 2/3, an indicator for TGF-beta activity, was observed. The proliferative response of the peritubular endothelium was accelerated and enhanced, leading to a reversal of capillary rarefaction in TSP2-null mice, whereas interstitial cell death was equivalent to that in WT mice. In conclusion, the lack of the matricellular protein TSP2 in mice accelerates and enhances several responses to renal injury and reveals an important role for TSP2 as a major endogenous antiangiogenic and matrix metalloproteinase 2-regulating factor in renal disease.

Topics: Angiogenesis Inhibitors; Animals; Apoptosis; Cell Adhesion Molecules; Cell Proliferation; Fibrin; Glomerular Basement Membrane; Glomerulonephritis; Inflammation; Kidney Cortex; Kidney Glomerulus; Matrix Metalloproteinase 2; Mice; Mice, Knockout; Neovascularization, Pathologic; Thrombospondins

Protease-activated receptor-2 (PAR-2) is a cellular receptor expressed prominently on epithelial, mesangial, and endothelial cells in the kidney and on macrophages. PAR-2 is activated by serine proteases such as trypsin, tryptase, and coagulation factors VIIa and Xa. It induces pleiotropic effects including vasodilatation, increasing plasminogen activator inhibitor (PAI-1) expression, mesangial cell proliferation, and cytokine production by macrophages. The role of PAR-2 in renal inflammation was studied in antiglomerular basement membrane antibody-induced crescentic glomerulonephritis (CGN) using PAR-2-deficient (PAR-2(-/-)) mice and wild-type littermate controls. PAR-2(-/-) mice had reduced crescent formation, proteinuria, and serum creatinine compared with wild-type mice 21 days after initiation of CGN. Glomerular accumulation of CD4(+) T cells and macrophages and the number of proliferating cells in glomeruli were similar in both groups. Glomerular fibrin deposition was significantly reduced in PAR-2(-/-) mice, and this was associated with reduced renal plasminogen activator inhibitor expression and increased renal matrix-metalloprotinase-9 activity. These results demonstrate a proinflammatory role for PAR-2 in CGN that is independent of effects on glomerular leukocyte recruitment and mesangial cell proliferation. PAR-2-mediated augmentation of renal plasminogen activator inhibitor expression and inhibition of matrix-metalloprotinase-9 activity may contribute to increased glomerular fibrin accumulation and glomerular injury in CGN.

Topics: Animals; Fibrin; Glomerulonephritis; Kidney Glomerulus; Matrix Metalloproteinases; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide; Receptor, PAR-2; Serpin E2; Serpins; Thromboplastin; Transforming Growth Factor beta1

Mast cells are detrimental in several inflammatory diseases; however, their physiological roles are also increasingly recognized. Recent data suggest that mast cells may also be involved in renal diseases. We therefore used congenitally mast cell-deficient W/W(v) mice and normal +/+ littermates to assess their role in anti-glomerular basement membrane-induced glomerulonephritis. Following administration of anti-glomerular basement membrane Abs, W/W(v) mice exhibited increased mortality as compared with +/+ mice owing to rapid deterioration of renal function. Reconstitution of the mast cell population in W/W(v) mice restored protection. This was independent of activating FcgammaR, as protection was also obtained using mast cells deficient in FcRgamma. Comparative histological analysis of kidneys showed that deterioration of renal function was caused by the presence of thick layers of subendothelial glomerular deposits in W/W(v) mice, while +/+ mice or mast cell-reconstituted W/W(v) mice showed significantly less. Deposits appeared during the early phase of disease and persisted thereafter, and were accompanied by enhanced macrophage recruitment. Immunohistochemical analysis revealed increased amounts of fibrin and type I collagen in W/W(v) mice, which were also unable to maintain high tissue plasminogen activator and urinary-type plasminogen activator activity in urine in the heterologous phase of disease. Our results indicate that mast cells by their ability to mediate remodeling and repair functions are protective in immune complex-mediated glomerulonephritis.

Topics: Animals; Antibodies; Cell Proliferation; Collagen; Cricetinae; Disease Susceptibility; Endothelial Cells; Fibrin; Glomerular Basement Membrane; Glomerulonephritis; Macrophages; Mast Cells; Mice; Receptors, IgG; Survival Rate

Recent data indicated that aging accelerated glomerular fibrin deposition induced by lipopolysaccharide (LPS) in mice. Our hypothesis was that aging may exacerbate glomerular inflammatory responses induced by glomerular fibrin deposition. Both young and aged rats with glomerular fibrin deposition induced by LPS were treated with tranexamic acid (TA) and TA plus urokinase (UK). Infiltrating inflammatory cells and expressions of monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular endothelial-cadherin were markedly upregulated in the LPS+TA group compared with the LPS group. Reduction of fibrin deposition in the LPS+TA+UK group was associated with downregulation of the above indices (p < .05), whereas the alteration of vascular endothelial-cadherin protein expression was negatively correlated with the fibrin deposition. There were also significant differences in increased expressions of monocyte chemoattractant protein 1 and intercellular adhesion molecule 1 between young and aged rats. These in vivo data demonstrated that fibrin deposition contributed to glomerular inflammatory responses, which could be exacerbated by aging.

Topics: Aging; Animals; Antifibrinolytic Agents; Antigens, CD; Blotting, Northern; Cadherins; Chemokine CCL2; Female; Fibrin; Glomerulonephritis; Immunohistochemistry; Intercellular Adhesion Molecule-1; Kidney Glomerulus; Lipopolysaccharides; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tranexamic Acid; Urokinase-Type Plasminogen Activator

Goodpasture's, or anti-glomerular basement membrane (GBM), disease presents with rapidly progressive glomerulonephritis and lung haemorrhage, and is caused by autoimmunity to the NC1 domain of the alpha3 chain of type IV collagen (alpha3(IV)NC1). This study examines the development of crescentic nephritis and alveolar haemorrhage in a model of Goodpasture's disease, experimental autoimmune glomerulonephritis (EAG), induced in WKY rats by immunization with rat GBM in adjuvant. An increase in circulating anti-GBM antibodies and albuminuria was observed by week 2, which increased further by weeks 3 and 4, while a decrease in creatinine clearance was observed by week 2, which decreased further by weeks 3 and 4. The kidneys of animals with EAG showed linear deposits of IgG on the GBM and a transient glomerular infiltration by CD4+ T cells at week 2. By week 3 there were large deposits of fibrin in Bowman's space, and glomerular infiltration by CD8+ T cells and macrophages, accompanied by focal necrotizing glomerulonephritis with crescent formation. Ultrastructural studies showed glomerular endothelial cell swelling and epithelial cell foot process effacement at week 2. As the lesion progressed, capillary loops became occluded and the mesangium became expanded by mononuclear cells. By week 3 there was detachment of the endothelium from the GBM, and accumulation of fibrin beneath the disrupted endothelial cells and in Bowman's space. Occasional breaks were observed in the continuity of the basement membrane, and cytoplasmic projections from infiltrating mononuclear cells could be seen crossing the capillary wall between the lumen and the crescent. The lungs of animals with EAG showed patchy binding of IgG to the alveolar basement membrane (ABM) at week 2, and infiltration of the interstitium by CD8+ T cells and macrophages by weeks 3 and 4, accompanied by both interstitial and alveolar haemorrhage. Ultrastructural studies showed focal mononuclear cell infiltrates in alveolar walls at week 2. Occasional breaks were observed in the basement membrane and adjacent endothelium by weeks 3 and 4, together with accumulation of surfactant and erythrocytes within the alveolar spaces. This study defines for the first time the relationship between the immunological and pathological events during the evolution of EAG, and provides the basis for further work on the pathogenesis of Goodpasture's disease.

Topics: Animals; Anti-Glomerular Basement Membrane Disease; Antibodies; Autoantibodies; Autoimmune Diseases; Autoimmunity; Basement Membrane; Creatinine; Disease Models, Animal; Fibrin; Glomerulonephritis; Hemorrhage; Kidney Glomerulus; Lung Diseases; Male; Microscopy, Electron; Nephritis; Pulmonary Alveoli; Rats; Rats, Inbred WKY

Crescentic glomerulonephritis is characterized by glomerular fibrin deposition, and experimental crescentic glomerulonephritis has been shown to be fibrin-dependent. Net fibrin deposition is a balance between activation of the coagulation system causing glomerular fibrin deposition and fibrin removal by the plasminogen-plasmin (fibrinolytic) system. Plasminogen activator inhibitor-1 (PAI-1) inhibits fibrinolysis by inhibiting plasminogen activators and has effects on leukocyte recruitment and matrix deposition. To test the hypothesis that the presence of PAI-1 and its levels were a determinant of injury in crescentic glomerulonephritis, accelerated anti-glomerular basement membrane glomerulonephritis was induced in mice genetically deficient in PAI-1 (PAI-1 -/-), PAI-1 heterozygotes (PAI-1 +/-), and mice engineered to overexpress PAI-1 (PAI-1 tg). Compared with strain-matched genetically normal animals, PAI-1 -/- mice with glomerulonephritis developed fewer glomerular crescents, less glomerular fibrin deposition, fewer infiltrating leukocytes, and less renal collagen accumulation at day 14 of disease. The reduction in disease persisted at day 28, when injury had become more established. In contrast, mice overexpressing the PAI-1 gene (PAI-1 tg), that have basal plasma and renal PAI-1 levels several times, normal developed increased glomerular crescent formation, more glomerular fibrin deposition, increased numbers of infiltrating leukocytes, and more renal collagen at both time points. These studies demonstrate that PAI-1 is a determinant of glomerular fibrin deposition and renal injury in crescentic glomerulonephritis.

Topics: Animals; Animals, Genetically Modified; Collagen; Fibrin; Glomerulonephritis; Kidney; Leukocyte Count; Leukocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; Plasminogen Activator Inhibitor 1; Severity of Illness Index; Time Factors

Macrophages are prominent participants in crescentic glomerulonephritis (GN) and have been suggested to be the major source of TNF in this cell-mediated form of glomerular inflammation. Intrinsic renal cells also have the capacity to produce TNF. For dissecting the contribution of local versus bone marrow (BM)-derived TNF in inflammatory renal injury, TNF chimeric mice were created by transplanting normal wild-type (WT) BM into irradiated TNF-deficient recipients (WT-->TNF-/- chimeras) and vice versa (TNF-/- -->WT chimeras). A model of crescentic GN induced by an intravenous injection of sheep anti-murine glomerular basement membrane antibody was studied in WT mice, mice with complete TNF deficiency (TNF-/-), and chimeric mice. Crescentic GN was attenuated in TNF-/- mice with fewer crescents (crescents, 13.7 +/- 1.7% of glomeruli) and reduced functional indices of renal injury (serum creatinine, 15.2 +/- 0.8 micromol/L). Similar protection (crescents, 14.3 +/- 1.9% of glomeruli; serum creatinine, 18.9 +/- 1.1 micromol/L) was observed in chimeric mice with intact BM but absent renal-derived TNF (WT-->TNF-/- chimeras), suggesting a minor contribution of infiltrating leukocytes to TNF-mediated renal injury. Chimeric mice with TNF-deficient leukocytes but intact intrinsic renal cell-derived TNF (crescents, 20.5 +/- 2.0% of glomeruli; serum creatinine, 21.6 +/- 1.4 micromol/L) developed similar crescentic GN to WT mice (crescents, 22.3 +/- 1.4% of glomeruli; serum creatinine, 24.8 +/- 1.9 micromol/L). Cutaneous delayed-type hypersensitivity after subdermal challenge with the nephritogenic antigen was attenuated in the absence of BM cell-derived TNF but unaffected in WT-->TNF-/- chimeric mice. These studies suggest that intrinsic renal cells are the major cellular source of TNF contributing to inflammatory injury in crescentic GN.

Topics: Actins; Animals; Basement Membrane; Bone Marrow Transplantation; CD4-Positive T-Lymphocytes; Creatinine; E-Selectin; Fibrin; Glomerulonephritis; Histocompatibility Antigens Class II; Hypersensitivity, Delayed; Intercellular Adhesion Molecule-1; Kidney; Macrophages; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Microscopy, Fluorescence; Proteinuria; Sheep; Tumor Necrosis Factor-alpha

Fibrin deposition is an important mechanism of glomerular injury in crescentic glomerulonephritis (GN), a severe form of immune renal injury. Both coagulation and fibrinolysis (via the plasminogen-plasmin system) are important in net glomerular fibrin accumulation in GN. alpha2-Antiplasmin (alpha2-AP) is the major circulating inhibitor of plasmin and is expressed in the renal tubulointerstitium.. To determine whether endogenous alpha2-AP contributes to glomerular fibrin accumulation in GN.. Crescentic autologous phase antiglomerular basement membrane GN was induced in mice with intact and deficient endogenous alpha2-AP (alpha2-AP+/+ and alpha2-AP-/- mice).. In mice with crescentic GN, alpha2-AP was detected in the tubulointerstitium and in segmental deposits within some glomeruli. alpha2-AP+/+ mice developed crescentic GN (38 +/- 9% glomeruli affected) with glomerular fibrin deposition and renal impairment (serum creatinine 30 +/- 1 micro mol L-1, normal without GN 11 +/- 1 micro mol L-1). Genetic deficiency of alpha2-AP did not result in attenuated glomerular fibrin deposition, crescent formation (39 +/- 8% glomeruli affected), glomerular leukocyte infiltration or renal impairment (serum creatinine 33 +/- 7 micro mol L-1). alpha2-AP was unmeasurable in kidneys from alpha2-AP-/- mice, which did not develop compensatory changes in plasminogen, tissue type plasminogen activator (tPA), urokinase type PA (uPA) or plasminogen activator inhibitor-1 proteins, or changes in tPA or uPA activity. alpha2-AP-/- mice did have enhanced total renal fibrinolytic capacity as assessed by in situ fibrin overlay (alpha2-AP+/+ 0.19 +/- 0.01, alpha2-AP-/- 0.36 +/- 0.03 lyzed area/total area).. alpha2-AP is not important to net glomerular fibrin deposition, crescent formation or renal impairment in crescentic GN.

Topics: alpha-2-Antiplasmin; Animals; Chemotaxis, Leukocyte; Fibrin; Fibrinolysis; Glomerulonephritis; Kidney Glomerulus; Mice; Mice, Knockout; Renal Insufficiency

Growth-arrest specific gene 6 (Gas6) is a vitamin K-dependent growth factor for mesangial and epithelial cells. To investigate whether Gas6 is essential for progressive glomerular injury, we constructed Gas6(-/-) mice and examined the role of Gas6 in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis. We found less mortality and proteinuria in Gas6(-/-) mice than in wild-type mice following injection of nephrotoxic serum. Glomerular cell proliferation, glomerular sclerosis, crescent formation, and deposition of fibrin/fibrinogen in glomeruli were also reduced in Gas6(-/-) mice. Furthermore, administering Gas6(-/-) mice recombinant wild-type Gas6, but not Gas6 lacking a previously characterized N-terminal gamma-carboxyl group, induced massive proteinuria, glomerular cell proliferation, and glomerulosclerosis, comparable to responses seen in wild-type mice. These data indicate that Gas6 induces glomerular cell proliferation in NTN and suggest that this factor contributes to glomerular injury and the progression of chronic nephritis.

Topics: Animals; Cell Division; DNA-Binding Proteins; Fibrin; Fibrinogen; Glomerulonephritis; Immunoglobulin G; Intercellular Signaling Peptides and Proteins; Kidney Glomerulus; Mice; Mice, Inbred C57BL; Mice, Knockout; Proteins; Recombinant Proteins; Sheep; STAT3 Transcription Factor; Trans-Activators

Coagulation and inflammation are both important processes that contribute to glomerular injury. The present study was performed to evaluate the effects of recombinant human soluble thrombomodulin (RHS-TM) in a lethal model of thrombotic glomerulonephritis and to investigate the possible mechanisms.. Thrombotic glomerulonephritis was induced in rats by administration of lipopolysaccharide and rabbit anti-rat glomerular basement membrane antibody. One hour later, RHS-TM or heparin was administered, and the histological findings, renal functions, and coagulation parameters were evaluated. To evaluate the contribution of carboxypeptidase R (CPR) to the results obtained in rats treated with RHS-TM, plasma CPR levels were measured. Then, carboxypeptidase inhibitor (CPI), which prevents the function of CPR, was administered.. Massive glomerular thrombosis and lung hemorrhage developed within five hours of disease induction, and all rats died within 24 hours. RHS-TM (3 mg/kg) prevented the progression of the disease and all rats survived. Heparin (250 U/kg/h) showed similar anti-thrombotic effect, but induced massive hemorrhage in the lungs or stomach. RHS-TM attenuated leukocyte/neutrophil infiltration in the glomerulus but heparin did not, suggesting that RHS-TM has anti-inflammatory properties. CPR levels in plasma were about threefold higher in rats treated with RHS-TM compared to those in rats treated with heparin. Furthermore, the inhibitory effect of RHS-TM on leukocyte/neutrophil infiltration was significantly diminished by injection of CPI.. RHS-TM effectively attenuates the injuries of thrombotic glomerulonephritis in rats. The results indicate that RHS-TM, in addition to its anti-thrombotic action, may exert its anti-inflammatory properties by converting proCPR to CPR, which then inactivates anaphylatoxins. RHS-TM is a potential novel therapeutic tool for thrombotic glomerular injury and related disorders.

Topics: Anaphylatoxins; Animals; Blood Coagulation; Blood Urea Nitrogen; Carboxypeptidase B2; Complement C5a; Creatinine; Disease Models, Animal; Female; Fibrin; Glomerulonephritis; Humans; Kidney Glomerulus; Leukocyte Count; Lysine Carboxypeptidase; Partial Thromboplastin Time; Platelet Count; Prothrombin Time; Rabbits; Rats; Rats, Wistar; Solubility; Thrombin; Thrombomodulin; Thrombosis

The autoantigen in Goodpasture's disease is known to be the non-collagenous domain of the alpha3 chain of type IV collagen, alpha 3(IV)NC1. There is mounting evidence that alpha 3(IV)NC1 is also a target of autoimmunity in experimental autoimmune glomerulonephritis (EAG). Sado et al. [Kidney Int 1998; 53, 664-671] have reported that recombinant human alpha 3(IV)NC1 and alpha4(IV)NC1 are nephritogenic in WKY rats. We have proposed that immunization with homologous antigen is more appropriate for detailed investigation of autoimmunity in EAG.. To this end, we have cloned and sequenced rat alpha 3(IV)NC1 and expressed it in COS-7 cells. Recombinant rat alpha 3(IV)NC1, secreted into the COS-7 cell supernatant, was purified on an anti-M2 FLAG affinity column and characterized by western blotting. Recombinant antigen was then used to immunize WKY rats, in order to induce EAG.. The recombinant material was antigenic as judged by binding to sera from patients with Goodpasture's disease and a mAb to alpha 3(IV)NC1. Immunization of WKY rats (n=5), with recombinant rat alpha 3(IV)NC1 in FCA at a dose of 1 mg/kg resulted in circulating anti-GBM antibodies directed towards alpha 3(IV)NC1, linear deposits of IgG on the GBM, albuminuria, deposits of fibrin in the glomeruli, severe focal necrotizing glomerulonephritis with crescent formation, and glomerular influx of CD8+ T cells and macrophages. Western blot analysis demonstrated that sera from these rats bound strongly to recombinant rat alpha 3(IV)NC1, as well as to collagenase-solubilized human and rat GBM. The pattern of binding was indistinguishable from that of sera from patients with Goodpasture's disease.. This purified recombinant rat alpha 3(IV)NC1, which is both antigenic and nephritogenic, will be of value in analysing autoimmune responses in experimental anti-GBM disease.

Topics: Albuminuria; Amino Acid Sequence; Animals; Antibodies; Autoantigens; Autoimmune Diseases; Base Sequence; Collagen; Collagen Type IV; Creatinine; Fibrin; Glomerulonephritis; Immunoglobulin G; Kidney; Male; Molecular Sequence Data; Rats; Rats, Inbred WKY; Recombinant Proteins

We report a case of crescentic glomerulonephritis that presented with extensive crescent formation and fibrinoid necrosis in the glomeruli. Immunofluorescence staining was strongly positive for linear and pseudolinear staining of the capillary walls for immunoglobulin G (IgG) in the absence of significant mesangial staining. Histologic examination and immunofluorescence staining suggested a diagnosis of anti-glomerular basement membrane disease. However, electron microscopy showed the presence of numerous fibrillary deposits in the subepithelial areas of the glomerular capillary walls, supporting the diagnosis of fibrillary glomerulonephritis. Test results for circulating anti-glomerular basement membrane antibodies were negative. We report this interesting case to illustrate the point that fibrillary glomerulonephritis should be considered in the differential diagnosis of crescentic glomerulonephritis with linear and pseudolinear IgG deposits within the capillary walls. In such cases, electron microscopy is critical in differentiating the cause of crescentic glomerulonephritis.

Topics: Acute Disease; Anti-Glomerular Basement Membrane Disease; Capillaries; Diagnosis, Differential; Fibrin; Glomerulonephritis; Humans; Immunoglobulin G; Kidney Glomerulus; Male; Microscopy, Fluorescence; Middle Aged

Interleukin (IL)-10 plays a pivotal role in regulating the Th1/Th2 predominance of immune responses. Exogenously administered IL-10 suppresses nephritogenic Th1 responses, inhibits macrophage function, and attenuates crescentic glomerulonephritis (GN). To determine the role of endogenous IL-10, the development of the nephritogenic immune response and crescentic GN was compared in IL-10-deficient (IL-10-/-) and normal (IL-10+/+) C57BL/6 mice.. GN was initiated in sensitized mice by the intravenous administration of sheep antimouse glomerular basement membrane globulin. Renal injury was evaluated 21 days later.. Following the administration of anti-glomerular basement membrane globulin, normal (IL-10+/+) C57BL/6 mice developed proliferative GN with occasional crescents, glomerular CD4+ T-cell and macrophage accumulation, and fibrin deposition. Using an identical induction protocol, IL-10-/-mice developed more severe GN. Crescent formation (IL-10-/-, 23 +/- 2% of glomeruli; IL-10+/+, 5 +/- 2%), glomerular CD4+ T cells [IL-10-/-, 1. 0 +/- 0.2 cells per glomerular cross-section (c/gcs); IL-10 +/+, 0.3 +/- 0.05 c/gcs], glomerular macrophages (IL-10-/-, 4.8 +/- 0.3 c/gcs; IL-10 +/+, 1.7 +/- 0.2 c/gcs), fibrin deposition [fibrin score (range 0 to 3+); IL-10-/-, 1.10 +/- 0.04; IL-10+/+, 0.6 +/- 0. 07], and serum creatinine (IL-10-/-, 30 +/- 2 micromol/L; IL-10 +/+, 23 +/- 1 micromol/L) were all significantly increased in IL-10-/- mice (P < 0.05). Circulating antibody (IL-10-/-, 1.05 +/- 0.16 OD units; IL-10+/+, 0.63 +/- 0.08 OD units) and cutaneous delayed-type hypersensitivity (skin swelling; IL-10-/-, 0.21 +/- 0.03 mm; IL-10+/+, 0.12 +/- 0.02 mm) to the nephritogenic antigen (sheep globulin) were also increased (both P < 0.05). Interferon-gamma production by cultured splenocytes was increased (IL-10-/- 7.9 +/- 2. 5 ng/4 x 106 cells, IL-10+/+ 0.28 +/- 0.09 ng/4 x 106 cells, P < 0. 05), but IL-4 production was unchanged.. Endogenous IL-10 counter-regulates nephritogenic Th1 responses and attenuates crescentic GN.

Topics: Animals; Antibodies; Autoantibodies; Complement C3; Cytokines; Female; Fibrin; Gene Expression; Glomerulonephritis; Hypersensitivity, Delayed; Immunoglobulins; Interferon-gamma; Interleukin-10; Kidney Glomerulus; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein Binding; Sheep; Species Specificity; Spleen; Th1 Cells

Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by a single injection of rat glomerular basement membrane (GBM) in adjuvant. EAG is characterized by circulating and deposited anti-GBM antibodies, accompanied by focal necrotizing glomerulonephritis with crescent formation. The role of T cells in the pathogenesis of EAG remains unclear. T-cell costimulation is provided by ligation of CD28 with either B7.1 (CD80) or B7.2 (CD86) on antigen-presenting cells, and can be inhibited by a soluble form of CTLA4 (CTLA4-Ig) that binds to both B7.1 and B7.2. We examined the effect of CD28-B7 blockade on the development of EAG using native CTLA4-Ig or mutant CTLA4-Ig (Y100F-Ig), which selectively blocks B7.1. Native CTLA4-Ig treatment ameliorated EAG by several measures, including the levels of circulating anti-GBM antibodies, albuminuria, the deposition of IgG and fibrin in the glomeruli, the severity of glomerular abnormalities, and the numbers of infiltrating T cells and macrophages. Y100F-Ig resulted in a similar reduction in the severity of nephritis, but produced no overall reduction in circulating anti-GBM antibodies, although there was a reduction in IgG2a antibodies. We concluded that CD28-B7 blockade reduced autoantibody production and cellular infiltration of glomeruli, and prevented target organ injury. Our results suggest a key role for B7. 1 in costimulation of Th1-like autoimmune responses in the rat, and show that glomerular injury in EAG is largely dependent on cell-mediated mechanisms.

Topics: Abatacept; Animals; Anti-Glomerular Basement Membrane Disease; Antigens, CD; Antigens, Differentiation; Autoantibodies; Autoimmune Diseases; B7-1 Antigen; Basement Membrane; CD28 Antigens; CTLA-4 Antigen; Disease Models, Animal; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Immunoconjugates; Immunoglobulin G; Kidney; Mutation; Rats; Rats, Inbred Strains; T-Lymphocytes

Tissue factor (TF) pathway inhibitor (TFPI), the major endogenous inhibitor of extrinsic coagulation pathway activation, protects renal function in experimental crescentic glomerulonephritis (GN). Its glomerular expression and relationship to TF expression and fibrin deposition in human crescentic GN have not been reported.. Glomerular TFPI, TF, and fibrin-related antigen (FRA) expression were correlated in renal biopsies from 11 patients with crescentic GN. Biopsies from 11 patients with thin basement membrane disease and two normal kidneys were used as controls.. TFPI was undetectable in control glomeruli but was detectable in interstitial microvessels. In crescentic biopsies, TFPI was detected in cellular crescents and was more prominent in fibrous/fibrocellular crescents, indicating a correlation with the chronicity of crescentic lesions. TFPI appeared to be associated with macrophages but not endothelial or epithelial cells. TFPI was generally undetectable in regions of the glomerular tuft with minimal damage. In contrast, TF and FRA were strongly expressed in regions of minimal injury, as well as in more advanced proliferative and necrotizing lesions. Despite prominent TF expression, FRA was less prominent in fibrous/fibrocellular crescents in which TFPI expression was maximal.. These data suggest that TFPI is strongly expressed in the later stages of crescent formation and is inversely correlated with the presence 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 crescent formation.

Topics: Adult; Antigens; Arterioles; Basement Membrane; Biopsy; Disease Progression; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Glomerulonephritis; Humans; Kidney Glomerulus; Lipoproteins; Male; Middle Aged; Thromboplastin

The pattern of glomerulonephritis (GN) developing in response to a planted antigen (sheep anti-mouse GBM globulin) was compared in two strains of mice which demonstrated either a predominant Th1 (C57BL/6) or Th2 (BALB/c) response to this antigen. GN was induced with a subnephritogenic i.v. dose of sheep anti-mouse GBM globulin in mice presensitized to sheep globulin. Sensitized C57BL/6 mice showed pronounced cutaneous delayed-type hypersensitivity (DTH) following the challenge with sheep globulin, low titers of circulating anti-sheep globulin antibody and high interferon gamma (IFN-gamma) and low interleukin 4 (IL-4) production by splenic T cells, consistent with a predominant Th1 pattern of immune response. Sensitized BALB/c mice did not develop DTH following cutaneous challenge with sheep globulin, had higher circulating anti-sheep globulin antibody titers, and showed high IL-4 and low IFN gamma production by splenic T cells compared with C57BL/6 mice, consistent with a predominant Th2 response. In C57BL/6 mice, GN developing in response to sheep globulin exhibited a severe crescentic pattern with prominent glomerular T cell and macrophage influx and fibrin deposition. In vivo depletion with a monoclonal anti-CD4 antibody demonstrated that this injury was T helper cell dependent. Treatment with monoclonal anti-mouse IFN gamma antibody significantly reduced glomerular injury and crescent formation and attenuated the cutaneous DTH response. GN induced by the same protocol in BALB/c mice exhibited pronounced glomerular IgG and complement deposition. Crescent formation, fibrin deposition, and glomerular T cell and macrophage infiltration were significantly less than observed in C57BL/6 mice, and injury was not T cell dependent in the effector phase. These data suggest that the pattern of glomerular injury induced by a planted antigen can be determined by the balance of T helper cell subset activation. A Th1 response induces a severe crescentic pattern of GN, which like cutaneous DTH, is T helper cell and IFN gamma dependent.

Topics: Animals; Antigens; Autoantibodies; CD4 Antigens; Complement System Proteins; Creatinine; Fibrin; Globulins; Glomerulonephritis; Hypersensitivity, Delayed; Immunoglobulin G; Immunoglobulins, Intravenous; Interferon-gamma; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Proteinuria; Sheep; T-Lymphocytes, Helper-Inducer

Increased glomerular tissue factor (TF) expression is associated with glomerular fibrin deposition and renal failure in human and experimental crescentic glomerulonephritis (GN). However, the in vivo functional contribution of TF to the development of glomerular fibrin deposition, crescent formation, and renal failure in GN has not been established. The contribution of TF to fibrin deposition and renal injury was studied in a rabbit model of crescentic GN in which glomerular macrophage infiltration, augmented TF expression, and fibrin deposition are prominent. Administration of anti-TF antibody inhibited glomerular TF activity in nephritic glomeruli by 96%, without affecting macrophage accumulation or systemic indices of coagulation. Anti-TF antibody significantly reduced glomerular fibrin deposition (fibrin scores, 0.43 +/- 0.10 (treated) and 1.40 +/- 0.19 (control); P < 0.0005), crescent formation (0.33 +/- 0.05 (treated) and 1.0 +/- 0.06 (control); P < 0.0005), and development of renal failure (serum creatinine, 168 +/- 22 mumol/l (treated) and 267 +/- 35 mumol/l (control); P < 0.04). This was associated with significant reduction in proteinuria (1189 +/- 277 mg/24 hours (treated) and 2060 +/- 336 mg/24 hours (control); P < 0.03) and expression of MHC class II antigen in glomeruli (1.25 +/- 0.41 (treated) and 2.83 +/- 0.53 (control); P < 0.03) and in tubules and interstitial areas. These data demonstrate that TF is the major in vivo initiator of fibrin deposition in crescentic GN. The reduction in proteinuria and glomerular major histocompatibility class II antigen expression by TF inhibition suggests that TF may also activate other mediators that contribute to glomerular injury.

Topics: Animals; Antibodies; Blood Coagulation; Fibrin; Glomerulonephritis; Histocompatibility Antigens Class II; Immunoconjugates; Kidney Glomerulus; Male; Proteinuria; Rabbits; Renal Insufficiency; Thromboplastin

The plasminogen/plasmin system has the potential to affect the outcome of inflammatory diseases by regulating accumulation of fibrin and other matrix proteins. In human and experimental crescentic glomerulonephritis (GN), fibrin is an important mediator of glomerular injury and renal impairment. Glomerular deposition of matrix proteins is a feature of progressive disease. To study the role of plasminogen and plasminogen activators in the development of inflammatory glomerular injury, GN was induced in mice in which the genes for these proteins had been disrupted by homologous recombination. Deficiency of plasminogen or combined deficiency of tissue type plasminogen activator (tPA) and urokinase type plasminogen activator (uPA) was associated with severe functional and histological exacerbation of glomerular injury. Deficiency of tPA, the predominant plasminogen activator expressed in glomeruli, also exacerbated disease. uPA deficiency reduced glomerular macrophage infiltration and did not significantly exacerbate disease. uPA receptor deficiency did not effect the expression of GN. These studies demonstrate that plasminogen plays an important role in protecting the glomerulus from acute inflammatory injury and that tPA is the major protective plasminogen activator.

Topics: Animals; Fibrin; Glomerulonephritis; Kidney; Kidney Glomerulus; Mice; Mice, Mutant Strains; Plasminogen; Renal Insufficiency; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

Crescentic glomerulonephritis (GN) has immunopathological features of delayed type hypersensitivity (DTH) and results from a T helper cell 1 (Th1) dependent immune response. The current study examined the capacity of Th2 cytokines, interleukin (IL)-4 and IL-10, to alter the outcome of crescentic GN, after injury is established. Sensitized, control treated mice developed crescentic GN with functional renal injury (117 +/- 20 microliters/min, normal mouse 182 +/- 8 microliters/min, P < 0.05) 10 days after an i.v. dose of sheep anti-mouse glomerular basement membrane globulin. Combined treatment with IL-4 and IL-10 starting three days after initiation of disease significantly reduced glomerular crescent formation (5.3 +/- 3.2%, control treatment 23.3 +/- 6.4%, P < 0.02) and preserved renal function (165 +/- 15 microliters/min, P = 0.57 compared to normal mice). Treatment with IL-4 alone did not reduce crescent formation or protect renal function. Mice treated with IL-10 showed trends to decreased crescent formation and preservation of renal function. In all cytokine treated groups, the accumulation of effectors of glomerular injury (CD4+ positive T cells, macrophages and fibrin) was reduced, with the combination treatment having the greatest effect. Administration of Th2 cytokines, IL-4 and IL-10 to mice with established GN attenuates the development of glomerular crescent formation and protects renal function.

Topics: Animals; Creatinine; Fibrin; Glomerulonephritis; Hypersensitivity, Delayed; Interferon-gamma; Interleukin-10; Interleukin-4; Kidney; Macrophages; Male; Mice; Mice, Inbred C57BL; Proteinuria; Recombinant Proteins; T-Lymphocytes

We have recently developed a model of thrombotic microangiopathy with injury to the glomerular endothelial cell (GEN) induced by heterologous antibody to rat GEN. In addition to GEN injury rats developed glomerular platelet aggregation and fibrin deposition, acute renal failure, and acute tubular necrosis with interstitial inflammation. To study the role of complement in mediating this lesion, we induced the disease in normal complement PVG rats and measured the effects of generalized complement depletion with cobra venom factor (CVF) and of selective C6 deficiency using genetically C6 deficient PVG animals. Complement sufficient rats developed severe endothelial injury accompanied by platelet aggregation, fibrin deposition, decrease in endothelial cells assessed by antibody staining in the glomerulus, and macrophage infiltration. These changes were associated with marked reduction in renal function. These features were either absent or markedly diminished in complement depleted or C6 deficient rats. This demonstrates that C5b-9, the terminal product of activation of the complement cascade, plays an important role in the pathogenesis of this immune renal microvascular endothelial injury model. Thus, the complement system may play a pathogenic role in renal microvascular diseases such as thrombotic microangiopathy.

Topics: Acute Kidney Injury; Animals; Blood Platelets; Complement C3; Complement C6; Complement Hemolytic Activity Assay; Complement Membrane Attack Complex; Disease Models, Animal; Endothelium; Fibrin; Glomerulonephritis; Immunoglobulin G; Kidney Glomerulus; Macrophages; Male; Microcirculation; Microscopy, Electron; Rats; Rats, Inbred Strains

Tissue factor pathway inhibitor (TFPI) was demonstrated in the kidneys of normal rabbits and in a crescentic model of glomerulonephritis (GN), where fibrin is a key mediator of injury. In normal kidneys, TFPI was expressed in glomeruli, in intrarenal arteries and the interstitial capillary network. Evidence for TFPI synthesis in vivo was provided by in situ demonstration of TFPI mRNA in glomeruli and intrarenal vessels and by biosynthetic labeling of TFPI released from glomeruli in vitro. In fibrin-dependent crescentic GN, glomerular TFPI synthesis and expression was initially decreased (TFPI antigen at 24 h, 7.5 +/- 0.7 ng/10(3) glomeruli; normal, 11.1 +/- 0.9 ng/10(3) glomeruli, P < 0.02) and subsequently returned to normal values. Plasma TFPI levels increased progressively throughout the evolution of disease. In vivo inhibition of TFPI using an anti-TFPI antibody during the development of GN significantly increased glomerular fibrin deposition (GFD) and exacerbated renal impairment. Infusion of recombinant human TFPI significantly reduced development of GFD (fibrin scores, TFPI treated 0.82 +/- 0.11, control 1.49 +/- 0.14, P < 0.01), proteinuria and renal impairment. This data indicates that TFPI is synthesized and expressed in normal glomeruli and is down regulated in the early response to glomerular injury. Endogenous glomerular TFPI and treatment with recombinant TFPI reduces GFD and injury in fibrin dependent GN. TFPI has the potential to be of therapeutic benefit in the management of fibrin dependent human GN.

Topics: Animals; Anticoagulants; Fibrin; Gene Expression; Glomerulonephritis; Humans; Kidney; Kidney Glomerulus; Lipoproteins; Male; Rabbits; Recombinant Proteins; Reference Values; RNA, Messenger; Transcription, Genetic

For the first time, a functional thrombin receptor has been found in human glomeruli by immunohistochemistry using a specific monoclonal antibody directed against extracellular N-terminus. This receptor is constitutively expressed in normal human kidney. The 3 glomerular cell types, endothelial, mesangial and epithelial cells, are positively stained as are the endothelial cells of renal arteries. By in situ hybridization using a digoxigenin-labelled cDNA probe specific for thrombin receptor, the thrombin receptor mRNA was found to have the same distribution. A lighter staining of glomerular endocapillary cells was observed in cases of thrombotic microangiopathy and extracapillary glomerulonephritis. 2 renal diseases associated with in situ thrombin generation and fibrin formation whereas by in situ hybridization, the thrombin receptor mRNA was overexpressed. To understand the discrepancy between the surface expression of thrombin receptor antigen in normal and fibrin-related glomerulopathies, we studied the internalization of thrombin receptor in human mesangial cells. We found that thrombin and thrombin agonist peptides induce homologous internalization of thrombin receptor in a dose-dependent manner. In addition, a dose-dependent loss of cell surface thrombin receptor is induced by phorbol-12-myristate-13-acetate (PMA), suggesting that thrombin receptor undergoes heterologous internalization in response to PMA. The homologous internalization of the thrombin receptor is not mediated by protein kinase C activation. Taken together, the results suggest that thrombin receptor is internalized through at least 2 different pathways.

Topics: Case-Control Studies; Fibrin; Glomerulonephritis; Humans; Receptors, Thrombin; Thrombin

CD59 is a molecule which is present on the host cell membranes and inhibits formation of membrane attack complex. A monoclonal antibody, 6D1, recognizes a rat analogue of human CD59. 6D1 inhibits function of rat CD59 and can enhance complement-mediated hemolysis in vitro. To assess the role of CD59 in complement-mediated glomerular injury, 6D1 was tested in a model of experimental glomerulonephritis induced by a lectin and its antibodies. The left kidney of a rat was perfused either with 200 micrograms of Lens culinaris hemagglutinin (LCH) plus 1 mg of 6D1 (IgG1 fraction) (Group I and III) or with LCH only (Group II) through a cannula placed in the left renal artery. All the perfusate was discarded from a cannula in the renal vein. The holes in the artery and vein were repaired by microsurgery and the blood circulation was re-established. Rats were injected either with 0.125 ml of rabbit anti-LCH serum (Group I and II), or with normal rabbit serum (Group III) via tail vein one minute after the recirculation. Fifteen minutes after injection, significant C9 deposition in the glomeruli was observed only in Group I, whereas C3 deposition in Group I and II were comparable. At Day 4, total glomerular cells, proliferating cells, glomerular expression of intercellular adhesion molecule-1 and fibrin deposition in Group I were all significantly increased when compared with Group II. At Day 7, number of total glomerular cells and leukocytes in the glomeruli of Group I were significantly higher than in Group II. The glomeruli in Group III appeared normal throughout experiments. These data indicate that the functional inhibition of a rat analogue of human CD59 worsens complement-mediated glomerular injury in vivo.

Topics: Animals; Antigens, CD; CD59 Antigens; Complement C3; Complement C9; Complement Inactivator Proteins; Disease Models, Animal; Female; Fibrin; Glomerulonephritis; Intercellular Adhesion Molecule-1; Kidney Glomerulus; Lectins; Membrane Glycoproteins; Plant Lectins; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar

We have established a recombinant inbred strain of mouse named spontaneous crescentic glomerulonephritis-forming mouse/Kinjoh or SCG/Kj. Mice of this strain spontaneously develop rapidly progressive glomerulonephritis. This strain of mice was derived from (BXSB/Mp x MRL/Mp-lpr/lpr)F1 hybrid mice by brother x sister mating coupled with repeated histopathologic selection for breeding of mice whose parents had the highest frequency of crescent formation in the kidneys. In this strain of mice, nephritis appears earlier and is more rapidly progressive than in any other murine model of systemic lupus erythematosus. Histopathologically, the characteristic renal lesions in the mice of this strain express a most dramatic form of crescentic glomerulonephritis. The lesions in the kidneys show only slight fine granular immune deposits along the glomerular basement membrane associated with remarkable extraglomerular proliferation and hemorrhage in Bowman's space. Although selection was not based on vasculitis, mice of this strain also exhibit a high incidence of necrotizing vasculitis. These vascular lesions involve primarily small arteries and arterioles and many organs and tissues but spare the kidneys. Thus this form of vasculitis has been found to be correlated with the crescentic form of glomerulonephritis but not with lymphoid hyperplasia of the spleen. We conclude that, in this strain of mouse, the rapidly progressive glomerulonephritis is genetically restricted and that this genetic restriction is firmly linked to that responsible for the vasculitis.

Topics: Animals; Chromosome Mapping; Coronary Circulation; Crosses, Genetic; Female; Fibrin; Glomerulonephritis; Immunohistochemistry; Kidney; Male; Mice; Mice, Inbred Strains; Ovary; Proteinuria; Selection, Genetic; Sex Factors; Species Specificity; Spleen; Stomach; Vasculitis

We carried out an immunohistochemical study of tissue-type plasminogen activator (PA) and urokinase-type PA, and their inhibitors, PA inhibitor-1 and PA inhibitor-2, using renal biopsy specimens obtained from 86 patients with various forms of glomerulonephritis. The controls were four normal renal tissue specimens. On immunofluorescent observation, granular staining for tissue-type PA was found to be distributed along the glomerular capillary walls. The fluorescence was weak in the normal renal tissue and occasionally intense in the tissues of patients with IgA nephritis, minimal change nephrotic syndrome, and lupus nephritis. PA inhibitor-1 was abundant in the glomerular epithelial cells and scarce in the mesangial area and glomerular capillary lumens of the normal renal tissues. This was confirmed by immunoelectron microscopy using gold staining. The fluorescence of PA inhibitor-1 was weaker in some specimens of nephritic tissues than in the normal renal tissues. Urokinase-type PA and PA inhibitor-2 were negative within the glomeruli in all the specimens. In the glomerulonephritic tissues which were fibrin deposition-positive, tissue-type PA expression in the glomeruli tended to be strong. An association between fibrin deposition and PA inhibitor-1 staining was not clear. These data suggest that expression of tissue-type PA in the glomeruli increases in association with fibrin deposition.

Topics: Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Microscopy, Immunoelectron; Plasminogen Inactivators; Staining and Labeling; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

To evaluate the suggested imbalance between coagulation and fibrinolysis in the development of glomerulonephritis, plasminogen activator inhibitor (PAI) activity was studied in the plasma of rats with nephrotoxic nephritis. PAI activity rose within 1 h of the injection of nephrotoxic globulin (NTG), peaked at 2 h and returned to the normal range within 24 h. PAI activity was dependent on the dose of NTG and increased significantly during passage through the kidney. PAI activity was also detected in the culture supernatant from isolated glomeruli with nephrotoxic nephritis. Intracapillary fibrin deposits were formed within 2 h; their numbers increased gradually over 24 h. Tumor necrosis factor (TNF) also induced a progressive increase in PAI activity in normal rats. The injection of TNF to rats with NTG synergistically accelerated both the increase in PAI activity and the prevalence of fibrin deposits. These results suggest that PAI may be released from the glomeruli affected by nephrotoxic nephritis and imply that PAI may play a role in the local coagulation in the capillaries of the nephritic kidneys, although this is probably not the only mechanism which explains the continued formation of the glomerular fibrin deposits.

Topics: Animals; Blood Coagulation; Female; Fibrin; Fibrinolysis; Glomerulonephritis; Kidney Glomerulus; Kinetics; Plasminogen Inactivators; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

It is a well known fact that intraglomerular coagulation plays an important role in the development of human primary glomerular diseases. However, the precise mechanism of intraglomerular coagulation, and intraglomerular coagulability and/or fibrinolytic activity remains obscure. The present study was aimed to elucidate the role of the intraglomerular coagulation and fibrinolysis in human primary glomerular diseases. Subjects enrolled in this study were 27 patients with minimal change nephrotic syndrome (MCNS), 14 patients with focal glomerular sclerosis (FGS), 36 patients with membranous nephropathy (MN), 161 patients with mesangial proliferative glomerulonephritis (mesPGN), 9 patients with membranoproliferative glomerulonephritis (MPGN), and 40 healthy volunteers as controls. Normal human renal cortex as controls of isolated intraglomerular plasminogen activator activity (PAA) was obtained at the time of nephrectomy from the normal pole of kidneys removed because of an opposite pole tumor. Urinary urokinase (UK), fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (B beta 15-42) antigens were measured by RIA. Urinary tissue plasminogen activator (t-PA) antigen was measured by ELISA. Urinary fibrin/fibrinogen degradation products (FDP) were measured by latex agglutination method. Moreover, PAA was measured by 125I-fibrin films. The following results were obtained: 1) In primary glomerular diseases, levels of urinary UK and t-PA were significantly lower than those in healthy volunteers, 2) Urinary UK and t-PA showed gradual decrease along with the development of mesangial proliferation, 3) Urinary UK and t-PA were significantly correlated with both the urinary FPA and B beta 15-42, 4) In mesPGN and FGS, PAA was significantly lower than that in normal controls, 5) PAA was significantly correlated with urinary UK, t-PA, FPA and B beta 15-42, 6) Urinary UK and t-PA in the patients with urinary FDP were significantly lower than those in patients without urinary FDP, 7) Urinary UK, t-PA and PAA were significantly lower in patients with intraglomerular fibrin deposition than those in patients without fibrin depositions. These findings suggest that the decrease of urinary UK and t-PA levels and the diminution of isolated intraglomerular plasminogen activator activity contribute to the progression of primary glomerular diseases.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Female; Fibrin; Fibrinolysis; Glomerulonephritis; Humans; Kidney Glomerulus; Male; Middle Aged; Plasminogen Activators; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

Twelve miniature pigs were inoculated with an attenuated African swine fever virus to study glomerular involvement in surviving pigs. In acute phase, kidneys were severely affected and displayed a glomerular capillary thrombosis with fibrin deposition in vascular lumen, detected by immunofluorescence. Fibrin-positive deposits were progressively cleared between one to three months after infection in surviving pigs. The histological picture in kidneys of surviving pigs, up to one post-infection year, showed a focal and segmental glomerulonephritis with hyalinosis, and IgM and C3 deposition was detected by immunofluorescence. Its pathogeny as an evolutive stage of acute glomerular injury is pointed out.

Topics: African Swine Fever; Animals; Antibodies; Antigen-Antibody Complex; Complement C3; Fibrin; Glomerulonephritis; Immunoglobulin M; Immunohistochemistry; Kidney Glomerulus; Swine; Viremia

Leflunomide (HWA 486, a novel isoxazol derivative), shown to have potent immunosuppressant and antiinflammatory effects, was evaluated for its inhibitory and therapeutic effects on the glomerulonephritis induced in rats by rabbit antiserum against rat glomerular basement membrane. Leflunomide was administered orally to rats at 0.5 and 2 mg/kg/day for 20 days from 2 days before injection of the rabbit antiserum and at 2 mg/kg/day for 14 days from 5 days after the antibody injection. The present study consisting of 2 experiments for inhibitory (I) and therapeutic (II) effects of leflunomide revealed the following effects at 2 mg/kg: in experiment I, significant decreases in (a) urinary total protein, (b) plasma total cholesterol and fibrinogen and (c) thymus weight, and decreased incidences of fibrin deposits in Bowman's space, adhesion of the glomerulus to Bowman's capsule and deposition of rat IgG and C3; and in experiment II, decreases in (a), (b) and (c), though smaller than in experiment I, and decreases deposition of rat C3. Thus, leflunomide had potent inhibitory and limited therapeutic effects on glomerulonephritis, suggesting that the compound is effective in inhibiting the onset and development of glomerulonephritis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Basement Membrane; Cell Division; Complement C3; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Immune Sera; Immunoglobulin G; Immunosuppressive Agents; Isoxazoles; Kidney Glomerulus; Leflunomide; Male; Periodic Acid-Schiff Reaction; Proteinuria; Rats; Rats, Inbred Strains

This paper describes the results of experiments designed to investigate the role of oxygen radicals in the pathogenesis of rat experimental glomerulonephritis. Generation of oxygen radicals was induced by phorbol ester in rats with Masugi nephritis, aminonucleoside nephrosis and streptozotocin-induced diabetes mellitus. Marked formation of fibrin thrombi was observed in the glomerular capillaries during the heterologous phase of Masugi nephritis, but not during the autologous phase. Induction of fibrin thrombi was also seen in nephrotic rats which had received the aminonucleoside, puromycin, but not in diabetic rats. These results suggest that in Masugi nephritis, oxygen radicals may be related to the formation of fibrin thrombi. Neutrophils seem to be of importance in the pathogenesis of such lesions.

Topics: Animals; Fibrin; Free Radicals; Glomerulonephritis; Male; Neutrophils; Oxygen; Rats; Rats, Inbred Strains; Tetradecanoylphorbol Acetate; Thrombosis

Fibrin deposition is prominent in delayed-type hypersensitivity (DTH) reactions and is initiated by antigen-specific, T-lymphocyte-directed macrophage expression of human tissue factor (HTF). To examine the role of DTH in glomerular fibrin deposition, 10 fibrin-positive and 24 fibrin-negative biopsy specimens from patients with glomerulonephritis (GN) and samples from normal controls were studied with monoclonal antibodies against T cells, macrophages, and HTF. Fibrin-positive sections showed intense glomerular staining for HTF and significantly more T cells and macrophages than fibrin-negative specimens. All the essential elements of DTH reactions can therefore be simultaneously demonstrated within glomeruli from patients with fibrin-related GN. These findings suggest a role for cell mediated immunity in GN.

Topics: Adolescent; Adult; Aged; Factor VIII; Female; Fibrin; Glomerulonephritis; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Macrophages; Male; Middle Aged; T-Lymphocytes; Thromboplastin

Glomerular fibrin deposition and augmentation of procoagulant activity (PCA) are dependent on glomerular macrophage infiltration in anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) in rabbits. Expression of PCA on the surface of glomerular macrophages and/or augmentation of intrinsic glomerular cell PCA by macrophage cytokines (such as IL 1) are potential mechanisms by which macrophages may augment glomerular PCA. Macrophages were isolated from glomeruli of rabbits developing anti-GBM GN to measure their PCA expression. These macrophages were characterized by morphological and functional criteria. Glomerular macrophages expressed markedly augmented PCA (2.8 +/- 0.7 mU/10(3) cells) compared with blood monocytes (0.05 +/- 0.02 mU/10(3) cells) and alveolar macrophages (0.09 +/- 0.02 mU/10(3) cells) from the same rabbits. Glomerular macrophage PCA was functionally identical to the PCA of whole glomeruli, and was consistent with that of tissue factor. Supernatants from nephritic glomeruli contained IL 1 bioactivity and augmented endothelial cell PCA in vitro. However, these supernatants and purified IL 1 failed to augment the PCA of normal and macrophage-depleted nephritic glomeruli. These studies demonstrate that, in this model of anti-GBM GN, glomerular macrophages contribute directly to the augmented glomerular PCA by their expression of surface membrane PCA, and have the potential to indirectly augment glomerular PCA by their production of cytokines capable of enhancing endothelial cell PCA.

Topics: Animals; Blood Coagulation Factors; Cell Separation; Cell-Free System; Fibrin; Glomerulonephritis; Kidney Glomerulus; Monocytes; Pulmonary Alveoli; Rabbits

Topics: Blood Coagulation; Blood Coagulation Factors; Fibrin; Fibrinolysis; Glomerulonephritis; Humans; Kidney Glomerulus; Platelet Aggregation

Blood coagulation function was serially studied in 84 children with nephrotic syndrome. Fifty-eight had minimal change disease, six had focal glomerulosclerosis and 20 had other forms of renal disease associated with the nephrotic syndrome. Qualitatively similar abnormalities in fibrinogen metabolism were present in all groups with clinically overt nephrotic syndrome; plasma fibrinogen concentration and high molecular weight fibrin(ogen) complexes (HMWFC) were grossly elevated (P less than 0.001 in most groups). With disease remission fibrinogen and HMWFC concentrations decreased to the normal range, usually with concomitant transient increase in plasma fibrinolytic activity (P less than 0.02). Alterations in concentrations of other proteins involved in coagulation and fibrinolysis differed depending on the underlying cause for the nephrotic syndrome. Antithrombin III concentration was normal except in the focal glomerulosclerosis group. The results demonstrate that a coagulopathy characterized by pathological degree of thrombin action on fibrinogen complicates the nephrotic state and may be initiated by different mechanisms. It is suggested that this coagulopathy, which remits with clinical improvement, is consequent upon local intrarenal activation of the blood coagulation system.

Topics: Adolescent; alpha 1-Antitrypsin; alpha-Macroglobulins; Antithrombin III; Blood Coagulation Disorders; Child; Child, Preschool; Factor XIII; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Molecular Weight; Nephrosis, Lipoid; Nephrotic Syndrome

The mechanism involved in glomerular fibrin deposition was investigated during mercuric chloride (HgCl2)-induced autoimmune glomerulonephritis in the Brown Norway rat. To ascertain whether the local hemostatic system was activated secondarily to the immunological conflict, the ability of glomerular lysates to induce coagulation in vitro was assessed in treated and control rats. Glomerular procoagulant activity (PCA) of HgCl2-injected rats was measured on day 12 (latent phase of the disease), day 20 (acme), and days 32 and 42 (recovery phase) after the first mercury injection. PCA rose 3-fold (p less than 0.02) at day 20 and then almost returned to control values. Proteinuria, PCA, and the incidence of glomerular fibrin deposits peaked concomitantly at day 20. Glomerular PCA was characterized as thromboplastin. The number of Ia positive cells detected by monoclonal OX-6 antibody was not different from the control number at any phase of the disease; the number of macrophages per glomerular section detected by electron microscopy at day 20 in HgCl2-injected rats was 1.80 +/- 0.60, versus 0.30 +/- 0.11 in the controls. No correlation was found between glomerular PCA and either the number of monocytes/macrophages or of Ia-positive cells present in the glomeruli. Since glomerular PCA was maximal at the onset of fibrin formation in the glomeruli and then decreased toward its basal level, and since the fibrin disappeared, it is concluded that increased production of thromboplastin by glomeruli, with activation of the extrinsic coagulation pathway, may contribute to intraglomerular fibrin deposition in HgCl2-induced glomerulonephritis.

Topics: Animals; Autoimmune Diseases; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Glomerulonephritis; Histocompatibility Antigens Class II; Kidney Glomerulus; Macrophages; Male; Mercuric Chloride; Proteinuria; Rats; Rats, Inbred BN; Thromboplastin

The concentration of urinary fibrin(ogen) degradation products (FDP) was determined by using enzyme immunoassay and radio immunoassay, and their urinary levels were compared with histologically classified types of glomerulonephritis. Urinary FDP levels were higher in the severe type of proliferative glomerulonephritis and at the active phase of systemic lupus erythematosus (SLE). They were also high in the membranous glomerulonephritis. Molecular weight of urinary FDP of a patient with severe proliferative glomerulonephritis was determined to be 150,000 and 68,000, respectively after gel filtration. Urinary FDP levels were higher in patients with glomerular fibrin deposit than in patients without fibrin deposit or normal volunteers. The amounts of excreted protein in urine was not related to the amounts of FDP. Decrease in the reciprocal of serum creatinine levels resulted in high urinary FDP levels, indicating that high urinary FDP levels may represent deterioration of renal function.

Topics: Chromatography, Gel; Chronic Disease; Creatinine; Fibrin; Fibrin Fibrinogen Degradation Products; Glomerulonephritis; Humans; Immunoassay; Molecular Weight

Topics: Animals; Anticoagulants; Fibrin; Glomerulonephritis; Humans; Inflammation; Macrophages; Microcirculation; Monocytes; Rabbits; Rats; Thromboplastin

Although the glomerulonephritis (GN) and renal vasculitis in polyarteritis nodosa (PAN) are generally considered to be immune-mediated, the pathogenesis of the renal injury and the role of immune complex (IC) deposition are unclear. To better define the nature of the glomerular and vascular injury in PAN, we performed a detailed ultrastructural study of 27 renal biopsies from 20 patients with histologically confirmed PAN of the microscopic or overlap (microscopic/macroscopic) type. A total of 48 arteries and arterioles were studied ultrastructurally, including 20 vessels with recognizable vasculitis in 1 micron-thick survey sections. By immunofluorescence, glomerular and vascular immunoglobulin deposits were generally scanty, primarily located in areas of necrosis or sclerosis. Fibrinogen, C3 and C1 were more commonly detected, often in the absence of demonstrable immunoglobulin. By electron microscopy, discrete electron-dense deposits of probable immune-type were found in the glomeruli of five initial biopsies. No electron-dense deposits were identified in any of the arteries or arterioles studied. In both glomeruli and vessels, endothelial injury and subendothelial fibrin deposition were the earliest detectable ultrastructural changes. The pathogenetic implications of these findings are discussed.

Topics: Adult; Aged; Antigen-Antibody Complex; Biopsy; Child; Female; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunoglobulins; Kidney Glomerulus; Male; Microscopy, Electron; Middle Aged; Polyarteritis Nodosa; Renal Artery; Renal Veins

Crescentic glomerulonephritis was induced in the rabbit with two intravenous injections of goat nephrotoxic serum (NTS). Prominent proliferative glomerulonephritis, characterized by intracapillary as well as extracapillary emigration of monocytes and fibrin deposition, developed 7 days after the first injection. The changes rapidly progressed to crescent formation. In order to observe alterations of the glomerular basement membrane (GBM) related to crescent formation, unfixed, isolated glomeruli were treated with Triton X-100. The GBM thus denuded was shown to have a number of microperforations, which subsequently became much larger holes or fissures. It is suggested that monocytes and fibrin deposits may play a role in the induction of the GBM change.

Topics: Animals; Basement Membrane; Fibrin; Glomerulonephritis; Kidney Glomerulus; Male; Microscopy, Electron, Scanning; Monocytes; Rabbits

The temporal relationships of macrophage accumulation, glomerular fibrin deposition, the expression of glomerular procoagulant activity (PCA), and Factor VIII antigen deposition were studied in rabbits in which antiglomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) developed. The initiation of injury coincided with the accumulation of glomerular macrophages. Glomerular fibrin, assessed by immunofluorescence and by deposition of 125I-fibrinogen, paralleled the development of glomerular crescents and renal impairment. Macrophage ingress clearly preceded the deposition of 125I-fibrinogen within glomeruli. Augmented levels of PCA were present in glomeruli prior to the initiation of fibrin deposition, and peak levels coincided with the peak glomerular macrophage presence. Factor VIII related antigen was apparent late in the disease and was present mainly at the margins of fibrinous crescents. These data demonstrate that accumulation of glomerular macrophages precedes glomerular fibrin deposition in anti-GBM GN. The augmentation of PCA, coincident with the appearance of glomerular macrophages, suggests a role for macrophage PCA in the initiation of fibrin deposition within the glomerular tuft in this model.

Topics: Animals; Factor VIII; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Macrophages; Male; Models, Biological; Rabbits

The effect of fibrinolysis with Streptokinase and defibrination with Ancrod on the progression of established fibrin-related glomerular injury was assessed in rabbits developing anti-glomerular basement membrane antibody-induced glomerulonephritis. Untreated rabbits developed renal failure and a severe crescentic nephritis with prominent fibrin deposition after 5 days. Rabbits with established injury and glomerular fibrin deposition were treated with Streptokinase or Ancrod over the last 4 days of this model. Both treatments resulted in significant protection from loss of renal function and reduced crescent formation by day 5. Glomerular fibrin deposition was also significantly reduced by both agents, although Streptokinase produced a greater reduction than Ancrod. Two further groups of rabbits with advanced disease, were treated over the last two days of this model. Although treatment reduced glomerular fibrin deposition, no protection from loss of renal function was observed. These studies indicate that both treatments were effective, if used early, in preserving renal function in established fibrin related glomerulonephritis, but they did not effect the outcome of more advanced disease. Both agents prevented further glomerular fibrin deposition, although only early treatment with Streptokinase reduced glomerular fibrin to below pre-treatment levels.

Topics: Ancrod; Animals; Complement C3; Creatinine; Fibrin; Fibrinogen; Glomerulonephritis; Immunoglobulin G; Kidney Glomerulus; Rabbits; Streptokinase

Topics: Blood Coagulation Factors; Fibrin; Glomerulonephritis; Humans; Renal Artery Obstruction; Thrombosis

Renal biopsies from 44 patients with steroid sensitive nephrotic syndrome were examined with respect to the content of their intraglomerular platelets and compared with 18 normal control patients and with 51 patients with membranous glomerulonephritis and the nephrotic syndrome. The results suggested that platelet activity was not involved in the pathogenesis of steroid sensitive nephrotic syndrome; in the active phase of the number of platelets in glomeruli is lower than that of normal controls, and this may be associated with increased sensitivity to aggregating agents as part of the nephrotic syndrome. After steroid treatment and disappearance of proteinuria, the number of intraglomerular platelets rises to normal values.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Blood Platelets; Child; Child, Preschool; Fibrin; Glomerulonephritis; Humans; Kidney Glomerulus; Microscopy, Electron; Middle Aged; Nephrosis, Lipoid

A telescoped model of nephrotoxic nephritis in the rabbit, using guinea pig antiglomerular basement membrane IgG in rabbits preimmunized with guinea pig IgG, reproducibly induced crescentic nephritis. Procoagulant activity (PCA) was measured in sieve-isolated glomeruli that had been either sonicated or cultured for 48 hours. In both sonicated and cultured glomeruli PCA peaked on days 5 and 6. The time course for appearance of PCA corresponded precisely with the appearance of proteinaceous material containing fibrin in Bowman's space as measured by a light microscopic histologic scoring system and confirmed by immunofluorescence and electron microscopy. Glomerular PCA returned to baseline by days 9 and 10 in spite of progression of glomerular injury. PCA also appeared in urine. Urine PCA peaked on day 8 and persisted through day 12 when glomerular PCA had returned to baseline. Glomerular and urine PCA were characterized using human coagulation factor-deficient plasmas and antithromboplastin IgG. Both glomerular PCA and urine PCA were inhibited by antithromboplastin IgG, showing that thromboplastin (tissue factor) contributed to PCA. The PCA in glomerular sonicates was dependent on factor X, but independent of factor VII or Hageman factor, suggesting that factor VII was present. Following glomerular culture for 48 hours the PCA had changed and in some cases was dependent on Hageman factor, factor IX, and factor VII for full PCA expression. Urine PCA was uniformly Hageman factor dependent and sometimes independent of factors VII and X. No active thrombin was present. The forms of glomerular and urine PCA were, therefore, complex. They seemed to be primarily driven by thromboplastin but also appeared to require the presence of the intrinsic coagulation pathway for full expression of PCA.

Topics: Animals; Basement Membrane; Blood Coagulation Factors; Disease Models, Animal; Fibrin; Glomerulonephritis; Immunoglobulin G; Kidney Glomerulus; Macrophages; Rabbits; Thromboplastin; Time Factors

Glomerular fibrin deposition is important in the pathogenesis of renal failure and crescent formation in glomerulonephritis. The mechanisms of glomerular fibrin deposition are unknown. The current studies explored the role of macrophages in this process. Methods were developed for measuring glomerular fibrin deposition and glomerular procoagulant activity in a passive model of the autologous phase of antiglomerular basement membrane antibody-induced glomerulonephritis in rabbits. Significant fibrin deposition was observed to be associated with glomerular macrophage accumulation. Leukocyte ablation with mustine hydrochloride prevented both glomerular macrophage accumulation and fibrin deposition without affecting the coagulation system or the deposition of disease-inducing antibodies and complement. Repletion with mononuclear inflammatory cells produced significant fibrin deposition. To examine the role of tissue injury per se in glomerular fibrin deposition, a macrophage-independent model of glomerular injury (heterologous phase glomerulonephritis) was also studied. Although a similar degree of glomerular injury occurred, there was no significant fibrin deposition. This suggests that macrophages, rather than injury alone, are responsible for fibrin deposition. Lysates of isolated glomeruli containing macrophages demonstrated greatly enhanced procoagulant activity compared with lysates of glomeruli without macrophages. Thus macrophages appear to be directly responsible for glomerular fibrin deposition in antiglomerular basement membrane antibody-induced glomerulonephritis, and this appears to be due to their ability to express procoagulant activity rather than their propensity to cause glomerular injury.

Topics: Animals; Basement Membrane; Blood Coagulation Tests; Disease Models, Animal; Fibrin; Glomerulonephritis; Immunization, Passive; Inflammation; Kidney Glomerulus; Lymphocyte Depletion; Macrophages; Mechlorethamine; Monocytes; Rabbits; Serum Sickness

Mercuric chloride (HgCl2) induces in Brown Norway (BN) rats an autoimmune disease characterized by a biphasic glomerulonephritis (GN). A transient nephrotic syndrome occurs during the third and fourth weeks after the first HgCl2 injection. Related to nephrotic syndrome, an hypercoagulable state develops with decreased factor XII and anti-thrombin III (AT III) levels and increased factor V activity and fibrinogen concentration. Moreover, during the same period, most of the rats were found thrombocytopenic. The presence of soluble fibrin monomer complexes and of fibrin degradation products (FDP) in the plasma of these rats associated with fibrin thrombi in glomerular capillary lumen proved the occurrence of disseminated intravascular coagulation (DIC). DIC was responsible for the death of several rats but most of these survived and clotting abnormalities were no longer found. Numerous factors can explain the occurrence of DIC in this model: anti glomerular basement membrane antibodies, circulating immune complexes, complement activation and/or glomerular endothelial cell detachment. The HgCl2 induced autoimmune disease appears as a good experimental model to study the relation between coagulation process and glomerulonephritis.

Topics: Animals; Autoimmune Diseases; Blood Coagulation; Disseminated Intravascular Coagulation; Female; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Hemostasis; Male; Mercuric Chloride; Mercury; Nephrotic Syndrome; Rats; Time Factors

Topics: Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Fibrinolysis; Glomerulonephritis; Hemostasis; Humans; Liver Cirrhosis; Postoperative Complications; Pulmonary Embolism; Thrombin; Thromboembolism; Thrombophlebitis

Injection of presensitized rats with goat antiserum to rat glomerular basement membrane (GBM) results in a crescentic glomerulonephritis with typical linear deposition of goat IgG and host IgG and C3 along the GBM. Sequential renal biopsies from rats with this model of anti-GBM nephritis were studied by light, electron, and immunofluorescence microscopy to investigate the mechanisms of crescent formation. The localization of fibrin-related antigens (FRA) and factor VIII-related antigens (VIIIAGN) at different stages of disease was specifically studied since earlier studies of human glomerulonephritis had shown deposits of FRA without VIIIAGN in crescents and suggested that either a thrombin-independent mechanism might cause fibrin deposition or, alternatively, that glomerular fibrinolysis was relatively deficient within Bowman's space. Separation of the endothelium from the GBM or glomerular endothelial loss was the first change noted, a lesion that promotes intracapillary FRA deposition. Subsequently, intracapillary hypercellularity and GBM damage became progressively more severe. During the second and third weeks, coincident with early crescent formation, increasing amounts of FRA were noted within Bowman's space; FRA in crescents persisted throughout the study, whereas FRA within the glomerular tuft decreased over time. In early lesions, granular deposits of IgM and factor VIIIAGN were found diffusely within crescents. However, at later times, extracapillary deposits of these proteins and IgG were limited to the periphery of crescents within the markedly thickened and altered Bowman's capsule. Persistence of IgM and factor VIIIAGN at the periphery of older crescents appears to result from entrapment in areas less subject to cellular degradation and transport. Preferential clearance of FRA from the glomerular tuft suggests that fibrinolysis is less effective in Bowman's space than clearance mechanisms within glomerular capillaries.

Topics: Animals; Antigens; Basement Membrane; Biopsy; Factor VIII; Female; Fibrin; Fibrinolysis; Fluorescent Antibody Technique; Glomerulonephritis; Kidney; Microscopy, Electron; Rats; Rats, Inbred Strains; Thrombin; von Willebrand Factor

Topics: Animals; Antigens; Disease Models, Animal; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Heparin; Humans; Kidney Glomerulus; Rats; Urokinase-Type Plasminogen Activator

Glomerular localization of Hageman factor and fibrin-related antigen (FRA) was examined in 31 cases of IgA nephropathy by immunofluorescent techniques. Hageman factor was observed in 21 cases (68%) and FRA in 24 cases (77%). It is suggested that blood coagulation occurs and fibrin is formed in the glomerulus of IgA nephropathy.

Topics: Antigens; Factor XII; Fibrin; Glomerulonephritis; Humans; Immunoglobulin A; Kidney Glomerulus

Topics: Fibrin; Fibrinogen; Glomerulonephritis; Humans; Immunoglobulin A; Kidney Glomerulus; Urokinase-Type Plasminogen Activator

Although acute infection with murine cytomegalovirus (MCMV) resulted in a transient focal glomerulonephritis characterized by mesangial inclusions, infection of HA/ICR mice given antilymphocyte globulin (ALG) led to progressive glomerulonephritis and renal failure. ALG alone without virus failed to produce progressive renal disease. Mice given both MCMV and ALG developed severe proteinuria and azotemia with glomerular crescents by 30 days. By immunofluorescence, viral antigen was limited to mesangial zones and glomerular axial poles. Granular deposits of rabbit IgG from ALG, mouse IgG, and C3 along the peripheral glomerular capillary walls were first observed 12 days after infection. By electron microscopy, virus was found only in glomerular mesangial cells that resembled macrophages. Intramembranous and subepithelial deposits in peripheral capillary walls were associated with accumulations of polymorphonuclear leukocytes dissecting into glomerular basement membranes. These observations best fit a multiphasic mechanism of glomerular injury initiated by persistent virus in the mesangium, followed by deposits of rabbit IgG from ALG, mouse IgG, and C in the peripheral capillary walls, resulting in an amplified immune-complex-mediated injury. Because other viruses localize within the glomerular mesangium, viruses should be considered potential causes of mesangial injury and progressive glomerulonephritis.

Topics: Animals; Antigens, Viral; Antilymphocyte Serum; Blood Urea Nitrogen; Complement C3; Cytomegalovirus Infections; Disease Models, Animal; Female; Fibrin; Glomerulonephritis; Immunoglobulin G; Kidney Function Tests; Kidney Glomerulus; Mice; Mice, Inbred ICR; Proteinuria; Rabbits

Analysis of 80 cases of SLE with renal involvement revealed the following. Angiitis involving arterioles and interlobular arteries was observed in 17 out of 42 cases with diffuse proliferative lupus GN. This was not observed in other types of lupus GN. Out of 17 cases of angiitis, 7 were complicated by thrombosis. Irregular deposits of immunoglobulins and complement were demonstrated in the vessel walls and in luminal thrombi and suggested an immune-complex origin. Fibrinogen was also demonstrable frequently. The vascular lesions were associated with severe glomerular and tubulointerstitial injury and a poor prognosis. A relatively favorable outcome was observed in SLE without renal angiitis.

Topics: Arteritis; Complement C3; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunoglobulins; Kidney; Lupus Erythematosus, Systemic; Microscopy, Electron; Prognosis

Urinary casts from 46 healthy volunteers and 60 patients with glomerulonephritis were examined for the presence of Tamm-Horsfall glycoprotein and other proteins. All samples gave immunofluorescence evidence of Tamm-Horsfall protein in casts. Casts from 59 of the patients but only three of the controls contained other proteins in addition (p less than 0.001). Immunoglobulins (IgG, IgM, IgA) were detected in casts from 53 of the patients but none of the healthy volunteers. Examination of urinary casts for immunoglobulins, complement, and fibrin provides a non-invasive method for distinguishing patients with active glomerular disease.

Topics: Complement Activating Enzymes; Complement C1q; Complement C3; Fibrin; Glomerulonephritis; Humans; Immunoglobulins; Mucoproteins; Proteinuria; Uromodulin

The localization of intrarenal cross-linked fibrin was examined by the effect of monochloroacetic acid treatment on the kidney sections. In acute glomerulonephritis or in mild diffuse or focal proliferative type of nephritis, cross-linked fibrin was observed mainly within glomerular capillary walls. Extension of cross-linked fibrin deposit over the mesangium or sclerotic area was seen in moderate to severe proliferative type of nephritis or in membranoproliferative glomerulonephritis. In hemolytic uremic syndrome or disseminated intravascular coagulation syndrome, cross-linked fibrin was detected within glomeruli and vessels.

Topics: Acetates; Child; Disseminated Intravascular Coagulation; Factor XIII; Fibrin; Glomerulonephritis; Hemolytic-Uremic Syndrome; Histocytochemistry; Humans; IgA Vasculitis; Immunoglobulin G; Kidney; Kidney Diseases; Nephrotic Syndrome; Tissue Distribution

The renal biopsies of 30 patients with rheumatoid arthritis and clinical evidence of renal disease were reviewed; only patients in whom the intravenous pyelogram was normal were subjected to biopsy, thus excluding those with papillary necrosis and chronic pyelonephritis. Tissue was studied by light, electron and immunofluorescence microscopy. There were 13 cases of mesangial change, 9 of membranous glomerulonephritis, 4 of tubulointerstitial change, 2 cases of focal segmental glomerulosclerosis, 1 case of amyloid and 1 of diffuse proliferative glomerulonephritis with crescents. All 9 patients with membranous glomerulonephritis but only 6 of 13 with mesangial change had received gold or penicillamine. We found no evidence of "glomerulitis" or of a rheumatoid vasculitis.

Topics: Adult; Aged; Arthritis, Rheumatoid; Biopsy; Complement C3; Female; Fibrin; Glomerulonephritis; Gold; Humans; Immunoglobulins; Kidney; Male; Microscopy, Electron; Middle Aged; Penicillamine

Topics: Adolescent; Adult; Aged; Blood Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Glomerulonephritis; Humans; Kidney Glomerulus; Male; Middle Aged

Topics: Animals; Fibrin; Glomerulonephritis; Indomethacin; Kidney Glomerulus; Muramidase; Prostaglandins; Rats; Rats, Inbred Strains; Urokinase-Type Plasminogen Activator

Ancrod, which produces in vivo defibrination, has been shown to improve renal function and decrease fibrin deposition and crescents in experimental glomerulonephritis. Ancrod was given for 14 days to 5 patients with glomerulonephritis, moderate to severe renal functional impairment, crescents, and/or fibrin deposition in glomeruli. 4 patients had systemic lupus erythematosus. Ancrod treatment resulted in fibrinogen levels less than 50 mg/dl without bleeding, decrease of previously elevated factor VIII and von Willebrand factor levels, and normalization of in vitro platelet hyperaggregation. Renal function improved in all 5 patients. Serial renal biopsies showed a relatively rapid decrease of glomerular thrombi and necrosis and little increase in glomerular sclerosis. Ancrod administration appears safe, and may have a role in treatment of certain types of glomerulonephritis.

Topics: Adolescent; Adult; Ancrod; Blood Coagulation; Factor VIII; Female; Fibrin; Fibrinogen; Glomerulonephritis; Humans; Kidney; Lupus Erythematosus, Systemic; Middle Aged; Platelet Aggregation; von Willebrand Factor

Topics: Acute Kidney Injury; Blood Platelets; Disseminated Intravascular Coagulation; Factor VIII; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Glomerulonephritis; Humans; Kidney Glomerulus; Platelet Aggregation; Prognosis

Topics: Animals; Endopeptidases; Fibrin; Glomerulonephritis; Nephritis; Rabbits; Urokinase-Type Plasminogen Activator

Topics: Child; Chromatography, Gel; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Glomerulonephritis; Hemolytic-Uremic Syndrome; Humans; Kidney Diseases; Kidney Glomerulus; Lupus Erythematosus, Systemic; Nephrotic Syndrome

Clinical and morphologic signs of intravascular coagulation have been studied in 63 patients with primary glomerulonephritis (GN) and in 19 patients with nephritis associated with systemic lupus erythematosus. A relationship between the frequency of fibrin deposition in the kidneys and severity of clinical signs and marked morphologic changes in GN has been revealed. Signs of local hypercoagulation are of prognostic significance. A more favourable prognosis is characteristic for patients who show nor fibrin deposition in the renal tissue and whose fibrinolytic system provides an adequate reaction.

Topics: Adolescent; Adult; Biopsy, Needle; Child; Child, Preschool; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinolysis; Glomerulonephritis; Humans; Immune Complex Diseases; Kidney; Lupus Erythematosus, Systemic; Male; Microscopy, Electron; Middle Aged; Nephritis

The state of thrombin-plasmin system was studied in 34 rabbits with Masuga nephritis untreated or treated with the use of heparin, urokinase, and uroplasmin. The untreated animals developed long-term activation of thrombinogenesis (hypercoagulation) with simultaneous inhibition of fibrinolysis accompanied by deposition of fibrin-postive substances in the lumens of capillaries and glomerular capsules, along basal membranes, and inside epithelial and endothelial cells. Heparin inoculated prophylactically prevented the development of nephritis and typical changes in the thrombin-plasmin system. Treatment with heparin, urokinase or uroplasmin produced regression of nephritis, elimination of fibrin-positive substances from the kidneys and gradual complete normalization of the functional status of the thrombin-plasmin system. It is suggested that not only heparin but also urokinase and uroplasmin can inhibit the immune process. The experimental results favours the immunocoagulation theory of nephritis pathogenesis.

Topics: Animals; Blood Coagulation; Endopeptidases; Fibrin; Fibrinolysin; Fibrinolysis; Glomerulonephritis; Heparin; Histocytochemistry; Immune Sera; Kidney; Kidney Glomerulus; Rabbits; Thrombin; Urokinase-Type Plasminogen Activator

A kidney and lung biopsy were performed on a patient with active Behçet's disease with renal and pulmonary involvement. Histologic, immunohistochemical and electron microscopic studies of the kidney biopsy specimen revealed a focal segmental necrotizing glomerulonephritis characterized by the presence of numerous subendothelial and occasional intramembranous deposits containing immunoglobulin G (IgG), the third component of complement (C3), the fourth component of complement (C4) and fibrin(ogen). Histologic and immunohistochemical studies of the lung biopsy specimen showed an acute venulitis and septal capillaritis associated with the presence of identical deposits within the walls of affected vessels. Circulating immune complexes were detected in the patient's serum by Raji cell assay. The findings indicate that the glomerulonephritis and pulmonary vasculitis occasionally occurring in Behçet's disease are due to the deposition of circulating antigen-antibody complexes. In addition, they strongly suggest that the majority of the major and minor manifestations of the disease, such as uveitis, cutaneous vasculitis, synovitis and meningoencephalitis, are a result of vascular immune complex deposition.

Topics: Behcet Syndrome; Capillaries; Complement C3; Complement C4; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immune Complex Diseases; Immunoglobulin G; Kidney Glomerulus; Lung; Middle Aged; Pulmonary Alveoli; Pulmonary Circulation; Vasculitis

The effects of platelet depletion with antibody have been studied in two models of the autologous phase of nephrotoxic nephritis in the rabbit. In the 'telescoped' model (animals pre-immunized to sheep IgG injected with sheep nephrotoxic antibody), platelet depletion did not alter intraglomerular fibrin deposition or evidence of glomerular damage, but did significantly reduce proteinuria during the first 3 days of the 5 day experiment. In the 'passive' model (animals injected with hyperimmune rabbit antiserum to sheep IgG 48 hr after sheep nephrotoxic antibody and killed 3 hr later), platelet depletion was associated with significantly fewer intraglomerular polymorphonuclear leucocytes (PMN), but again did not alter intraglomerular fibrin deposition. The results indicate that platelets are involved in the initiation of glomerular PMN localization in the autologous phase, but that fibrin-induced glomerular injury is platelet-independent.

Topics: Animals; Autoantibodies; Basement Membrane; Blood Cell Count; Blood Platelets; Complement C3; Creatinine; Disease Models, Animal; Fibrin; Glomerulonephritis; Immune Complex Diseases; Kidney Glomerulus; Leukocyte Count; Male; Neutrophils; Rabbits

Topics: Animals; Fibrin; Fibrinolysis; Glomerulonephritis; Immune Complex Diseases; Kidney Glomerulus; Plasminogen Activators; Rabbits

Topics: Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunoglobulin M; Kidney Diseases; Kidney Glomerulus; Lupus Erythematosus, Systemic; Urine

Topics: Bacteriological Techniques; Fibrin; Fibrin Fibrinogen Degradation Products; Glomerulonephritis; Hemagglutination Inhibition Tests; Humans; Staphylococcus aureus

Rats experimentally infected with Trypanosoma brucei rhodesiense developed a syndrome characterized by anemia, splenomegaly, and glomerulonephritis. Serologic evaluation revealed that the syndrome was accompanied by the presence of 3 autoantibodies--cold-active hemagglutinin, immunoconglutinin, and antibody to fibrinogen/fibrin products. Fluorescein isothiocyanate conjugated antibody tests showed the presence of fixed complement and fibrinogen on both trypanosomes and erythrocytes. All infected rats died by the ninth day of the infection with 5 animals showing signs of pulmonary involvement and shock. From these observations it is suggested that autoantigens, autoantibodies, and complement may have been causal in this syndrome.

Topics: Anemia; Animals; Antigen-Antibody Reactions; Autoantibodies; Complement Fixation Tests; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Hemagglutinins; Kidney; Male; Rats; Spleen; Splenomegaly; Syndrome; Trypanosomiasis, African

Recent studies in experimental crescentic glomerulonephritis, using the technique of glomerular culture, have shown that the macrophage is a major cell type present within the glomeruli and developing crescents. It has been suggested that their accumulation is a consequence of glomerular fibrin deposition. The effect of defibrination with ancrod on the cellular events occurring in experimental crescentic glomerulonephritis in the rabbit was therefore assessed in this disease using the techniques of culture of isolated glomeruli, electronmicroscopy or renal tissue, and light microscopy. Defibrinated animals developed only minimal renal impairment, virtually no fibrin deposition in Bowman's Space and only a mild degree of crescent formation, in contrast to the severe renal failure, fibrin deposition and crescent formation that occurred in the untreated animals. The culture of isolated glomeruli and electronmicroscopy of intact renal tissue demonstrated large numbers of macrophages within and emerging from glomeruli of both defibrinated and untreated animals. However, only in untreated animals were macrophages seen to migrate into Bowman's Space, phagocytose fibrin, transform into epithelioid cells and accumulate to form crescents. These studies suggest that fibrin deposition in Bowman's Space is the major stimulus to the macrophage migration from capillary loops and accumulation in Bowman's Space. However, fibrin deposition does not appear to be the stimulus to macrophage accumulation within capillary loops as this event was not affected by defibrination.

Topics: Animals; Culture Techniques; Female; Fibrin; Glomerulonephritis; Kidney Glomerulus; Macrophages; Microscopy, Electron; Rabbits

In order to determine the role of intrarenal vascular coagulation (IVC) in chronic glomerulonephritis, coagulant parameters in renal blood (RVB), urine FDP's and renal histology were examined in 70 patients with chronic glomerulonephritis (CGN). RVB was obtained by Seldinger's technique. A correlation was obtained between an increase of fibrinogen, FDP and soluble fibrin monomer complexes (SFMC) in RVB and the degree of intraglomerular fibrin deposition shown on immunofluorescence. An increase of FDP's, SFMC and a slight decrease of fibrinolytic activity in RVB were observed in patients with CGN with decreased renal function or with the nephrotic syndrome. Daily excretion of FDP in the urine and the extent of intraglomerular fibrin deposition were greater in nephrotics than in non-nephrotics. We conclude that measurement of coagulation parameters in RVB is a reliable and sensitive method of assessing IVC, and that IVC plays an important role in aggravation of chronic glomerulonephritis, particularly when the nephrotic syndrome is present.

Topics: Chronic Disease; Fibrin; Fibrin Fibrinogen Degradation Products; Glomerulonephritis; Histocytochemistry; Humans; Kidney Failure, Chronic; Kidney Glomerulus; Nephrotic Syndrome; Renal Veins

Topics: Adolescent; Adult; Female; Fibrin; Glomerulonephritis; Humans; Immunity, Cellular; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male

Topics: Blood Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Glomerulonephritis; Heparin; Humans; Kidney Glomerulus; Plasminogen; Thrombosis; Urokinase-Type Plasminogen Activator

Topics: Chronic Disease; Coronary Disease; Fibrin; Glomerulonephritis; Humans; Hypertension; Pyelonephritis; Solubility

Detailed immunopathologic studies of early or silent renal alterations in systemic lupus erythematosus have been sparse. The renal biopsies of 16 lupus patients with normal renal function, including 8 with hematuria and/or proteinuria of recent onset, and 8 without clinically detectable renal disease were investigated by light, immunofluorescence, and electron microscopy. Immunoglobulins, complement components, and electron-dense deposits were detected in glomeruli of all patients, regardless of morphologic appearance or lack of clinical evidence of renal involvement. Features of membranous glomerulonepritis were observed in 4 patients with substantial proteinuria. In the remaining 12 patients, including 3 with hematuria and 4 with slight proteinuria, either minimal glomerular alterations or features of mesangial proliferative glomerulonephritis were seen. Transformation of the original disease was demonstrated in 3 of 3 patients rebiopsied within 2 years. The significance of these findings is discussed in relation to a) the spectrum of clinical and immunopathologic alterations in lupus nephritis and b) transformation of the original disease.

Topics: Adolescent; Adult; Basement Membrane; Complement System Proteins; Female; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunoglobulins; Kidney; Kidney Glomerulus; Lupus Erythematosus, Systemic; Male; Middle Aged

Correlations between immunofluorescent protein deposits in the glomeruli, urinary sediment and proteinuria selectivity pattern have been attempted in different glomerulonephritis. The overall study showed following results: a) Glomerular and urinary casts deposits of immunoglobulins, C3 and fibrin/fibrinogen are related to moderately selective proteinuria; b) IgG and IgA are most often found in urinary sediment and c) Glomerular deposits of IgG and IgA are well correlated with the presence of these immunoglobulins in urinary casts. Analysis according to different histological types of nephritis: a) In "minimal changes" nephropathy, deposits are infrequent and well correlated with urinary sediment, when they are present; b) In lupus nephritis, constant and intense glomerular deposits of immunoglobulins, fibrin/fibrinogen are correlated with the same proteins found in urinary casts; c) Inconstant correlations are found in membranous nephritis and in IgA-IgG nephropathy.

Topics: Complement C3; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunoelectrophoresis; Immunoglobulins; Kidney Glomerulus; Proteinuria

A model of antiglomerular basement membrane nephritis in the rat was used to elucidate the origin of urinary fibrin-fibrinogen-related antigen (FRA). The intrarenal distribution and excretion of 125I-rat fibrinogen was examined to determine whether there was increased filtration of bibrinogen or fibrin degradation products (FDP) or lysis of intraglomerular fibrin. 125I-protein appeared in the urine immediately after injection of 125I-fibrinogen and fell in parallel with the fall in plasma 125I-fibrinogen. Renal retention of 125I-fibrin averaged less than 0.2 percent of the administered dose of 125I-fibrinogen. The infusion of epsilon aminocaproic acid (EACA) had no significant effect on either FRA excretion or 125I-protein excretion. Plasma FDP levels and the elution patteren of 125I-protein from the urine were not significantly changed by EACA infusion. These observations support the view that ruinary FRA excretion in glomerulonephritis is derived predominantly from increased filtration of plasma fibrinogen rather than from breakdown of intraglomerular fibrin.

Topics: Aminocaproates; Animals; Antibodies; Antigens; Basement Membrane; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Glomerulonephritis; Humans; Infusions, Parenteral; Inulin; Kidney Function Tests; Proteinuria; Rats; Sodium Chloride

The presence of IgA with IgG, C', IgM and fibrin in 365 renal biopsy specimens has been studied by the immunohistological method. Glomerular IgA deposits were found in 38 cases (10.4%). The patients were divided into two groups according to the localization of IgA: 13 cases (3.56%) belonged to the first group, in which IgA showed diffuse mesangial localization. Light microscopic examination showed various stages of proliferative glomerulonephritis. These cases corresponded to the nephropathy described by Berger. In 25 cases (6.85%), belonging to the second group, the glomerular localization of IgA was found to be segmental and peripheral, appeared always in patches and was present with various histological alterations. Differentiation of the two kinds of alteration is possible primarily on the basis of the immunohistological pattern, but light microscopic and electron microscopic examination might also be helpful.

Topics: Biopsy; Fibrin; Glomerulonephritis; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Kidney

Topics: Animals; Disease Models, Animal; Factor VIII; Fibrin; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Immunoglobulin G; Immunoglobulin M; Injections, Intraperitoneal; Kidney Glomerulus; Male; Nephrectomy; Proteinuria; Puromycin Aminonucleoside; Rats; Sialoglycoproteins

Topics: Blood Coagulation; Child; Fibrin; Fibrinogen; Glomerulonephritis; Humans

Topics: Blood Coagulation; Fibrin; Fibrinolysis; Glomerulonephritis; Humans; Infant; Kidney; Kidney Medulla; Kidney Tubules

Topics: Child; Chronic Disease; Fibrin; Fibrinolysis; Glomerulonephritis; Humans; Kidney; Serum Globulins

Topics: Animals; Antibodies; Antibody Formation; Antibody Specificity; Antigen-Antibody Complex; Antilymphocyte Serum; Blood Platelets; Complement System Proteins; Cytotoxicity Tests, Immunologic; Dogs; Fibrin; Glomerulonephritis; Graft Rejection; HLA Antigens; Humans; Immunity; Immunity, Cellular; Kidney; Kidney Transplantation; Mice; Neutrophils; Rats; Time Factors; Transplantation Immunology; Transplantation, Homologous

Immunofluorescent studies were performed on 217 percutaneous renal biopsies on patients with various renal diseases, which were examined in detail to assess the amount, character, and distribution of fibrin deposits in the glomeruli. The fibrin deposits were classified into six different forms on immunohistologic grounds. These were adhesive, adhesive and occlusive, membranous, mesangial, crescent forming, and sclerotic types. The sclerotic type was further subdivided into 2 groups: periglomerular fibrosing, and sclerosis with occlusion types. In many instances, immunofluorescence may reveal a pattern which is commonly associated with a characteristic abnormality on light microscopy. Fibrin deposits were commonly correlated with the presence of glomerular immunoglobulin and betaIc/betaIa-globulin. These findings interpreted as the immune reaction within glomeruli leads to an initiation of the coagulation process. The patrular hyalinization are briefly discussed.

Topics: Adolescent; Adult; Aged; Antigen-Antibody Complex; Female; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Hypertension; Immunity; Immunoglobulins; Kidney Diseases; Kidney Glomerulus; Male; Middle Aged

Newborn Finnish Landrace lambs subsequently affected with mesangiocapillary glomerulonephritis (MCGN) were deficient in the third component of complement (C'3), serum levels being approximately 5 per cent. of those in unaffected lambs. Hypocomplementaemia persisted until symptoms of renal failure occurred at around 6-8 wk of age. Immunofluorescence examinations of renal cortex with antisera specific for IgG, IgM, IgA, C'3 and fibrin supported previous morphological evidence of a strong similarity between this disease and MCGN in man. Similar examinations of choroid plexus suggested that immune complexes containing IgG, IgM and C'3 were present in the interstitium.

Topics: Animals; Choroid Plexus; Colostrum; Complement C3; Complement System Proteins; Fibrin; Glomerulonephritis; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Kidney Cortex; Sheep; Sheep Diseases

Two patients developed acute renal failure; creatinine clearances fell to 13 and 34 ml/min, respectively, and one patient was oliguric. Renal biopsies in both patients gave results that were compatible with rapidly progressive glomerulonephritis (RPGN). Both patients were treated with low-dosage heparin sodium infusion (8,000 units/day) and prednisone for two to four weeks, followed by oral anticoagulant (warfarin) and antithrombotic agents (dipyridamole). In the two patients, creatinine clearance rose to at least 60 ml/min, and no bleeding complications were observed. Repeat renal biopsy specimens that were obtained after three to six months of treatment showed no evidence of active glomerulonephritis in either patient, but there was extensive scarring and fibrosis. Low-dosage heparin infusion may arrest and partially reverse the renal failure associated with RPGN in some cases, while avoiding the bleeding complications that are frequently observed in patients treated with larger dosages of heparin.

Topics: Administration, Oral; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fibrin; Glomerulonephritis; Heparin; Humans; Infusions, Parenteral; Kidney Function Tests; Kidney Glomerulus; Male; Middle Aged; Prednisone; Prothrombin Time; Warfarin

A new procedure, plasma fibrinogen chromatography, has been utilized, together with other blood coagulation assays, to quantify fibrin formation in 43 children with acute poststreptococcal glomerulonephritis (AGN) from the time of hospitalization until recovery. During the prediuretic phase of AGN, significant evidence for substantial increase in fibrin formation (intravascular coagulation) included gross increase in plasma high molecular weight fibrinogen complexes (HMWFC), the development of either hypo- or hyperfibrinogenemia and gross depression of coagulation factor XIII concentration and of alpha2-macroglobulin concentration. During the diuretic phase of the disease, these abnormalities regressed and evidence of enhanced plasma fibrinolytic activity, documented by an increase in fibrinogen first derivative, was detected. Concomitantly, urinary excretion of fibrin(ogen) degradation products (FDP) underwent substantial increase. With disease recovery, which occurred in all children, urinary FDP excretion ceased and all coagulation findings normalized.

Topics: Acute Disease; Adolescent; Blood Coagulation Factors; Blood Coagulation Tests; Child; Child, Preschool; Chromatography, Gel; Disseminated Intravascular Coagulation; Diuresis; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Glomerulonephritis; Humans; Kidney Function Tests; Molecular Weight; Prognosis; Streptococcal Infections

A simple, easily reproducible periodic acid-Schiff-light green stain (PAS-LG) for the detection of glomerular protein deposits by routine light microscopy is described. The deposits are selectively stained a deep blue and contrast sharply with the staining of adjacent glomerular structures. Correlation with immunofluorescent and electron microscopy has shown that it is possible with this stain to categorize accurately a large variety of glomerular lesions by light microscopy alone.

Topics: Antigen-Antibody Complex; Basement Membrane; Cell Nucleolus; Cell Nucleus; Complement System Proteins; Cytoplasm; Erythrocytes; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunoglobulin A; Immunoglobulin G; Indicators and Reagents; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Microscopy, Electron; Periodic Acid; Proteins; Staining and Labeling

To elucidate the origin of the fibrin/fibrinogen degradation products (F.D.P.) occurring in the urine in glomerulonephritis 28 patients with glomerulonephritis were examined for renal fibrinolytic activity, F.D.P. in urine and serum, and blood fibrinolytic activators and blood fibrinolytic activators and inhibitors. Unlike the glomerful of healthy kidneys, which were fibrinolyticly inactive, those of kidneys with glomerulonephritis constantly showed fibrinolytic activity. The presence or absence of fibrin in the glomeruli was almost always accompanied by, respectively, the presence or absence of urinary F.D.P., which suggested a renal origin of urinary F.D.P. in glomerulonephritis. The low fibrinolytic activity of the blood and the absence of F.D.P. in the serum of these patients make it unlikely that the urinary F.D.P. in glomerulonephritis result from glomerular filtration.

Topics: Alpha-Globulins; Fibrin; Fibrinogen; Fibrinolysis; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Kidney Cortex; Kidney Glomerulus; Macroglobulins; Urokinase-Type Plasminogen Activator

On healthy individuals fibrin(ogen) split products cannot be demonstrated in the blood. Catabolic products of fibrin and fibrinogen appear in the blood in case of general fibrinolysis, consumption coagulopathy with secondary fibrinolysis as well as local fibrin films with secondary fibrinolysis. The regular routine determination of fibrin(ogen) split products in serum or urine may indicate starting complications of many diseases. The appearance of these split products in case of renal affections indicates acute and active processes on the kidneys themselves; fibrin films appear in case of acute and chronic glomerulonephritis, casting-off crises on renal transplants, EPH gestosis, renal phlebothrombosis, hemolytic-uremic syndrom and occasionally urinary tract infections. The demonstration of fibrin(ogen) split products in serum or urine allows the following conclusions: a) acute and active process on the kidneys themselves; b) HMWS in urine indicate a fibrin film in the kidneys; c) an immediate beginning of an anticoagulation therapy; d) good possibilities to judge the therapeutic effect and by this the further progress of disease.

Topics: Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Graft vs Host Reaction; Hemolytic-Uremic Syndrome; Humans; Immunoelectrophoresis; Infant; Kidney Diseases; Kidney Transplantation; Molecular Weight; Pre-Eclampsia; Pregnancy; Prognosis; Thrombosis; Transplantation, Homologous; Urinary Tract Infections

The urinary concentration of fibrin-fibrinogen degradation products (F.D.P.) was measured in 90 patients with proteinuria above 2 g/1 and correlated with proteinuria, differential protein clearances, serum urea and creatinine, and renal biopsy findings. There was a linear correlation (r equals 0-7; P less than 0-001) between the urinary F.D.P. excretion and the selectivity of the proteinuria such that patients with highly selective proteinuria excreted only small amounts of F.D.P. whereas those with non-selective proteinuria excreted much higher levels. There was a significant correlation between the urinary F.D.P. excretion and the urine:serum (U:S) ratio of IgG excretion but not with the U:S ratio or urinary excretion of albumin or transferrin. Sephadex G200 column chromatography of the concentrated urine in 26 cases showed that patients with highly selective proteinuria excreted predominantly F.D.P. of low molecular weight in the urine whereas those with non-selective proteinuria excreted mainly fibrinogen and products of high molecular weight. Hence the type and quantity of F.D.P. in the urine are determined primarily by the differential filtration of fibrinogen and the various degradation products from the plasma through the glomerular basement membrane, which in turn is determined by the "pore size" of the basement membrane. In clinical nephrology measurement of the urinary F.D.P. level provides a rapid and convenient means of estimating the differential protein clearance.

Topics: Albuminuria; Amyloidosis; Chromatography; Fibrin; Fibrinogen; Filtration; Glomerular Filtration Rate; Glomerulonephritis; Humans; Hypersensitivity; Hypertension, Malignant; Immunodiffusion; Immunoglobulin G; Lupus Erythematosus, Systemic; Molecular Weight; Nephrotic Syndrome; Proteinuria; Purpura; Thrombosis; Transferrin

Topics: Arteritis; Biopsy; Child; Complement System Proteins; Diagnosis, Differential; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunoglobulin G; Kidney; Kidney Glomerulus; Male; Microscopy, Electron; Streptococcal Infections

During experimental Masugi nephritis in the rabbit, were demonstrated various disturbances in hemostasis: a) during the initial stage: immediate, severe and transient fall in the platelet count without any change in Factor V;b)during the secondary stage, from the 7th to the 8th day onwards, increase in platelets and fibrinogen, in relation with the intensity of the nephrotic syndrome; c) in parallel, appearance of urinary fibrinogen split products in relation to the intensity of the glomerular lesions, evidence for the presence of intraglomerular fibrin. These facts confirm the role played by platelets in coagulation phenomena secondary to the immune reaction. They indicate, furthermore, the existence of hemostasis disorders during the nephrotic syndrome.

Topics: Animals; Antigens; Blood Cell Count; Blood Coagulation; Blood Platelets; Complement System Proteins; Ducks; Factor V; Fibrin; Fibrinogen; Glomerulonephritis; Hematocrit; Immune Sera; Kidney Glomerulus; Nephrotic Syndrome; Platelet Aggregation; Proteinuria; Rabbits

The concentration of fibrin/fibrinogen degradation products in urine (FDPu) was measured in samples obtained from 114 patients and 63 clinically healthy volunteers, once or repeatedly. The FDP titers measured by the hemagglutination inhibition (HI) method corresponded to less than 2.6 mug/ml FDP in all samples from healthy controls. Slightly elevated FDP concentrations were found in urine obtained from a few patients with disorders not primarily involving the urinary tract. The clinical importance of these isolated findings remains unclear. Urinary tract infections were not frequently accompanied by elevated FDPu concentrations. In patients with glomerulonephritis FDP excretion correlated somewhat better with severity of the renal affection. A further group of patients showed an unequivocal correlation between FDP excretion in the urine and postoperative complications following renal transplantation. However, the clinical diagnosis of acute rejection crisis was usually established at the same time or even before an increase in FDPu was found. Our results suggest that among diagnostic procedures the measurement of FDPu contributes little specific information for the evaluation of urinary tract disease. FDPu measurements in the immediate postoperative phase following renal transplantation may however be important for prognostic evaluation and, in individual cases, predict transplant rejection. We also attempted to define the FDPu qualitatively by simultaneous measurements using HI and the staphylococcal clumping test (SCT). Immunoelectrophoresis confirmed the well-known fact that the SCT detects only high-molecular FDP; this limits its clinical usefulness, despite its high sensitivity.

Topics: Female; Fibrin; Fibrinogen; Glomerulonephritis; Graft Rejection; Hemagglutination Inhibition Tests; Humans; Hydronephrosis; Kidney Calculi; Kidney Transplantation; Male; Pregnancy; Pregnancy Complications; Proteinuria; Pyelonephritis; Time Factors; Transplantation, Homologous; Urologic Diseases

Topics: Fibrin; Glomerulonephritis; Humans

Topics: Adolescent; Adult; Aged; Child; Female; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Humans; Male; Middle Aged; Nephrotic Syndrome

Topics: Adolescent; Child; Child, Preschool; Fibrin; Fibrinogen; Glomerulonephritis; Histocytochemistry; Humans; Kidney Glomerulus

The effect of heparin on the development and progression of a form of antiglomerular basement membrane nephritis was examined in the rat. Animals which received heparin before and throughout the period of immunological insult developed lesions which were as severe, and perhaps more severe, than rats which did not receive heparin. Inulin clearances were lower in heparin-treated animals than in untreated rats. Animals in both groups exhibited renal fibrin-fibrinogen deposition and had increased rates of urinary fibrin-fibrinogen related antigen excretion. These results indicate that heparin per se has no beneficial effect on the development of this form of glomerulonephritis in this species.

Topics: Animals; Basement Membrane; Fibrin; Fibrinogen; Glomerulonephritis; Goats; Heparin; Kidney; Kidney Glomerulus; Rabbits; Rats

Topics: Blood Coagulation; Child; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Humans; Kidney; Nephritis

Topics: Adolescent; Child; Child, Preschool; Fibrin; Fibrinogen; Glomerulonephritis; Humans; Kidney Glomerulus

Topics: Adolescent; Animals; Child; Child, Preschool; Female; Fibrin; Glomerulonephritis; Humans; Kidney Glomerulus; Male; Rabbits

Topics: Adult; Animals; Blood Urea Nitrogen; Creatinine; Disseminated Intravascular Coagulation; Female; Fibrin; Glomerulonephritis; Humans; Hyalin; Kidney; Kidney Glomerulus; Lung; Male; Middle Aged; Pneumococcal Infections; Pneumonia, Pneumococcal; Proteinuria; Rats; Sepsis; Streptococcus pneumoniae; Thrombosis; Uremia

Topics: Amyloid; Arthritis, Rheumatoid; Basement Membrane; Biopsy; Blood Proteins; Complement System Proteins; Diagnosis, Differential; Fibrin; Glomerulonephritis; Glycoproteins; Granulomatosis with Polyangiitis; Histocytochemistry; Humans; Hypersensitivity; Immunoglobulins; Kidney Glomerulus; Methenamine; Methods; Proteins; Purpura; Silver; Staining and Labeling

Using a radial immunodiffusion technique we measured the urinary concentration of material related to complement (C3), IgM, and IgG along with fibrin-fibrinogen degradation products and heterophile (sheep) haemagglutinins in 15 patients with proliferative glomerulonephritis and in 10 patients after renal transplantation. There was a significant correlation between all variables measured, and serial studies showed that with the exception of IgG-related materials potentially useful information could be obtained on the detection of rejection and the response to treatment in both conditions. The significance of these observations is discussed.

Topics: Animals; Antibodies, Heterophile; Biodegradation, Environmental; Complement System Proteins; Female; Fibrin; Fibrinogen; Glomerulonephritis; Hemagglutination Inhibition Tests; Humans; Immunodiffusion; Immunoglobulin Fragments; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Indomethacin; Kidney Transplantation; Male; Sheep; Transplantation, Homologous; Urea

Topics: Antigens; Blood Coagulation; Chromatography; Chromatography, Gel; Fibrin; Fibrinogen; Glomerulonephritis; Hemagglutination Inhibition Tests; Humans; Immunodiffusion; Iodine Radioisotopes; Kidney Transplantation; Methods; Time Factors; Transplantation, Homologous

Topics: Acute Kidney Injury; Biopsy; Cell Migration Inhibition; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immune Complex Diseases; Male; Necrosis; Peritoneal Dialysis; Proteinuria; Remission, Spontaneous; Streptococcal Infections

Light, immunofluorescence and electron microscopic studies were carried out on renal biopsies from 32 randomly selected adult monkeys (Macaca irus). Histopathology was limited to glomeruli and consisted of mild to moderate segmental increases in mesangial cells, mesangial matrix, and/or glomerular basement membrane (GBM) thickness in 41% of the animals. Granular deposits of IgM were present in the mesangial region and along the GBM in 72% of the monkeys, whereas IgG, C1q, C4 and C3 were detected in approximately 30%. Electrondense deposits were seen predominantly in epithelial foot processes adjacent to the GBM and, to a lesser extent, in the mesangium. Those monkeys with the heaviest IgM deposition were found to have decreased serum levels of C3, IgM and IgA. Follow-up biopsies over a period of 3 to 11 months revealed that the disease process was persistent yet nonprogressive. No correlation with age or sex was noted. All animals examined were clinically healthy and had normal renal function. This is the first documented occurrence of spontaneous immune-complex glomerulonephritis in a large monkey population. It appears to be a persistent disease which does not progress to renal insufficiency and which may serve as an investigative model for mild nonprogressive forms of human glomerulonephritis.

Topics: Animals; Biopsy; Complement System Proteins; Disease Models, Animal; Female; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Haplorhini; Immune Complex Diseases; Immune Sera; Immunodiffusion; Immunoglobulin G; Immunoglobulin M; Kidney; Kidney Glomerulus; Macaca; Male; Microscopy, Electron

Topics: Acute Kidney Injury; Anemia; Basement Membrane; Blood Coagulation Disorders; Capillaries; Epithelial Cells; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Hematuria; Histocytochemistry; Humans; Immunoglobulins; Kidney; Kidney Glomerulus; Kidney Tubules; Microscopy, Electron; Prognosis; Proteinuria; Statistics as Topic

C3 and fibrin degradation products (F.D.P.) have been measured in early morning urine samples from 38 normal people and 123 patients with glomerulonephritis. Normal urine contained less than 0.3 mug of either antigen per ml. C3 and F.D.P. were both detected in the urine of many patients with glomerulonephritis. Levels above 1 mug/ml were exceptional in patients with "minimal change," and the highest excretion of both antigens occurred in mesangiocapillary glomerulonephritis, membranous nephropathy, and focal glomerulosclerosis.Both C3 and F.D.P. excretion showed considerable variation with time, with parellel fluctuations in the two antigens. These fluctuations did not depend on the total protein leakage and suggest that the complement and clotting sequence are closely related in these glomerular disorders.

Topics: Antigens; Blood Coagulation; Circadian Rhythm; Complement System Proteins; Fibrin; Glomerulonephritis; Hemagglutination Inhibition Tests; Humans; Kidney Diseases; Kidney Glomerulus; Time Factors

Topics: Adult; Anti-Glomerular Basement Membrane Disease; Blood Coagulation Disorders; Female; Ferritins; Fibrin; Glomerulonephritis; Hemorrhagic Disorders; Humans

The relations between glomerular fibrin deposition, urinary excretion of fibrinogen derivatives (F.D.), and proteinuria were explored in 81 patients with glomerulonephritis. A positive correlation existed between proteinuria and F.D. excretion even when no fibrin could be detected in the glomerulus. In two patients with tubular proteinuria F.D. excretion was also raised, suggesting that tubular reabsorption or catabolism of F.D. or both normally occur.Disproportionately high titres of F.D. were observed when fibrin was deposited in an extracapillary site, but mesangial fibrin deposition was not accompanied by a higher excretion of F.D. than that observed in patients in whom intraglomerular fibrin was not detected. These observations suggest that the immunofluorescent findings on renal biopsies should be the major criteria on which a trial of anticoagulants in proliferative glomerulonephritis might be instituted and that measurement of urinary F.D. is likely to be of value in monitoring therapy in patients with extracapillary fibrin deposition.

Topics: Biopsy; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Hemagglutination Inhibition Tests; Humans; Kidney Glomerulus; Proteinuria

Topics: Adult; Autopsy; Biopsy; Complement System Proteins; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Kidney; Kidney Diseases; Kidney Glomerulus; Lupus Erythematosus, Systemic; Microscopy, Electron; Nephritis; Prognosis; Time Factors

Topics: Aspirin; Blood Coagulation; Complement System Proteins; Diabetic Nephropathies; Dipyridamole; Fibrin; Fibrinogen; Glomerulonephritis; Hemolytic-Uremic Syndrome; Heparin; Humans; Iodine Radioisotopes; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Plasminogen; Proteinuria; Thrombosis; Transplantation, Homologous; Uremia; Warfarin

Indomethacin given to adults with glomerulonephritis usually reduces their urinary excretion of protein and fibrinogen/fibrin-related (F.R.) antigen. Nevertheless, non-responders exist. Platelet aggregation is significantly more strongly inhibited by indomethacin in good responders than in nonresponders. This supports the hypothesis that the reduction of urinary excretion of F.R. antigen during indomethacin administration is related, at least in part, to inhibition of intrarenal platelet aggregation and of the subsequent fibrin deposition.

Topics: Adolescent; Adult; Antigens; Blood Coagulation; Blood Platelets; Chronic Disease; Creatinine; Female; Fibrin; Glomerulonephritis; Humans; Indomethacin; Male; Middle Aged; Platelet Adhesiveness; Proteinuria

Topics: Acute Disease; Adolescent; Adult; Animals; Antibodies, Heterophile; Antibody Specificity; Female; Fibrin; Fibrinogen; Glomerulonephritis; Graft Rejection; Hemagglutination; Humans; Indomethacin; Kidney Transplantation; Male; Middle Aged; Sheep; Transplantation, Homologous

Topics: Adolescent; Adult; Anti-Glomerular Basement Membrane Disease; Autopsy; Basement Membrane; Collagen; Endocarditis, Subacute Bacterial; Epithelial Cells; Epithelium; Female; Fibrin; Glomerulonephritis; Humans; Kidney Glomerulus; Leukocytes; Male; Middle Aged; Polyarteritis Nodosa; Staining and Labeling

Topics: Adolescent; Adult; Animals; Antibodies; Child; Chromatography, Gel; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrinogen; Fibrinolysis; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Hydrocortisone; Immunodiffusion; Immunoelectrophoresis; Middle Aged; Nephrosis, Lipoid; Proteinuria; Rabbits

Topics: Adult; Anti-Glomerular Basement Membrane Disease; Antibodies, Viral; Antibody Formation; Antibody Specificity; Complement Fixation Tests; Complement System Proteins; Female; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Hemagglutination Inhibition Tests; Herpesvirus 4, Human; Humans; Immunodiffusion; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Lupus Erythematosus, Systemic; Male; Measles virus; Nephrosis, Lipoid; Orthomyxoviridae; Respirovirus; Rubella virus; Serum Albumin

In 40 patients with a histological diagnosis of proliferative glomerulonephritis the deposition of immunoglobulins, complement (C(3)), and fibrin/fibrinogen has been assessed by immunofluorescence and electron microscopy. The results of such examinations have been correlated with the outcome of the illness. In minor or resolving disease there is usually minor functional impairment, a good response to therapy or spontaneous resolution, the deposition of small amounts of material in glomerular capillary walls, and active mesangial removal. In moderate to marked disease there is initially a moderately severe functional disorder, a good response to therapy, considerable deposition of material in glomerular capillary walls but with less active mesangial regions than in the previous group. In progressive glomerulonephritis there was initial severe functional disorder, poor response to therapy, large amounts of material deposited within capillary walls, and active mesangial regions which were greatly enlarged, containing numerous deposits. In the rapidly progressive group there was severe functional disorder with poor response to therapy, the deposition of only small amounts of material within capillary walls, the lack of any significant mesangial cell reaction, and the formation of epithelial crescents. The results of the study indicate that in proliferative glomerulonephritis following the deposition of material in glomerular capillary loops, the progression of the disease is, to some extent at least, dependent upon the ability of the mesangial cell to remove such material.

Topics: Adolescent; Adult; Aged; Capillaries; Child; Child, Preschool; Complement System Proteins; Epithelium; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunoglobulins; Kidney Function Tests; Kidney Glomerulus; Male; Microscopy, Electron; Middle Aged

Topics: Biopsy; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Histocytochemistry; Humans; Kidney; Kidney Function Tests; Microscopy, Electron; Prognosis

Topics: Albuminuria; Animals; Chromatography, Gel; Chromatography, Ion Exchange; Fibrin; Fibrinogen; Glomerular Filtration Rate; Glomerulonephritis; Humans; Immunoelectrophoresis; Kidney Transplantation; Molecular Weight; Muramidase; Nephrosis; Plasminogen; Rabbits; Streptokinase; Transplantation, Homologous; Uremia

Topics: Complement System Proteins; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Microscopy, Electron

Topics: Adult; Basement Membrane; Biopsy, Needle; Complement System Proteins; Female; Fibrin; Fluorescent Antibody Technique; Follow-Up Studies; Glomerulonephritis; Histocytochemistry; Humans; Hyperplasia; Immunoglobulin G; Immunosuppression Therapy; Kidney Glomerulus; Male; Microscopy, Electron

Topics: Acute Kidney Injury; Adult; Anticoagulants; Azathioprine; Biopsy; Cyclophosphamide; Dipyridamole; Female; Fibrin; Fluorescent Antibody Technique; Glomerular Filtration Rate; Glomerulonephritis; Heparin; Humans; Kidney Glomerulus; Male; Middle Aged; Prednisolone; Snake Venoms; Time Factors; Warfarin

Topics: Agglutinins; Animals; Antibodies, Heterophile; Complement System Proteins; Fibrin; Fibrinogen; Glomerulonephritis; Graft Rejection; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Indomethacin; Kidney Transplantation; Sheep; Transplantation, Homologous

Topics: Adolescent; Adult; Animals; Antibody Specificity; Biopsy; Child; Complement System Proteins; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Hemagglutination Tests; Humans; Immune Sera; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulin G; Kidney; Male; Microscopy, Electron; Middle Aged; Phagocytosis; Rabbits

Topics: Fibrin; Glomerulonephritis; Hemolytic-Uremic Syndrome; Kidney Diseases; Nephrosis; Purpura; Urinary Tract Infections

Topics: Adolescent; Adult; Aged; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Complement System Proteins; Creatinine; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Humans; Kidney Diseases; Kidney Glomerulus; Lupus Erythematosus, Systemic; Male; Middle Aged; Proteinuria; Prothrombin Time

Topics: Adolescent; Child; Child, Preschool; Female; Fibrin; Glomerulonephritis; Hematuria; Humans; Hypersensitivity; Immunoglobulin A; Immunoglobulin G; Immunosuppression Therapy; Male; Proteinuria; Purpura; Respiratory Tract Infections; Serum Globulins

Topics: Adult; Basement Membrane; Biopsy; Child; Complement System Proteins; Diagnosis, Differential; Female; Fibrin; Focal Infection; Glomerulonephritis; Hematuria; Humans; Immunoglobulins; Kidney; Kidney Glomerulus; Male; Microscopy, Electron

Topics: Animals; Antibodies, Heterophile; Biopsy; Fibrin; Glomerulonephritis; Immune Sera; Kidney; Proteinuria; Rabbits

Topics: Adolescent; Adult; Blood Coagulation; Complement System Proteins; Female; Fibrin; Glomerulonephritis; Humans; Male; Middle Aged

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Azathioprine; Child; Child, Preschool; Epithelial Cells; Epithelium; Female; Fibrin; Glomerulonephritis; Glucocorticoids; Heparin; Humans; Hyperplasia; Infant; Infant, Newborn; Kidney Glomerulus; Male; Middle Aged; Renal Dialysis

Topics: Anti-Glomerular Basement Membrane Disease; Autopsy; Basement Membrane; Biopsy; Capillaries; Endoplasmic Reticulum; Epithelial Cells; Epithelium; Fibrin; Glomerulonephritis; Humans; Kidney Glomerulus; Kidney Tubules; Microscopy, Electron; Thrombosis

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Anticoagulants; Australia; Azathioprine; Biopsy; Creatinine; Cyclophosphamide; Dipyridamole; Female; Fibrin; Glomerulonephritis; Heparin; Humans; Kidney; Kidney Glomerulus; Male; Middle Aged; Prednisolone; Prognosis; Renal Dialysis; Seasons; Steroids; Warfarin

Topics: Adolescent; Aged; Anticoagulants; Biopsy; Child; Drug Therapy, Combination; Epithelial Cells; Epithelium; Female; Fibrin; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney Glomerulus; Male

Topics: Adolescent; Adult; Aged; Antigens; Child; Chromatography, Gel; Creatinine; Female; Fibrin; Fibrinogen; Follow-Up Studies; Glomerulonephritis; Humans; Indomethacin; Kidney; Kidney Function Tests; Male; Middle Aged; Proteinuria

Topics: Abortion, Induced; Adolescent; Biopsy; Female; Fibrin; Glomerulonephritis; Humans; Kidney; Kidney Function Tests; Lupus Erythematosus, Systemic; Pregnancy; Pregnancy Complications; Prognosis; Proteinuria

Topics: Adenosine Diphosphate; Adult; Animals; Blood Cell Count; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Erythrocytes; Female; Fibrin; Fibrinogen; Glomerulonephritis; Hemagglutination Inhibition Tests; Humans; Immunoglobulin A; Immunoglobulin G; Kidney Glomerulus; Male; Middle Aged; Nephritis; Platelet Aggregation; Polymers; Renal Veins; Sheep; Thrombin

Topics: Acute Kidney Injury; Basement Membrane; Blood Coagulation Disorders; Diabetic Nephropathies; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Hemagglutination Tests; Hemolytic-Uremic Syndrome; Humans; Ischemia; Kidney; Kidney Diseases; Male; Middle Aged; Pre-Eclampsia; Pregnancy; Thrombosis; Urokinase-Type Plasminogen Activator

Topics: Female; Fibrin; Glomerulonephritis; Humans; Pre-Eclampsia; Pregnancy; Proteinuria

Topics: Acute Disease; Blood Coagulation Disorders; Blood Urea Nitrogen; Factor VIII; Fibrin; Fibrinolysin; Fibrinolysis; Glomerulonephritis; Humans; Thromboplastin; Time Factors

Topics: Animals; Antibodies; Basement Membrane; Biopsy; Cell Nucleus; Cytoplasmic Granules; Ducks; Endothelium; Epithelial Cells; Fibrin; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Goats; Immune Sera; Immunoglobulin G; Kidney Glomerulus; Leukocytes; Microscopy, Electron; Monocytes; Rabbits

Topics: Adult; Disseminated Intravascular Coagulation; Fibrin; Fibrinolysis; Glomerulonephritis; Humans; Kidney Glomerulus; Middle Aged; Polyarteritis Nodosa; Prothrombin Time

Topics: Acute Kidney Injury; Erythrocytes; Fibrin; Glomerulonephritis; Graft Rejection; Hemagglutination Inhibition Tests; Humans; Kidney Diseases; Kidney Transplantation; Pyelonephritis; Transplantation, Homologous; Ureteral Obstruction

Topics: Adolescent; Child; Child, Preschool; Complement System Proteins; Female; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Male; Streptococcal Infections

Topics: Acute Kidney Injury; Animals; Antigens; Fibrin; Fibrinogen; Glomerulonephritis; Humans; Kidney Diseases

Topics: Adenosine Diphosphate; Aspirin; Blood Coagulation; Blood Coagulation Factors; Blood Platelets; Fibrin; Freezing; Glomerulonephritis; Heparin Antagonists; Humans; Indomethacin; Microcirculation; Serotonin

Topics: Acute Kidney Injury; Disseminated Intravascular Coagulation; Female; Fibrin; Glomerulonephritis; Heparin; Kidney Diseases; Nephritis, Interstitial; Pregnancy; Pregnancy Complications, Infectious; Sepsis

Topics: Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Glomerular Filtration Rate; Glomerulonephritis; Heparin; Humans

Topics: Acute Disease; Child; Fibrin; Fibrinolysis; Glomerulonephritis; Hemostasis; Humans; Kidney Diseases; Pyelonephritis

The concentration of serum fibrinogen-fibrin-related antigen (F.R.-antigen) was measured in a group of 142 patients with various renal disorders, in 38 of whom urine F.R.-antigen was also estimated. Raised serum F.R.-antigen levels were present in 48% of the patients, with no particular preponderance in any diagnostic category apart from acute reversible intrinsic renal failure in which high levels were invariably present. Significantly-raised serum levels were also present in the patients with microangiopathic haemolytic anaemia and in those with the more severe degrees of renal impairment. Urine F.R.-antigen was increased in 34 of the 38 patients. The amount of F.R.-antigen in the urine correlated with the degree of proteinuria but not with the serum F.R.-antigen levels. The evidence relating to intravascular coagulation in renal disease is reviewed, and it is suggested that there is a high incidence of localized fibrinogen or fibrin degradation in the kidney, which is related more to factors such as the presence of uraemia and microangiopathic haemolytic anaemia rather than to the diagnostic category.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Anemia, Hemolytic; Antigens; Child; Child, Preschool; Female; Fibrin; Fibrinogen; Glomerulonephritis; Hemagglutination Inhibition Tests; Humans; Hypertension, Malignant; Kidney Diseases; Male; Middle Aged; Proteinuria; Uremia

Topics: Adolescent; Azathioprine; Biopsy; Child; Child, Preschool; Female; Fibrin; Glomerulonephritis; Humans; Immunoglobulin G; Infant; Kidney Glomerulus; Male; Microscopy, Fluorescence; Nephrotic Syndrome; Prednisone; Proteinuria; Purpura; Skin; Syndrome

Topics: Animals; Antigen-Antibody Complex; Beta-Globulins; Blood Platelets; Complement System Proteins; Female; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Histocompatibility; Immunogenetics; Immunoglobulins; Inbreeding; Kidney; Kidney Glomerulus; Kidney Transplantation; Male; Microscopy, Electron; Microscopy, Fluorescence; Rats; Thrombosis; Transplantation Immunology; Transplantation, Homologous

Topics: Adolescent; Adult; Aged; Anticoagulants; Biopsy; Blood Coagulation; Capillaries; Child; Chronic Disease; Female; Fibrin; Fibrinolytic Agents; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney Glomerulus; Male; Microscopy, Electron; Middle Aged

Topics: Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Microscopy, Electron

Topics: Adult; Age Factors; Antibodies; Antigen-Antibody Reactions; Autopsy; Basement Membrane; Biopsy; Complement System Proteins; Female; Fibrin; Glomerular Filtration Rate; Glomerulonephritis; Humans; Immunoelectrophoresis; Immunoglobulin G; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Transplantation; Male; Middle Aged; Neutrophils; Streptococcal Infections; Transplantation, Homologous

Topics: Acute Disease; Blood Coagulation Factors; Blood Urea Nitrogen; Child; Creatinine; Female; Fibrin; Fibrinolysis; Glomerulonephritis; Heparin; Humans; Penicillin V; Prednisolone; Streptococcal Infections; Uremia

Topics: Antigens; Fibrin; Fibrinogen; Glomerulonephritis; Hemagglutination Inhibition Tests; Humans; Immunodiffusion

It appears that in human renal isografts glomerulonephritis in the transplant may be a recurrence of the original disease. In the allograft, nephritis may be either recurrence, an intrinsic part of the rejection process itself, or acquisition de novo of the disease. A number of parallels to both antiglomerular basement membrane disease and circulating antigen-antibody complex disease in the animal model are suggested, but with the possible exception of an occasional demonstration of anti-GBM disease, proof that such mechanisms operate in the glomerulonephritis developing in the human allograft is at present lacking.

Topics: Acute Disease; Adrenal Cortex Hormones; Antigen-Antibody Complex; Antigens, Bacterial; Antilymphocyte Serum; Autoantibodies; Basement Membrane; Chronic Disease; Disease Models, Animal; Fibrin; Glomerulonephritis; Graft Rejection; Humans; Kidney; Kidney Glomerulus; Kidney Transplantation; Recurrence; Streptococcus; Transplantation, Homologous; Transplantation, Isogeneic; Virus Diseases

Topics: Fibrin; Fibrinogen; Glomerulonephritis; Humans; Nephrotic Syndrome

Topics: Fibrin; Fibrinogen; Glomerular Filtration Rate; Glomerulonephritis; Humans

Topics: Adult; Blood Coagulation Tests; Blood Urea Nitrogen; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Glomerulonephritis; Hematologic Diseases; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Nephritis; Nephrotic Syndrome; Urinary Tract Infections; Vascular Diseases

The serum and urine concentrations of fibrin/fibrinogen degradation products (F.D.P.) were estimated in 172 patients with glomerulonephritis. In each case the diagnosis was established on the basis of clinical, renal histological, and ultrastructural findings. Serum F.D.P. concentrations were often raised in all types of glomerulonephritis, though more consistently in active proliferative forms. The urinary concentration provided a reliable and sensitive index of activity, progression, and natural history in proliferative glomerulonephritis. In these forms the urinary F.D.P. content was thought to reflect predominantly lysis of intraglomerular fibrin deposits. In minimal lesion and membranous glomerulonephritis low but abnormal concentrations of urinary F.D.P. were consistently found. It is suggested that in these cases the products are derived from limited proteolysis of fibrinogen filtered through an abnormally permeable basement membrane.Daily measurement of urinary F.D.P. concentration is of potential value in the differential diagnosis of patients with glomerulonephritis and at the same time provides a sensitive assessment of the activity and natural history of proliferative disease.

Topics: Basement Membrane; Biopsy; Creatinine; Diagnosis, Differential; Fibrin; Fibrinogen; Fibrinolytic Agents; Glomerulonephritis; Hemagglutination Tests; Humans; Kidney; Microscopy, Electron; Proteinuria

Topics: Adolescent; Adult; Anemia, Hemolytic; Blood Coagulation Disorders; Blood Pressure; Child, Preschool; Desoxycorticosterone; Erythrocytes; Female; Fibrin; Glomerulonephritis; Humans; Hypertension, Malignant; Kidney Diseases; Male; Middle Aged; Necrosis; Nephrectomy; Urea; Vascular Diseases

Topics: Aleutian Mink Disease; Animals; Antibody Formation; Antigen-Antibody Complex; Complement System Proteins; Fibrin; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Immunoelectrophoresis; Kidney; Kidney Glomerulus; Mink; Rabbits; Serum Albumin

We have investigated the formation of fibrin, platelet aggregates, and subendothelial deposits in lipoid nephrosis. Fibrin formation was found in 10 cases of active lipoid nephrosis. Platelet aggregates were found in eight cases and subendothelial deposits in nine. Fibrin and platelets were also found in cases of nephrotic syndrome due to other causes, and in glomerulonephritis. Fibrin was generally absent in lipoid nephrosis in remission and in benign recurrent hematuria. It is suggested that what seems to be a lower incidence in females is more apparent than real and that fibrin or related material may be present in a less easily identifiable form. Steroid therapy apparently had no effect on the presence or absence of fibrin. Most instances were associated with elevated serum cholesterol and alpha(2)-globulin. It is suggested that elevated serum lipids as well as the disease process in the kidney play a role in this phenomenon. It is further suggested that intraglomerular fibrin formation could lead to irreversible renal damage in lipoid nephrosis.

Topics: Adolescent; Adult; Aged; Alpha-Globulins; Biopsy; Blood Platelets; Child; Child, Preschool; Cholesterol; Chronic Disease; Female; Fibrin; Glomerulonephritis; Hematuria; Histocytochemistry; Humans; Kidney Glomerulus; Male; Microscopy, Electron; Middle Aged; Nephrosis, Lipoid; Nephrotic Syndrome; Sex Factors; Steroids

Topics: Antibody Formation; Antigen-Antibody Reactions; Basement Membrane; Biopsy; Fibrin; Fibrinogen; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Histocompatibility; Histocompatibility Testing; Humans; Immunoglobulin G; Immunoglobulin M; Kidney Glomerulus; Kidney Transplantation; Time Factors; Transplantation Immunology; Transplantation, Homologous

Topics: Aleutian Mink Disease; Animals; Basement Membrane; Capillaries; Cell Division; Cell Membrane; Cytoplasm; Epithelium; Erythrocytes; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Golgi Apparatus; Kidney Glomerulus; Leukocytes; Lysosomes; Microscopy, Electron; Mink; Mitochondria; Neutrophils; Phagocytosis

Topics: Animals; Antigens; Basement Membrane; Complement System Proteins; Fibrin; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Humans; Immune Sera; Immunoglobulin G; Immunoglobulin M; Kidney Glomerulus; Malaria; Plasmodium malariae; Rabbits

Topics: Animals; Basement Membrane; Complement System Proteins; Fibrin; Fibrinogen; Fibrinolytic Agents; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Heparin; Immune Sera; Kidney; Kidney Glomerulus; Mice; Nephritis; Proteinuria; Rabbits

Topics: Agglutination; Amyloidosis; Antigen-Antibody Reactions; Arthus Reaction; Chemical Precipitation; Fibrin; Glomerulonephritis; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Lysogeny; Microscopy, Electron

Topics: Animals; Blood Coagulation; Fibrin; Fibrinogen; Fibrinolysis; Fluorescent Antibody Technique; Glomerulonephritis; Kidney; Mice; Phenols; Proteinuria; Streptococcus; Sulfonic Acids

Topics: Acute Kidney Injury; Cholelithiasis; Cholestasis; Diabetic Nephropathies; Factor XIII; Fibrin; Fibrinogen; Glomerulonephritis; Humans; Kidney Failure, Chronic; Nephrotic Syndrome; Pyelonephritis; Renal Dialysis; Tuberculosis, Renal; Uremia; Wound Healing

Topics: Acute Disease; Animals; Benzenesulfonates; Blood Proteins; Dicumarol; Endopeptidases; Fibrin; Fibrinolytic Agents; Glomerulonephritis; Heparin; Histocytochemistry; Mice; Polymers; Solubility; Streptococcus; Time Factors

Topics: Animals; Antigen-Antibody Reactions; Blood Coagulation; Electrons; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Microscopy; Microscopy, Electron; Pathology; Proteinuria; Rabbits; Research; Warfarin

Topics: Animals; Blood Coagulation; Electrons; Fibrin; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Immune Sera; Kidney Glomerulus; Microscopy; Microscopy, Electron; Nephritis; Pathology; Phagocytosis; Rabbits; Research; Sheep; Toxicology; Warfarin

Topics: Adenosine Triphosphatases; Blood Platelets; Colitis; Colitis, Ulcerative; Dihydrolipoamide Dehydrogenase; Endocarditis; Fibrin; Geriatrics; Glomerulonephritis; Histocytochemistry; Humans; Mitral Valve; Pathology; Polysaccharides; Rheumatic Heart Disease; Thrombosis

Topics: Animals; Electrons; Female; Fibrin; Glomerulonephritis; Humans; Kidney Diseases; Kidney Glomerulus; Microscopy; Microscopy, Electron; Pathology; Phagocytosis; Pre-Eclampsia; Pregnancy; Rabbits; Research; Sepsis; Thromboplastin