fibrin and Kidney-Diseases

Fibrinogen is a unique protein that is converted into an insoluble fibrin in a single enzymatic event, which is a characteristic feature of fibrinogen due to its susceptibility to fibrinolytic degradation and dissolution. Although thrombosis is a result of activated blood coagulation, no explanation is being offered for the persistent presence of fibrin deposits in the affected organs. A classic example is stroke, in which the thrombolytic therapy is effective only during the first 3-4 h after the onset of thrombosis. This phenomenon can now be explained in terms of the modification of fibrinogen structure induced by hydroxyl radicals generated during the period of ischemia caused, in turn, by the blocking of the blood flow within the obstructed vessels. Fibrinogen modification involves intra-to intermolecular disulfide rearrangement induced by the reductive power of hydroxyl radicals that result in the exposition of buried hydrophobic epitopes. Such epitopes react readily with each other forming linkages stronger than the peptide covalent bonds, thus rendering them resistant to the proteolytic degradation. Also, limited reduction of human serum albumin (HSA) generates hydrophobic polymers that form huge insoluble complexes with fibrinogen. Consequently, such insoluble copolymers can be deposited within the circulation of various organs leading to their dysfunction. In conclusion, the study of protein hydrophobic interactions induced by a variety of nutritional and/or environmental factors can provide a rational explanation for a number of pathologic conditions including cardiovascular, neurologic, and other degenerative diseases including cancer.

Topics: Animals; Arthritis; Cardiovascular Diseases; Diabetes Mellitus; Fibrin; Fibrinogen; Fibrinolysis; Humans; Hydrophobic and Hydrophilic Interactions; Kidney Diseases; Lung Diseases; Models, Biological; Neoplasms; Nervous System Diseases; Polymerization; Protein Interaction Domains and Motifs; Serum Albumin, Human; Solubility; Thrombosis

Urinary sediments may be associated with the pathogenesis of renal diseases. It is important to examine the presence of dysmorphic red blood cells, macrophages, tubular epithelial cells, fibrin casts, glomerular epithelial cells, and ammonium acid urate crystals in urine for evaluating the clinical status of glomerulonephritis. Collecting evidence regarding the relationship between urinary sediments and renal disease activity may provide cost-effective and prompt clinical information to improve clinical practice.

Topics: Crystallization; Epithelial Cells; Erythrocytes; Fibrin; Humans; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Macrophages; Podocytes; Uric Acid; Urinalysis

Topics: Anticoagulants; Dipyridamole; Fibrin; Humans; Kidney Diseases; Platelet Activation; Platelet Aggregation Inhibitors; Receptor, PAR-1; Receptor, PAR-2; Signal Transduction; Thrombophilia; Warfarin

Fibrinogen, a 340-kDa plasma protein, is composed of two identical molecular halves each consisting of three non-identical A alpha-, B beta- and gamma-chain subunits held together by multiple disulfide bonds. Fibrinogen is shown to have a trinodular structure; that is, one central nodule, the E domain, and two identical outer nodules, the D-domains, linked by two coiled-coil regions. After activation with thrombin, a pair of binding sites comprising Gly-Pro-Arg is exposed in the central nodule and combines with its complementary binding site a in the outer nodule of another molecules. By using crystallographic analysis, the alpha-amino group of alpha Gly-1 is shown to be juxtaposed between gamma Asp-364 and gamma Asp-330, and guanidino group of alpha Arg-3 between the carboxyl group of gamma Asp-364 and gamma Gln-329 in the a site. Half molecule-staggered, double-stranded protofibrils are thus formed. Upon abutment of two adjacent D domains on the same strand, D-D self association takes place involving Arg-275, Tyr-280, and Ser-300 of the gamma-chain on the surface of the abutting two D domains. Thereafter, carboxyl-terminal regions of the alpha-chains are untethered and interact with those of other protofibrils leading to the formation of thick fibrin bundles and networks. Although many enigmas still remain concerning the exact mechanisms of these molecular interactions, fibrin assembly proceeds in a highly ordered fashion. In this review, these molecular interactions of fibrinogen and fibrin are discussed on the basis of the data provided by hereditary dysfibrinogens on introducing representative molecules at each step of fibrin clot formation.

Topics: Amino Acid Sequence; Amyloidosis; Base Sequence; Fibrin; Fibrinogen; Humans; Kidney Diseases; Microscopy, Electron, Scanning; Molecular Sequence Data

Topics: Animals; Fibrin; Humans; Kidney Diseases; Kidney Glomerulus; Thromboplastin

Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Arteriosclerosis; Dogs; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Humans; Kidney Diseases; Neoplasms; Pregnancy; Pregnancy Complications; Radioimmunodetection; Thrombosis

Glomerular fibrin deposits may occur within vessels or in extracapillary crescents. Studies suggest that intravascular thrombosis is promoted by endothelial cell activation/injury, resulting in the release of endothelial-cell-derived tissue factor procoagulant, fibrinolytic inhibitors, platelet activating factor, and large multimers of von Willebrand factor. Fibrin in crescents may arise from coagulation of plasma in Bowman's space mediated by the release of tissue factor from infiltrating macrophages. Glomerular fibrin may be removed by fibrinolytic or phagocytic mechanisms or persist and lead to glomerular obsolescence. Suppression or elimination of factors that promote glomerular fibrin deposition and enhancement of mechanisms that remove glomerular fibrin may be important in the recovery from several forms of human kidney disease.

Topics: Animals; Blood Coagulation; Disease Models, Animal; Fibrin; Fibrinolysis; Humans; Kidney Diseases; Kidney Glomerulus

A role for coagulation in renal diseases is suggested by the presence of glomerular fibrin deposits in numerous experimental and human renal diseases, some of which are of toxic origin. Fibrin may exert detrimental effects by occluding glomerular capillaries, by attracting macrophages or by direct cytotoxicity to mesangial cells. Intraglomerular fibrin deposition or formation may result in part from changes in the normal multiple haemostatic properties of glomeruli. In glomerular clotting of systemic origin, e.g., glycerol-induced acute renal failure with intravascular coagulation, inhibition by drugs of glomerular fibrinolytic activity leads to persistent thrombi and permanent renal damage. In immune glomerulonephritis, fibrin formation may depend on activation of glomerular prothrombotic properties: for example, glomerular procoagulant (tissue factor-like) activity is enhanced at the peak of mercuric chloride-induced autoimmune glomerulonephritis, characterized by massive fibrin deposits. Finally, fibrin deposits probably contribute to the progressive renal lesions and chronic renal failure seen in rats with kidney damage, in which anticoagulant therapy has a beneficial effect.

Topics: Animals; Blood Coagulation; Fibrin; Fibrinolysis; Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Glomerulus

Topics: Animals; Fibrin; Fibrinolysin; Fibrinolysis; Heparin; Humans; Kidney Diseases; Urologic Diseases; Urologic Neoplasms

Topics: Animals; Blood Coagulation; Fibrin; Fibrinolysis; Hemostasis; Humans; Kidney Diseases; Kidney Glomerulus; Thrombosis

The fibrinolytic system comprises a proenzyme, plasminogen, which can be activated to the active enzyme plasmin, that will degrade fibrin by different types of plasminogen activators. Inhibition of fibrinolysis may occur at the level of plasmin or at the level of the activators. Fibrinolysis in human blood seems to be regulated by specific molecular interactions between these components. In plasma, normally no systemic plasminogen activation occurs. When fibrin is formed, small amounts of plasminogen activator and plasminogen adsorb to the fibrin, and plasmin is generated in situ. The formed plasmin, which remains transiently complexed to fibrin, is only slowly inactivated by alpha 2-antiplasmin, while plasmin, which is released from digested fibrin, is rapidly and irreversibly neutralized. The fibrinolytic process, thus, seems to be triggered by and confined to fibrin. Thrombus formation may occur as the result of insufficient activation of the fibrinolytic system and (or) the presence of excess inhibitors, while excessive activation and/or deficiency of inhibitors might cause excessive plasmin formation and a bleeding tendency. Evidence obtained in animal models suggests that tissue-type plasminogen activator, obtained by recombinant DNA technology, may constitute a specific clot-selective thrombolytic agent with higher specific activity and fewer side effects than those currently in use.

Topics: alpha-2-Antiplasmin; alpha-Macroglobulins; Animals; Behcet Syndrome; Binding Sites; Disseminated Intravascular Coagulation; Embolism; Female; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; In Vitro Techniques; Kidney Diseases; Kinetics; Liver Diseases; Lysine; Plasminogen; Plasminogen Activators; Plasminogen Inactivators; Pregnancy; Streptokinase; Thrombosis; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

The existence of a system in the human body capable of inducing the dissolution of endogenous pathologically formed thrombi was appreciated in ancient times. Considered in detail in this article are the data that have elucidated the physiologic regulation of which plasmin formation is dependent on, the plasma concentration of plasminogen, availability of activators of plasminogen in the plasma and surrounding tissue environment, the concentration of naturally present inhibitors, and the existence of fibrin in the circulation. Important in this rapidly progressive scientific discipline is consideration of the factors which control the synthesis of the components of this proteolytic enzyme system. Recently abundant information has indicated that this plasminogen-plasmin proteolytic enzyme system can be utilized therapeutically. Knowledge of the mechanisms of this system has permitted identification of agents that can be exogenously administered to releave thrombotic obstruction to blood flow in the venous (pulmonary emboli, deep vein thrombosis) and arterial (peripheral and central vessels) circulatory systems. Particularly important is the demonstration that thrombolytic agents can directly attack and alleviate the immediate cause of acute myocardial infarction. As a result of the innovations in the present decade, it is evident that the plasminogen system can be advantageously employed to reverse the pathologic effects of all thrombotic diseases.

Topics: alpha 1-Antitrypsin; alpha-2-Antiplasmin; alpha-Macroglobulins; Antifibrinolytic Agents; Antithrombin III; Arterial Occlusive Diseases; Arteriosclerosis; Complement C1 Inactivator Proteins; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; Kidney Diseases; Liver Diseases; Myocardial Infarction; Neoplasms; Plasminogen; Pulmonary Embolism; Thrombophlebitis

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Blood Vessels; Cardiopulmonary Bypass; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Infant, Newborn; Kidney Diseases; Myocardial Infarction; Neoplasms; Pregnancy; Pulmonary Embolism; Syndrome; Thrombin; Thrombophlebitis; Thrombosis

Topics: Adult; Afibrinogenemia; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Chemical Phenomena; Chemistry; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Infant, Newborn; Kidney Diseases; Liver Diseases; Male; Models, Biological; Pregnancy

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

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: Acute Kidney Injury; Angiotensin II; Animals; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Catecholamines; Disseminated Intravascular Coagulation; Female; Fibrin; Heparin; Humans; Hypertension, Renal; Kidney Diseases; Kidney Glomerulus; Pre-Eclampsia; Pregnancy; Renin; Thrombosis; Uremia

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: Animals; Anticoagulants; Autoimmune Diseases; Blood Coagulation Disorders; Disease Models, Animal; Fibrin; Heparin; Humans; Kidney; Kidney Cortex Necrosis; Kidney Diseases; Kidney Glomerulus; Mice; Nephritis; Rabbits; Shwartzman Phenomenon; Thrombosis

Topics: Adenine Nucleotides; Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Clot Retraction; Collagen; Fibrin; Fibrinogen; Hemostasis; Kidney Diseases; Liver Diseases; Platelet Adhesiveness; Thrombocytopenia; Thrombocytosis

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

A clinical trial was undertaken to study endotoxemia in 14 patients with obstructive jaundice given the antiendotoxin polymyxin B, 13 patients with obstructive jaundice who were not given the antiendotoxin , and 13 nonjaundiced control patients undergoing comparable surgery. Endotoxins were detected by the limulus assay. Endotoxemia did not occur in the nonjaundiced patients but was common before (68 percent), during (70 percent), and after (81 percent) surgery in the jaundice patients. Thirty-six percent of the jaundiced patients had postoperative oliguria. Endotoxemia before surgery was associated with death after surgery, all deaths occurring in patients who were endotoxemic before operation (p less than 0.05). Polymyxin B infusion had no effect on endotoxemia or outcome. Measurement of indicators of fibrinolysis, soluble fibrin, and fibrin degradation products showed no prognostic significance. We conclude that preoperative endotoxemia is an important predictor of outcome in patients who undergo surgery for jaundice.

Topics: Bilirubin; Cholestasis; Clinical Trials as Topic; Endotoxins; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Kidney Diseases; Middle Aged; Polymyxin B; Polymyxins; Postoperative Complications

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

The Moncrief-Popovich technique of peritoneal catheter implantation has beneficial effects for peritoneal dialysis (PD) initiation. However, it might increase the risk of peritoneal catheter obstruction by fibrin clots, because the catheter is buried under the skin for several weeks to months. Effects of treatment of intraluminal occlusion of PD catheters with tissue plasminogen activator, recommended by the International Society for Peritoneal Dialysis guidelines/recommendations are reportedly limited. We investigated the effectiveness of the 'alpha-replacer' (JMS, Tokyo, Japan) for PD catheter obstruction.. We retrospectively analyzed a total of 193 patients in whom PD was initiated. PD catheters were embedded using the Moncrief-Popovich technique in 130 of these patients. We assessed the occurrence rates of peritoneal catheter obstruction and the utility of the alpha-replacer for treating intraluminal catheter occlusion by fibrin clots.. Catheter obstruction occurred in eight cases with embedded catheters, one due to omental wrapping and the others due to fibrin clots, in which median catheter burial durations were 477 (interquartile range [IQR], 226-510) days. All catheter obstructions due to fibrin clots were successfully treated with the alpha-replacer, leading to improved catheter drainage. The median amount of contrast agent used in catheterography was 10 (IQR 9-10) mL, which did not adversely affect residual renal function. There were no complications. No recurrence occurred during the observation period (median 111, IQR 55.5-141 months).. Our results suggest that treatment with the alpha-replacer is a safe and effective treatment option for intraluminal obstruction of PD catheters by fibrin clots.

Topics: Adult; Aged; Catheter Obstruction; Catheterization; Catheters, Indwelling; Equipment Design; Female; Fibrin; Humans; Kidney Diseases; Male; Middle Aged; Peritoneal Dialysis; Radiography, Interventional; Retrospective Studies; Time Factors; Treatment Outcome

Hypercoagulability is associated with chronic kidney disease (CKD). Tissue factor/factor VIIa complex and factor Xa in the coagulation cascade are known to activate protease-activated receptor 2 (PAR2), and to cause inflammation and tissue injury. Although PAR2 is highly expressed in the kidney, it is unclear whether PAR2 plays a pathogenic role in CKD. To test this, we fed the mice lacking Par2 (F2rl1

Topics: Adenine; Animals; Enzyme-Linked Immunosorbent Assay; Factor V; Factor Xa; Fibrin; Fibrosis; Gene Expression Regulation; Inflammation; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Oxidative Stress; Receptor, PAR-2; Renal Insufficiency, Chronic; Thromboplastin

Cisplatin (cis-diammine dichloroplatinum (II), CDDP) is a widely used drug for treatment of various types of cancers. However, CDDP-induced nephrotoxicity remains the main dose-limiting side effect. Retinoids are a group of vitamin A-related compounds that exert their effects through retinoid receptors activation. In this study, we investigated the effect of CDDP treatment on retinoic acid receptor-α (RAR-α) and retinoid X receptor-α (RXR-α) expression. In addition, we investigated the possible modulatory effects of RAR agonist, all-trans retinoic acid (ATRA), on CDDP-induced nephrotoxicity. Rats were treated with saline, DMSO, CDDP, ATRA, or CDDP/ATRA. Twenty-four hours after the last ATRA injection, rats were killed; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CDDP treatment significantly increased serum levels of creatinine and urea, with concomitant decrease in serum albumin. Moreover, reduced glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities were significantly reduced with concurrent increase in kidney malondialdehyde (MDA) content following CDDP treatment. Furthermore, CDDP markedly upregulated tubular RAR-α, RXR-α, fibrin, and inducible nitric oxide synthase (iNOS) protein expression. Although administration of ATRA to control rats did not produce marked alterations in kidney function parameters, administration of ATRA to CDDP-treated rats significantly exacerbated CDDP-induced nephrotoxicity. In addition, CDDP/ATRA co-treatment significantly increased RAR-α, RXR-α, fibrin, and iNOS protein expression compared to CDDP alone. In conclusion, we report, for the first time, the crucial role of retinoid receptors in CDDP-induced nephrotoxicity. Moreover, our findings indicate that co-administration of ATRA with CDDP, although beneficial on the therapeutic effects, their deleterious effects on the kidney may limit their clinical use.

Topics: Animals; Antineoplastic Agents; Cisplatin; Drug Synergism; Fibrin; Kidney; Kidney Diseases; Male; Nitric Oxide Synthase Type II; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Retinoid X Receptors; Signal Transduction; Tretinoin

Staphylococcus aureus is a frequent cause of skin infection and sepsis in humans. Preclinical vaccine studies with S. aureus have used a mouse model with intraperitoneal challenge and survival determination as a measure for efficacy. To appreciate the selection of protective antigens in this model, we sought to characterize the pathological attributes of S. aureus infection in the peritoneal cavity. Testing C57BL/6J and BALB/c mice, >10(9) CFU of S. aureus Newman were needed to produce a lethal outcome in 90% of animals infected via intraperitoneal injection. Both necropsy and histopathology revealed the presence of intraperitoneal abscesses in the vicinity of inoculation sites. Abscesses were comprised of fibrin as well as collagen deposits and immune cells with staphylococci replicating at the center of these lesions. Animals that succumbed to challenge harbored staphylococci in abscess lesions and in blood. The establishment of lethal infections, but not the development of intraperitoneal abscesses, was dependent on S. aureus expression of alpha-hemolysin (Hla). Active immunization with nontoxigenic Hla(H35L) or passive immunization with neutralizing monoclonal antibodies protected mice against early lethal events associated with intraperitoneal S. aureus infection but did not affect the establishment of abscess lesions. These results characterize a mouse model for the study of intraperitoneal abscess formation by S. aureus, a disease that occurs frequently in humans undergoing continuous ambulatory peritoneal dialysis for end-stage renal disease.

Topics: Abscess; Animals; Antibodies, Neutralizing; Bacterial Toxins; Collagen; Disease Models, Animal; Female; Fibrin; Hemolysin Proteins; Kidney Diseases; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Peritonitis; Staphylococcal Infections; Staphylococcus aureus

Glomerular fibrin thrombi may be an early indication of antibody-mediated rejection in renal allograft biopsies. However, fibrin thrombi have a broad differential; thus, we sought to evaluate the etiology and implications of glomerular fibrin thrombi in allograft biopsies of blood group and cytotoxic crossmatch compatible renal allografts. Biopsies were identified from the pathology files of Oregon Health & Science University. Detailed histopathologic findings were retrospectively correlated with clinical data, treatment, and outcome. Sixteen early posttransplant biopsies had glomerular fibrin thrombi, including three surveillance biopsies. Six of 16 biopsies had no other histopathologic findings; 5/16 had glomerulitis and peritubular capillaritis; 4/16 had concomitant cellular vascular rejection; one had parenchymal infarction. C4d staining was positive in 4/16 cases. Most patients were treated with IVIg and plasmapheresis, others with rapamycin, thymoglobulin, or rituximab. At an average follow-up of 62 months, 8 patients with functioning grafts had a mean serum creatinine of 1.4 mg/dL (122 μmol/L). Antibody-mediated rejection is an important consideration in blood group compatible allograft biopsies with glomerular fibrin thrombi, even with C4d-negative biopsies. However, multidisciplinary evaluation is necessary, given other etiologies, including drug toxicity, hemolytic-uremia syndrome, and large vessel thrombosis. Despite aggressive treatment, both short and long-term graft survival may be compromised.

Topics: ABO Blood-Group System; Biopsy; Blood Grouping and Crossmatching; Complement C4b; Fibrin; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Immunosuppression Therapy; Inflammation; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Peptide Fragments; Thrombosis; Thrombotic Microangiopathies; Time Factors; Transplantation, Homologous; Treatment Outcome

Interstitial fibrosis is a universal feature of progressive kidney disease. Urokinase-type plasminogen activator (uPA) is thought to participate for several reasons: 1) uPA is produced predominantly in kidney, 2) its inhibitor plasminogen activator inhibitor-1 (PAI-1) is a strong promoter of interstitial fibrosis, whereas its receptor (uPAR) attenuates renal fibrosis, 3) uPA reduces fibrosis in liver and lung, and 4) uPA can activate hepatocyte growth factor (HGF), a potent antifibrotic growth factor. The present study tested the hypothesis that endogenous uPA reduces fibrosis severity by investigating the unilateral ureteral obstruction (UUO) model in wild-type (WT) and uPA-/- mice. Several outcomes were measured: renal collagen 3-21 days after UUO, macrophage accumulation (F4/80 Western blotting), interstitial myofibroblast density (alpha-smooth muscle actin immunostaining), and tubular injury (E-cadherin and Ksp-cadherin Western blotting). None of these measures differed significantly between WT and uPA-/- mice. uPA genetic deficiency was not associated with compensatory changes in renal uPAR mRNA levels, PAI-1 protein levels, or tissue plasminogen activator activity levels after UUO. Despite the known ability of uPA to activate latent HGF, immunoblotting failed to detect significant differences in levels of the active HGF alpha-chain and phosphorylated cMET (the activated HGF receptor) between the WT and uPA-/- groups. These findings suggest that the profibrotic actions of PAI-1 are uPA independent and that an alternative pathway must activate HGF in kidney. Finally, these results highlight a significant organ-specific difference in basic fibrogenic pathways, as enhanced uPA activity has been reported to attenuate pulmonary and hepatic fibrosis.

Topics: Animals; Blotting, Western; Collagen; Disease Progression; Fibrin; Fibroblasts; Fibrosis; Genotype; Hepatocyte Growth Factor; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Peptide Hydrolases; Phenotype; Phosphorylation; Plasminogen Activators; RNA, Messenger; Ureteral Obstruction; Urokinase-Type Plasminogen Activator

Cell and gene therapy may alter the outcome of renal diseases, such as hereditary nephropathies, acute and chronic glomerulonephritis and allograft nephropathy. However, owing to blockade of many viral and cellular vehicles by the complex glomerular architecture, the exact nature of gene and cell delivery into specific renal compartments remains currently unknown. To study the interaction of viral vectors with a variety of renal cells and mesenchymal stem cells (MSCs), we employed a novel biological three-dimensional (3D) matrix comprised of fibrin microbeads (FMB) in comparison to monolayer cell culture. Our studies showed that renal cells of both established and primary lines can grow efficiently on FMB and differentiate into epithelial structures, as shown by electron microscopy. Gene delivery into renal cells in 3D was observed for several viral vectors and growth in 3D on FMB conferred resistance to renal cancer cells in the context of oncolytic adenoviruses. Finally, MSCs from various rodent species attached to FMB, grew robustly, survived for several weeks and could efficiently be transduced on FMB. Thus, on the basis of growth, differentiation and transduction of renal cells in 3D, FMB emerge as a novel 3D cellular microenvironment that differs substantially from monolayer cell cultures.

Topics: Cell Differentiation; Cell Line; Cell Proliferation; Cell Survival; Fibrin; Genetic Therapy; Humans; Kidney; Kidney Diseases; Kidney Neoplasms; Mesenchymal Stem Cells; Microscopy, Electron; Microspheres; Oncolytic Viruses

Scleroderma renal crisis (SRC) can lead to end-stage renal disease (ESRD) and subsequent need for dialysis and/or renal transplantation. We review all reported cases of renal transplantations in scleroderma patients from PubMed search, present UNOS data on transplant outcomes, and identify predictors for allograft SRC. Of the five cases with recurrent SRC, all developed ESRD within a year of onset of native kidney SRC, whereas none of those who developed ESRD more than 1-2 years after the onset of SRC developed recurrence. Anemia preceded allograft SRC in two cases, pericardial effusion in one, and skin tightening in two others. UNOS data (October 1987-July 2004) documented 260 transplants performed for the renal diagnosis of scleroderma, with a 5-year graft survival rate of 56.7%. The risk for allograft SRC recurrence appears to correlate with early native renal function loss following the onset of SRC. Recurrent SRC in the allograft may be heralded by multiple clinical markers known to be predictive of severe scleroderma, including progression of diffuse skin thickening, new-onset anemia and cardiac complications.

Topics: Anemia; Arterioles; Autoimmune Diseases; Disease Progression; Edema; Female; Fibrin; Graft Rejection; Graft Survival; Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Transplantation; Kidney Tubules; Leukocytes, Mononuclear; Lymphocytes; Middle Aged; Pericardial Effusion; PubMed; Recurrence; Renal Dialysis; Risk Factors; Scleroderma, Systemic; Skin; Thrombosis; Time Factors; Transplantation, Homologous

The increasing shortage of cadaver donor kidneys has prompted the use of expanded or marginal donor kidneys, ie, from older donors or those with a history of hypertension or diabetes. These marginal kidneys may be especially susceptible to calcineurin inhibitor (CNI)-mediated vasoconstriction and nephrotoxicity. Recipients of renal transplants from marginal donors therefore require non-nephrotoxic immunosuppression. Some investigators have proposed using sirolimus, a novel and potent immunosuppressant, instead of CNIs. Moreover, another complication of solid-organ transplantation is thrombotic microangiopathy (TMA), which affects 3% to 14% of patients on immunosuppression therapy treated with CNIs. Therefore, it was suggested that CNIs may be substituted by sirolimus in patients with posttransplantation CNI-induced TMA. We report 3 patients who received marginal cadaveric kidneys and were administered maintenance immunosuppression with sirolimus, prednisone, and mycophenolate mofetil. They each developed de novo TMA despite never having been previously administered a CNI. In these cases, TMA occurred in marginal kidneys with possible endothelial injury before transplantation. Sirolimus may have prevented recovery from these injuries and thus may have promoted TMA in these marginal kidneys. The risk for such a vascular complication should be kept in mind in patients who receive marginal kidneys and are administered sirolimus, even when sirolimus is used without CNIs.

Topics: Aged; Arterioles; Biopsy; Drug Therapy, Combination; Endothelium, Vascular; Female; Fibrin; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Male; Microcirculation; Middle Aged; Mycophenolic Acid; Organ Preservation; Prednisone; Sirolimus; Thrombosis; Tissue and Organ Harvesting; Transplants

Various topical hemostatic agents or devices have been employed to address the challenges associated with hemorrhage from parenchymal organs during surgery or trauma. Their relative efficacy, however, has not been assessed in a single animal model. The objective of this study was to develop a small animal renal hemorrhage model for comparing hemostatic efficacy of various topical agents, and then to compare fibrin sealant (FS) to an existing standard of care for topical hemostasis. A left heminephrectomy was performed in anesthetized adult male Sprague-Dawley rats. Animals were anticoagulated with 2000 IU/kg heparin IV and various topical hemostatic agents were applied to the injury. Treatment groups included FS applied as a spray; FS applied through a cannula; gelatin sponge (GS) soaked in 1000 IU/mL thrombin solution; GS soaked in 300 IU/mL thrombin; dry GS; and fibrinogen without thrombin applied as a spray. The main endpoints of the study were incidence of hemostasis, blood loss, acute survival trends, and maintenance of mean arterial pressure (MAP). Three treatment groups, the two FS groups and the GS soaked in 1000 IU/mL thrombin, afforded significant hemostasis compared to the controls (P < 0.01). Both FS groups had significantly less blood loss, longer survival times, and maintained higher MAPs than the GS-treated groups. Quantitative dose effects and functional deficiencies in topical hemostatic products could be assessed using this animal model. The study demonstrated that liquid FS was significantly more efficacious than a GS soaked in thrombin for abating hemorrhage from a renal excision in a heparinized rat.

Topics: Administration, Topical; Animals; Disease Models, Animal; Fibrin; Hemorrhage; Hemostatics; Heparin; Kidney Diseases; Male; Nephrectomy; Rats; Rats, Sprague-Dawley; Renal Circulation; Thrombin; Time Factors

1Alpha,25-dihydroxyvitamin D3 (active form of vitamin D3; vitamin D3) has been reported to induce the upregulation of thrombomodulin and downregulation of tissue factor (TF) on monocytes. The possibility exists that vitamin D3 prevents the development of disseminated intravascular coagulation (DIC). In particular, monocyte TF production plays an important role in the pathophysiology of DIC in septic patients. We have attempted to determine whether vitamin D3 is effective against DIC in a rat model induced by lipopolysaccharides (LPS) (30 mg/kg, 4 h) or TF (3.75 U/kg, 4 h) using selective hemostatic parameters, markers of organ dysfunction and pathological findings (assessment of glomelular fibrin deposition). Vitamin D3 was administered orally each day at a dose of 2.0 mg/kg/day for 3 days, or low molecular weight heparin (LMWH 200 u/kg; i.v.) was given 10 min before the injection of TF or LPS in each treatment group. Vitamin D3 was effective against DIC in the rat model induced by LPS only, whereas LMWH was effective against DIC in both rat models induced by either TF or LPS. The anti-DIC effect of vitamin D3 was equal to (or more potent than) that of LMWH. The results suggested that vitamin D3 was useful for the treatment of LPS-induced DIC, and that the assessment of a drug's efficacy should be done carefully given the markedly different results obtained according to the agents used to induce DIC.

Topics: Administration, Oral; Animals; Anticoagulants; Cholecalciferol; Coagulants; Disease Models, Animal; Disseminated Intravascular Coagulation; Fibrin; Heparin; Kidney Diseases; Kidney Glomerulus; Lipopolysaccharides; Male; Rats; Rats, Wistar; Sepsis; Thromboplastin; Thrombosis

The impact of clot stability affecting the vasculopathy and tissue necrosis in Shwartzman reaction was investigated using plasma Factor XIII A2-depleted rabbit (FXIII-DR). Plasma Factor XIIIA2 (FXIIIA2) was depleted by infusion of the mono-specific goat anti-rabbit FXIIIA2 IgG. Generalized Shwartzman reaction (GSR) was induced by priming and challenged by i.v. injection of LPS and local Shwartzman reaction (LSR) was primed by intradermal injection of LPS and challenged by i.v. injection of LPS. Histological examination of the GSR animals showed, extensive thrombi accumulation in renal tubules and bilateral cortical necrosis of kidney in 8 out of 10 rabbits but none in the FXIII-DR. Fibrinogen levels were elevated to 3 approximately 4 fold at 24 h and lowered at 48 h whereas a steady rise was seen in the FXIII-DR. FDP levels in GSR animals were significantly elevated at 24 h and further increased at 48 h but only slightly elevated in the FXIII-DR. Examination of the LSR tissues after 48 h showed an acute onset of progressive cutaneous vascular thrombosis, purpura, and secondary hemorrhagic necrosis whereas neither fibrin deposit nor necrosis of tissue were detected in FXIII-DR despite of an early edema formation. Fibrinogen levels were also increased two fold at 24 h but returned to basal levels at 48 h in control LSR animals but not affected at all in FXIII-DR. These results suggest that during the severe inflammatory conditions such as sepsis, the fibrinolytic system is functionally sufficient to dissipate the pathogenic accumulation of disseminated intravascular clots and exudated fibrin clots if those clots were prevented from getting crosslinked in plasma.

Topics: Animals; Antibodies, Monoclonal; Disease Models, Animal; Disseminated Intravascular Coagulation; Factor XIII; Factor XIII Deficiency; Fibrin; Fibrinogen; Kidney; Kidney Diseases; Lipopolysaccharides; Necrosis; Plasminogen; Rabbits; Sepsis; Shwartzman Phenomenon; Skin; Skin Diseases

Chronic allograft nephropathy (CAN), the major cause of renal graft failure, frequently displays extensive interstitial fibrin deposition. Little is known in regard to the cause of the altered coagulation/fibrinolysis balance and its relevance in the pathogenesis of CAN. Thrombin, present within the fibrin clots, can interact with a specific receptor, protease-activated receptor 1 (PAR-1), and modulate a variety of cell functions. On the other hand, the derangement of the fibrinolytic system may directly affect extracellular matrix (ECM) degradation.. In the present study, we investigated, by in situ hybridization, PAR-1 gene expression and the mRNA levels for tissue factor and plasminogen activator inhibitor 1 (PAI-1), two key regulatory molecules of coagulation and fibrinolysis, in 16 CAN biopsies and in 10 normal human kidney grafts. The thrombin-induced transforming growth factor beta (TGF-beta) gene and protein expression in proximal tubular cells (PTC) was investigated by Northern blotting and ELISA, respectively.. Fibrin deposits, absent in normal grafts, were observed in the interstitial space and arterial wall of CAN. Tissue factor gene expression was not increased either at the vascular or at the interstitial level in CAN. On the contrary, PAI-1 gene expression, barely detectable in control tissue, was strikingly increased in CAN, with a distribution resembling the pattern of fibrin deposition. Note that PAI-1 gene expression was directly correlated with the degree of interstitial fibrosis. In addition, fibrin deposits were strictly associated with a marked increase of PAR-1 gene expression in endothelial cells and PTC. The tubular expression of PAR-1 was significantly higher in Banff grade II-III than in grade I. In vitro, incubation of PTC with thrombin caused a significant up-regulation of TGF-beta gene expression, followed by an increased TGF-beta release into the supernatant. Interestingly, urine from CAN patients contained significantly higher levels of TGF-beta.. Fibrin deposits in CAN may result from the increased expression of PAI-1 and the subsequent inhibition of fibrinolysis. The reduced fibrinolysis may cause, in turn, a decreased ECM turnover. Finally, thrombin, preserved in the active form within the fibrin clots, may interact with PAR-1 highly expressed on PTC and induce an up-regulation of ECM deposition in a TGF-beta-dependent manner.

Topics: Chronic Disease; Extracellular Matrix; Fibrin; Fibrinolysis; Humans; Kidney; Kidney Diseases; Kidney Transplantation; Plasminogen Activator Inhibitor 1; Receptor, PAR-1; Receptors, Thrombin; RNA, Messenger; Transforming Growth Factor beta; Transplantation, Homologous

Leukocytoclastic vasculitis is defined by histologic features and can be observed in a wide range of entities. Independent of the causative disease, extracutaneous complications are frequent, mainly in the kidneys and gastrointestinal tract. It has been suggested that the severity of histological changes could correlate with the clinical course of the disease. We have therefore compared the severity of histological changes of leukocytoclastic vasculitis to clinical and laboratory findings indicative of extracutaneous involvement in a large group of patients. Among 289 patients followed for cutaneous vasculitis, we included 184 patients with purpuric papules and proven leukocytoclastic vasculitis who all had standardized investigations. A cutaneous biopsy was performed early and standardized laboratory investigations were carried out. The slides were retrospectively randomized and the depth of vasculitis and severity of vascular necrosis were determined according to a semiquantitative scale. These data were compared to the renal, gastrointestinal and articular symptoms using Fischer's exact test, Chi-square test and variance analysis. The intensity of vascular necrosis and the depth of vasculitis were no more severe in patients having renal changes, gastrointestinal involvement or articular symptoms. Both variance analysis and Chi-square tests failed to show a significant increase in the severity score in patients having extracutaneous complications. In this study, the severity of histopathological changes was not predictive of extracutaneous involvement. Thus it appears that the degree of involvement of the cutaneous vessels probably does not correlate with that of vessels in visceral organs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Fibrin; Gastrointestinal Diseases; Humans; Joint Diseases; Kidney Diseases; Male; Middle Aged; Necrosis; Prognosis; Random Allocation; Severity of Illness Index; Skin Diseases, Vascular; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Antibodies, Monoclonal; Epitopes; Fibrin; Fibrinolysin; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Kidney Diseases; Kidney Glomerulus; Microscopy, Immunoelectron

Six cases of malignancy-associated thrombotic microangiopathy and eight cases of idiopathic microangiopathy have been studied by renal biopsy. All patients of both groups had mild to severe renal impairment and microangiopathic hemolytic anemia. The renal lesions were histopathologically identical in the two groups. The most characteristic abnormalities were glomerular mesangiolysis and glomerular and arteriolar thrombosis. Subendothelial widening, presumably due to entrapment of blood components, and the formation of capillary and arteriolar thrombi may be attributed to endothelial damage. Glomerular fibrinogen was demonstrated by immunofluorescence in a majority of cases. Immunofluorescence also showed glomerular immunoglobulin M (IgM) and Clq in a majority of cases and C3 in slightly less than half. Mesangiolysis, present in every case, resulted in coalescence of capillary lumina, but mesangiolysis is a bland process, easily overlooked. The mesangial waists of the glomerular tufts seemed to unravel and come apart, with no inflammatory reaction or fibrin deposition on the luminal surface. The presence of capillary enlargement was confirmed morphometrically as an increased proportion of glomerular sectional area. In what appeared to be a late stage of mesangiolysis, the mesangium was thickened by pale fibrillary material, producing a lobulated glomerular tuft and eventual glomerular solidification. The early stages of mesangiolysis may be reflected only in glomerular capillary ectasia, whereas the late stages produce a distinctive form of glomerular sclerosis.

Topics: Adult; Aged; Anemia, Hemolytic; Biopsy; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerular Mesangium; Humans; Kidney Diseases; Male; Middle Aged; Thrombosis

The persistency of fibrin deposits in the kidney during renal diseases could reflect either a defective release of plasminogen activators (PA) or a local excess of PAI. In order to investigate this question, we studied human renal biopsies by immunofluorescence technique with specific antibodies for fibrin, tissue-type plasminogen activator (t-PA), urokinase (u-PA), PAI-1 and PAI-2. By this technique t-PA could be detected in the glomerular flocculus and the endothelium of small arteries of the normal control kidneys. We failed to detect significant fluorescence with other antibodies in normal kidneys. Conversely, in cases of vascular nephropathy with thrombosis the positive fluorescence obtained with anti-fibrin antibodies at the site of thrombosis was associated with a positive fluorescence with anti-PAI-1 and to a lesser extent with anti-t-PA antibodies. u-PA and PAI-2 were not detected in these lesions. Similarly in the most severe forms of crescentic glomerulonephritis, extracapillary fibrin deposits were associated with PAI-1. In one case u-PA was also detected. This is in agreement with our previous findings that glomerular epithelial cells release both PAI-1 and the inactive form of u-PA (pro u-PA). Thus, our results support the hypothesis that PAI-1, which is able to inhibit both t-PA and u-PA, may play a major role in the persistency of fibrin deposits in the human kidneys during pathological conditions.

Topics: Female; Fibrin; Fluorescent Antibody Technique; Humans; Kidney; Kidney Diseases; Male; Plasminogen Inactivators; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

To investigate the mechanisms which may influence fibrin deposition in the remnant kidney, glomerular morphology and the haemostatic properties of isolated glomeruli were assessed in two groups of rats, 30 days after surgical removal of three-quarters of the total renal parenchyma, and compared to glomeruli in sham-operated controls. One group was given the thromboxane synthetase inhibitor OKY 046 and the other was not. Fibrin deposition occurred in about 20% of glomeruli, of which 4% exhibited segmental necrotizing lesions. Concomitantly, glomerular procoagulant activity dropped to 40% of the control level and glomerular fibrinolytic activity rose to 120-130% of this level. Inhibition of thromboxane synthesis did not affect fibrin deposition, glomerular haemostasis or the development of renal insufficiency. In an additional group of unilaterally nephrectomized rats, procoagulant activity also markedly decreased in the remaining kidney. These results indicate that in the rat remnant kidney, alterations in glomerular haemostatic properties tend to have antithrombotic effects which seem to constitute an adaptive reaction by an autacoid system to glomerular fibrin deposition.

Topics: Adaptation, Physiological; Animals; Blood Coagulation; Fibrin; Fibrinolysis; Kidney Diseases; Kidney Glomerulus; Male; Methacrylates; Rats; Rats, Inbred Strains; Thromboxane-A Synthase

The immunofluorescent localization of cross-linked fibrin (XFb) in kidneys from 87 patients with renal diseases was evaluated using a monoclonal antibody that discriminates XFb from fibrinogen and its derivatives. Glomerular deposition of XFb, along the endothelial surface and in the mesangium, was frequently observed in patients with IgA nephropathy, Henoch-Schönlein purpura nephritis (HSPN), lupus nephritis, and hemolytic uremic syndrome (HUS), which was confirmed by immunoelectron microscopy. Dual-label immunofluorescent studies showed that XFb was deposited in limited areas among the sites reactive with anti-fibrinogen antibodies; XFb was not present in the crescents, Bowman's capsule or interstitium. The localization of XFb was generally discordant with that of the platelet membrane antigen and von Willebrand factor (factor VIII-related) antigen. Subendothelial co-deposition of XFb and immunoglobulins (IgA with or without IgG) occasionally accompanying C3 was found in the glomeruli of some of the patients with IgA nephropathy and HSPN. The distribution of XFb observed by immunoelectron microscopy was similar to that of electron dense deposits. The glomerular population of monocytes/macrophages in patients with XFb deposition was similar to that of those without deposition. Urinary XFb derivatives were detected by the latex agglutination test in three of the 16 patients with glomerular XFb deposition, and in two of the 18 patients without it. These data indicate that the coagulation system is activated in the kidney of patients with IgA nephropathy, HSPN, lupus nephritis and HUS, and support the concept that glomerular fibrin deposition is associated with endothelial/subendothelial and mesangial injury. The activation of the coagulation system in IgA nephropathy and HSPN seems to be mediated by immune complexes rather than monocytes/macrophages. Determination of urinary XFb derivatives is not helpful for assessing glomerular XFb deposition.

Topics: Antibodies, Monoclonal; Complement C3; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Humans; Immunoglobulin A; Immunoglobulin G; Kidney Diseases; Kidney Glomerulus; Macrophages; Monocytes

Fibrin formation in the kidney is frequently associated with clinically-significant renal dysfunction. We therefore measured and characterized the procoagulant activity (PCA) which is present in normal kidneys and in kidneys of rabbits with the Shwartzman phenomenon induced by two injections of bacterial lipopolysaccharide (LPS; E. coli LPS 055:B5,25 micrograms/kg and 50 micrograms/kg administered 24 hrs apart with rabbits sacrificed 12 hrs after the second injection). PCA was measured in sonicated tissue by one-stage coagulation assay. In normal kidneys the amounts of PCA in the inner medulla, outer medulla and inner cortex were 18.2 +/- 3.2, 44.1 +/- 3.8 and 78.5 +/- 5.7 percent, respectively, of that in the outer cortex (N = 31). Glomeruli (purified by the iron oxide magnetic method to greater than 95 percent homogeneity) contained 21.6 +/- 8.8 arbitrary units/micrograms protein compared with tubular fragments which contained 13.9 +/- 2.6 U/micrograms protein (N = 9). In LPS-treated rabbits PCA (in units/micrograms) increased in outer cortex from 33.7 +/- 3.9 (control) to 73.4 +/- 10.4 (LPS, P less than 0.01), in inner cortex from 26.7 +/- 2.9 (control) to 83.3 +/- 17 (LPS, P less than 0.02), in outer medulla from 12.9 +/- 2.4 (control) to 54.5 +/- 16.5 (LPS, P less than 0.05), and in inner medulla from 12.2 +/- 2.4 (control) to 32.1 +/- 4.9 (LPS, P less than 0.01). Glomerular PCA increased from 21.6 +/- 8.8 (control) to 88.8 +/- 20.7 (LPS) units/micrograms (P = 0.01), while tubular fragment preparation PCA increased from 13.9 +/- 2.6 (control) to 44.6 +/- 12.7 (LPS) U/micrograms (P = 0.02) (N = 9 per group).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Coagulation; Capillaries; Escherichia coli; Fibrin; Interleukin-1; Kidney Diseases; Kidney Glomerulus; Lipopolysaccharides; Male; Rabbits; Shwartzman Phenomenon

Topics: alpha-2-Antiplasmin; Fibrin; Fibronectins; Humans; Kidney Diseases; Kidney Glomerulus

This article deals with the clinical importance of antithrombin III (AT III) in renal disease. Patients with nephrotic syndrome demonstrates a high risk of thromboembolism. A renal AT III loss is an important pathogenetic factor in these events. Patients with serumalbumin below 2.0 g/dl are mostly endangered. In patients with acute oligoanuric renal failure low AT III-levels due to consumption were often found that lead to diminished protection against intravascular coagulation processes and can therefore contribute to progression of illness. An AT III-substitution may be of some benefit in these patients. Additionally AT III was given in patients with dialysis-dependent renal failure and low levels of AT III leading to a reduced incidence of thrombosis of the extracorporeal system. Unnecessary high doses were also avoided and a minimal heparinization could be performed more efficiently in bleeding risk patients. Furthermore, AT III-levels during renal transplantation and during organ rejection are reported.

Topics: Acute Kidney Injury; Antithrombin III; Antithrombin III Deficiency; Female; Fibrin; Humans; Kidney Diseases; Nephrotic Syndrome; Pregnancy; Puerperal Disorders; Risk; Sepsis; Thromboembolism; Thrombosis

A case is reported of complete obstruction of a solitary kidney induced by epsilon-aminocaproic acid used to treat significant idiopathic bleeding. The pharmacology and complications of epsilon-aminocaproic acid are also reviewed.

Topics: Adult; Aminocaproates; Aminocaproic Acid; Fibrin; Hematoma; Hematuria; Humans; Kidney; Kidney Diseases; Male

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

Topics: Child; Child, Preschool; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Kidney Diseases; Kidney Glomerulus

Whole-blood activated coagulation time (WBACT), measured by an automated technique, was used to estimate heparin activity in 12 patients in a chronic hemodialysis program. Identical heparin doses, calculated on a body-weight basis, were given to each patient, either as a single dose before a 3.5-4 hour dialysis, or as a loading dose followed by infusion during the first 1.5-2 hours of dialysis. Each dose regimen was repeated during four consecutive dialyses. The variation in heparin activity between the four dialyses did not exceed the standard deviation of the WBACT method. This indicates that the heparin requirement between dialyses was steady. Appreciable interindividual differences in heparin activity were found, however, showing that heparin requirement cannot be determined solely on a body-weight basis. Fibrin deposits in the venous drip chamber were uncommon during the first two hours but became more frequent towards the end of dialysis, the increase being significantly more with the single-dose than with the infusion regimen. Maintenance of heparin activity at the end of dialysis was better with the infusion regimen. Prolonged heparin infusion is preferable to single-dose injection to maintain the heparin effect and prevent fibrin deposits.

Topics: Adult; Aged; Animals; Female; Fibrin; Heparin; Humans; Infusions, Parenteral; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Renal Dialysis; Swine; Thrombosis; Whole Blood Coagulation Time

Hyperacute and renal allograft failure, whether due to rejection or other mechanisms, such as perfusion injury, is usually associated with extensive intraglomerular fibrin deposition and allograft loss. Defibrination with ancrod was used to treat a patient with hyperacute renal allograft failure and extensive glomerular fibrin deposition and necrosis. The patient's plasma had normal fibrinolytic activity but a complete absence of the ability to generate prostacyclin-like activity from rat aortic endothelium "in vitro". Treatment was associated with complete recovery of renal function, disappearance of glomerular fibrin, and restoration toward normal of glomerular structure.

Topics: Adult; Ancrod; Biological Products; Biopsy; Epoprostenol; Female; Fibrin; Graft Rejection; Humans; In Vitro Techniques; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Prostaglandins

In 115 patients with various glomerular diseases and in 23 with chronic pyelonephritis the comparative incidence of glomerular fibrin deposits, and blood and urinary FDP was studied for evaluation of their clinical value. The results of the study indicate that the determination of urinary FDP is the most reliable clinico-laboratory test for the presence of increased intrarenal haemocoagulation. Moreover, the quantitative assessment of urinary FDP could be also used as an index for estimating the activity of the pathological process, the selectivity of proteinuria, the need for anticoagulant therapy, and the prognosis of the disease.

Topics: Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Kidney Diseases; Kidney Glomerulus

The role of fibrin in the pathogenesis of renal glomerular scarring in the dog was studied. Fibrin deposition, resulting from disseminated intravascular coagulation, was induced by intravenous injection of Liquoid (sodium polyanethol sulphonate). Thirty-eight puppies were killed from 30 minutes to 39 days after treatment, and the renal lesions examined by light, electron and immunofluorescence microscopy. The major acute lesions in the glomeruli were capillary thrombosis, mesangial and endothelial cell swelling and phagocytosis of fibrin, polymorphonuclear leukocyte infiltration and necrosis. Animals that recovered from this acute phase had focal glomerular scars. Affected glomeruli showed combinations of mesangial enlargement, focal tuft hypercellularity, collagen formation, thickening, wrinkling and duplication of the glomerular basement membranes, and some capsular adhesions. These observations indicate that fibrin deposition can be an important mechanism in glomerular scarring in the dog.

Topics: Animals; Benzenesulfonates; Dog Diseases; Dogs; Female; Fibrin; Kidney Diseases; Kidney Glomerulus; Male; Microscopy, Electron; Polyanetholesulfonate

The investigation of fibrinogen degradation products (FDP) in urine has been suggested as a reliable method to detect the glomerular deposition of fibrin. Urinary FDP were investigated in 246 patients with renal disease by means of a latex test in 100 of them (positive in 54%); in the remaining 146 patients the Merskey method was used which gave positive results in 26% of them. A significant correlation between urinary protein excretion and FDP was only observed in those patients examined with the latex test. In patients investigated with the Merskey method, the simultaneous determination of serum FDP showed no correlation between FDP values in serum and urine. In those patients studied by means of renal biopsy, a poor correlation was observed between immunofluorescence and electron microscopic evidence of fibrin deposition and urinary FDP. In conclusion, isolated urinary FDP detection is not an index of pathologic coagulation in the glomeruli.

Topics: Biopsy, Needle; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Humans; Kidney Diseases; Kidney Glomerulus; Methods; Platelet Aggregation

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

Topics: Adolescent; Child; Child, Preschool; Factor VIII; Factor XIII; Female; Fibrin; Fibrinogen; Histocytochemistry; Humans; Kidney Diseases; Kidney Glomerulus; Male

During a period when screening for hepatitis B surface antigen (HBsAg) was performed by immunodiffusion using dextran-containing agarose gel, a diffuse precipitation (DP) zone was observed when citrate plasma samples were reacted with certain serum specimens. The DP reaction was noted with a significantly larger number of sera from patients with renal disorders, hepatitis, or certain other virus infections than with sera from apparently healthy blood donors, indicating that it was associated with some type of pathological condition. Highly purified fibrinogen used as detector reagent instead of plasma was sufficient to elicit a precipitation zone similar to that of the DP reaction. In the presence of coagulation inhibitors such as heparin, hirudin and antithrombin III the DP reaction was inhibited, suggesting that the precipitation zone represents coagulation. Cross-linked fibrin was demonstrated in the precipitates of DP-positive sera but not in the corresponding zone of a DP-negative serum.

Topics: Blood Coagulation; Factor X; Fibrin; Hepatitis; Humans; Immunodiffusion; Kidney Diseases; Thrombin; Thromboplastin

Topics: Basement Membrane; Capillaries; Eclampsia; Endothelium; Epithelium; Female; Fibrin; Foam Cells; Humans; Kidney; Kidney Diseases; Kidney Glomerulus; Lipids; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Thrombosis

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

Topics: Collagen; Connective Tissue; Extracellular Space; Fetus; Fibrin; Fibronectins; Histocytochemistry; Humans; Kidney Diseases; Neoplasms; Reticulin; Tissue Distribution

Topics: Adult; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Kidney Diseases; Methods; Pre-Eclampsia; Pregnancy

Topics: Female; Fibrin; Humans; Japan; Kidney Diseases; Kidney Glomerulus; Male; Middle Aged; Thrombosis

We report on investigations describing the use of a biological adhesive system for tissue adhesion and local haemostasis. This system consists of highly concentrated native fibrinogen and thrombin. Clotting factor XIII is admitted for reinforcement of the fibrin network. In experimental partial kidney resection this system was used with excellent results. This experience led to successful application of this method in 15 patients who underwent partial nephrectomy for various diseases.

Topics: Animals; Fibrin; Fibrinogen; Humans; Kidney; Kidney Diseases; Male; Nephrectomy; Rats; Tissue Adhesives; Wound Healing

Topics: Acute Kidney Injury; Anemia; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Hemostasis; Humans; Kidney Diseases; Kidney Failure, Chronic; Peritoneal Dialysis; Polycythemia; Renal Dialysis

The implantation and one hour post-transplant renal biopsies from three types of allograft recipients were compared with a blind grading system: (1) 25 cadaver kidneys preserved by pulsatile perfusion, (2) seven cadaver kidneys preserved by simple hypothermia following electrolyte solution flush, (3) 18 kidneys from living-related donors. Significant lesions were found only in cadaver kidneys which had received pulsatile preservation. Microscopic findings were correlated with perfusing agent, length of perfusion and its characteristics, and subsequent clinical course of the patient. Perfusion-related injury was found to be morphologically identical to hyperacute rejection, although the lesion is produced by quite different mechanisms. Pulsatile preservation appears to be associated with a spectrum of mechanical endothelial injury ranging from minute breaks visible only ultrastructurally to areas of complete denudation baring the basement membrane. The exposed collagen activates the clotting sequence resulting in platelet and fibrin deposition, whereas in classical hyperacute rejection the triggering mechanism is cytotoxic recipient antibody. The extent of perfusion-related injury correlates well with length of preservation, quantity of fibrin deposited, and, most importantly, with both the immediate and long-term post-transplant failure rate. In some patients the injury appears to be produced by cytotoxic antibodies in the plasma perfusate, which combine with antigens in the kidney ex vivo. The Ag-Ab complex activates complement and coagulation sequences in vivo after reimplantation. Early results with albumin or purified plasma fraction perfusates suggest this portion of perfusion-related injury can be eliminated. Comparison of pre- and postimplantation biopsies of the kidneys preserved by simple hypothermia or by pulsatile preservation suggests that perfusion-related injury is much more common than is true hyperacute rejection mediated by recipient cytotoxic antibodies. We suggest that the term "hyperacute rejection" be reserved for situations where significant endothelial drainage has been excluded by preimplantation biopsy and where recipient cytotoxic antibodies can be proved.

Topics: Cadaver; Fibrin; Fluorescent Antibody Technique; Humans; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Organ Preservation; Perfusion; Postoperative Complications; Tissue Survival; 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

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

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

Topics: Acute Disease; Adolescent; Adult; Aged; Chronic Disease; Female; Fibrin; Humans; Kidney Diseases; Male; Middle Aged; Nephrotic Syndrome

Topics: Adult; Arteries; Biopsy; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Graft Rejection; Humans; Hypertension, Malignant; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Tubular Necrosis, Acute; Pre-Eclampsia; Pregnancy; Scleroderma, Systemic; Transplantation, Homologous; Vascular Diseases

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Fibrin; Humans; Infections; Kidney Diseases; Phospholipids; Shock, Septic

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; 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: Aged; Aorta, Abdominal; Aortic Aneurysm; Autopsy; Blood Vessel Prosthesis; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Kidney; Kidney Diseases; Kidney Glomerulus; Middle Aged; Polytetrafluoroethylene; Postoperative Complications; Rupture, Spontaneous

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

Topics: Adult; Aged; Autoimmune Diseases; Biopsy, Needle; Bronchiectasis; Chronic Disease; Empyema; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Humans; Kidney; Kidney Diseases; Lung; Lung Diseases; Male; Microscopy, Electron; Middle Aged; Phagocytosis; Pleural Diseases; Pneumonia

Topics: Child; Child, Preschool; Female; Fibrin; Fibrinogen; Hematuria; Humans; Infant; Kidney Diseases; Male; Nephritis; Nephrosis; Nephrotic Syndrome; Proteinuria; Purpura; Urinary Tract Infections

Topics: Female; Fibrin; Fibrinogen; Fibrinolysis; Hematuria; Humans; Kidney Diseases; Kidney Pelvis; Male; Prostate; Proteinuria; Ureter; Urethra; Urinary Bladder; Urinary Tract

Topics: Adult; Antibodies; Female; Fibrin; Humans; Kidney Diseases; Methods; Prospective Studies; Recurrence; Urinary Bladder Diseases; Urinary Catheterization; Urinary Tract Infections

The site and extent of intrarenal fibrin deposition has been examined by routine histological staining, immunofluorescence, and electron microscopy in 109 patients with a wide variety of renal diseases. The findings have been correlated with the amount of urinary fibrin/fibrinogen degradation product (FDP) excretion as measured by the tanned red cell haemagglutination inhibition immunoassay. The results show that routine histological stains (Martius Scarlet Blue and Picro Mallory) are unreliable, particularly where there is mesangial accumulation of material or where the amount of fibrin deposited is small and confined to a subendothelial position. Similarly the electron microscope may overassess the degree of fibrin deposition, particularly if this is associated with the deposition of immunoglobulins and complement. There is a close relationship between the site and extent of fibrin, as detected by immunofluorescence, and the maximal urinary FDP excretion.

Topics: Adult; Basement Membrane; Biopsy; Child; Complement System Proteins; Cytoplasm; Endothelium; Erythrocytes; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Hemagglutination Inhibition Tests; Histocytochemistry; Humans; Immunoassay; Immunoglobulins; Kidney; Kidney Diseases; Kidney Glomerulus; Microscopy, Electron

Topics: Adult; Autopsy; Basement Membrane; Biopsy; Biopsy, Needle; Epithelium; Female; Fibrin; Graft Rejection; Humans; Ischemia; Kidney; Kidney Cortex; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Male; Microscopy, Electron; Necrosis; Thrombosis; Transplantation, Homologous

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

Topics: Adult; Aged; Anemia, Hemolytic; Blood Cell Count; Creatinine; Erythrocytes; Female; Fibrin; Fibrinogen; Fluorescein Angiography; Humans; Hypertension; Iodine Isotopes; Kidney Diseases; Male; Middle Aged; Retinal Diseases; Retinal Vessels

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

To examine the possibility that intravascular haemolysis may lead to intravascular coagulation we have compared the degree of fibrin deposition, as measured by levels of serum fibrinogen-fibrin degradation products (F.D.P.), in two different types of intravascular haemolysis associated with red cell fragmentation. F.D.P. levels in 56 patients with intravascular haemolysis secondary to prosthetic heart valves were compared with those in 18 patients who had microangiopathic haemolytic anaemia (M.H.A.) associated with malignant hypertension or renal disease. F.D.P. levels were raised in almost all the patients with M.H.A., and this group had significantly higher levels than any of the valve replacement groups. In contrast, in the prosthetic valve patients F.D.P. levels were usually normal and bore no relation to the degree of haemolysis. It is suggested that in the absence of other precipitating factors intravascular haemolysis will not initiate intravascular coagulation. In M.H.A., while the intravascular haemolysis appears to be a consequence of an underlying intravascular coagulation, it is likely that persistence of the coagulation disturbance is related more to factors such as small vessel damage than to the release of any thromboplastic substances from fragmented red cells.

Topics: Adult; Anemia, Hemolytic; Aortic Valve; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Heart Valve Prosthesis; Humans; Hypertension, Malignant; Kidney Diseases; Male; Middle Aged; Mitral Valve

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: Fibrin; Fibrinogen; Fluorescent Antibody Technique; Histocytochemistry; Humans; Kidney; Kidney Diseases; Methods; Staining and Labeling

Topics: Abortion, Missed; Abruptio Placentae; Blood Coagulation Tests; Collagen Diseases; Erythrocytes; Esters; Female; Fibrin; Fibrinolysis; Fluorides; Hemagglutination Inhibition Tests; Humans; Kidney Diseases; Latex Fixation Tests; Leukemia; Ovarian Neoplasms; Pre-Eclampsia; Pregnancy; Pyruvates; Shock; Staphylococcus; Uterine Neoplasms

This describes the sodium sulphate-Alcian Blue (SAB) method for staining amyloid in paraffin sections. Its value lies in the possibility of subsequent counterstaining and thus of revealing the structural relationships of amyloid. In the kidney the topical disposition of amyloid closely resembles the disposition of fibrin in the kidney of diabetics; this suggests that upset in vascular permeability plays a part in determining the site of the amyloid deposits. Furthermore, an aging process in amyloid can now be envisaged resembling the aging of extraluminal fibrin. Both materials proceed to a hyalin material that, staining like collagen, merits the name pseudo-collagen. This term we apply to a hyalin, staining like collagen, for which, we can postulate a specific precursor.

Topics: Amyloid; Amyloidosis; Collagen; Diabetes Mellitus; Diabetic Angiopathies; Fibrin; Histological Techniques; Humans; Hyalin; Kidney; Kidney Diseases; Microscopy; Staining and Labeling

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

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

Topics: Chronic Disease; Factor XIII Deficiency; Fibrin; Humans; Kidney Diseases

Topics: Animals; Blood Coagulation Tests; Ethanol; Evaluation Studies as Topic; Female; Fibrin; Fibrinogen; Hematologic Diseases; Humans; Kidney Diseases; Liver Diseases; Male; Neoplasms; Peptide Hydrolases; Postoperative Complications; Postpartum Period; Pregnancy; Protamines; Snakes; Thrombin; Venoms

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

Topics: Adolescent; Adult; Angina Pectoris; Chronic Disease; Diabetes Mellitus; Female; Fibrin; Fibrinogen; Hematologic Diseases; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Myocardial Infarction; Neoplasms

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

A rapid slide test for the detection of degradation products of fibrinogen/fibrin (FDP) using a new antibody-coated latex particle is described. The latex particle has been specifically coated with antibody to fragments D and E. The latex agglutination test (Thrombo-Wellcotest) has been compared with the tanned red cell haemagglutination inhibition immunoassay (TRCHII) in 143 patients with a variety of clinical conditions. There is a high degree of agreement between the methods with a coefficient of correlation of 0.83. The method provides a rapid, simple screening test for fibrin degradation products.

Topics: Antibodies; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Humans; Hyperthyroidism; Kidney Diseases; Latex; Liver Diseases; Methods; Microspheres; Neoplasms; Pulmonary Embolism

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: Angiography; Animals; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Embolism, Fat; Escherichia coli Infections; Female; Fibrin; Infarction; Kidney; Kidney Cortex Necrosis; Kidney Diseases; Kidney Glomerulus; Lipids; Rabbits; Shwartzman Phenomenon; Toxemia; Triglycerides

Disseminated intravascular coagulation as indicated by glomerular capillary thrombosis was induced in unprepared virgin rats by the infusion of endotoxin. Dose-time curves revealed that the minimal amount necessary was 0.9 mg and the time required was 3 hours. A marked difference in susceptibility between the summer and winter seasons was observed, the animals being more sensitive in the former. The platelet count decreased in a dose-related manner; however, there was no difference between an infusion and injection regimen. There was no difference in platelet numbers between the animals who had fibrin deposits and those free of fibrin. Plasma hemoglobin increased by 500% in those animals who developed glomerular fibrin deposition and the hematocrit decreased less profoundly. The data demonstrate that unprepared virgin rats can be used as an experimental model for studying glomerular fibrin deposition, the hallmark of what is generally referred to as the generalized Shwartzman reaction, if endotoxin is continuously infused rather than injected.

Topics: Animals; Blood Cell Count; Blood Platelets; Capillaries; Disease Models, Animal; Endotoxins; Escherichia coli; Female; Fibrin; Hematocrit; Hemoglobins; Kidney Diseases; Kidney Glomerulus; Rats; Rats, Inbred Strains; Seasons; Shwartzman Phenomenon; Thrombosis; Time Factors

Topics: Antigens; Fibrin; Fibrinogen; Humans; Immunoassay; Kidney Diseases; Kidney Transplantation; Transplantation, Homologous; Urine; Warfarin

The coagulation and fibrinolytic mechanisms were investigated in a group of patients with severe pre-eclampsia and eclampsia and the findings were compared with those of healthy women in late pregnancy. In patients with pre-eclampsia the following significant differences were found: (1) greater depression of plasma fibrinolytic activity (euglobulin lysis time) than in normal pregnancy, (2) a higher level of inhibitor to urokinaseinduced lysis, (3) increased levels of serum fibrin degradation products, and (4) reduced platelet counts.In patients with eclampsia a progressive increase of the level of serum fibrin degradation products was found over the three days following eclamptic seizures. No such increase occurred after grand mal seizures in late pregnancy. The findings in this study support the view that intravascular clotting is taking place in pre-eclampsia and that this disturbance of the balance between coagulation and fibrinolysis may be localized to certain areas of the vascular compartment, particularly the placental and renal circulations. Fibrin deposition in the maternal vessels supplying the placenta would impair the placental blood flow, which may explain the placental insufficiency which occurs in pre-eclampsia. Likewise fibrin deposition in the renal vasculature will result in glomerular damage and proteinuria. Hypertension may be related to the renal ischaemic changes or a compensatory response to the presence of fibrin deposition in the vascular compartment. This evidence of intravascular fibrin deposition raises the question of the possible therapeutic value of antithrombotic agents to inhibit the clotting process. On a theoretical basis such treatment might be expected to improve blood flow to the placenta and thereby fetal growth.

Topics: Adult; Blood Coagulation; Blood Platelets; Eclampsia; Embryonic and Fetal Development; Epilepsy, Tonic-Clonic; Female; Fibrin; Fibrinolysis; Fibrinolytic Agents; Humans; Hypertension; Ischemia; Kidney; Kidney Diseases; Maternal-Fetal Exchange; Placenta; Pre-Eclampsia; Pregnancy; Proteinuria; Serum Globulins

Topics: Biopsy; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Humans; Immunodiffusion; Kidney; Kidney Diseases; Kidney Function Tests

Topics: Adult; Body Weight; Chyle; Diet Therapy; Female; Fibrin; Fistula; Humans; Kidney Diseases; Lymphatic Diseases; Lymphatic System; Urine; Urography

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

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: Adult; Agglutination Tests; Arthritis, Rheumatoid; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Contraceptives, Oral; Erythrocytes; False Negative Reactions; False Positive Reactions; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Hemagglutination Inhibition Tests; Hodgkin Disease; Humans; Immunoassay; Immunodiffusion; Kidney Diseases; Liver Cirrhosis; Lymphoma, Non-Hodgkin; Male; Methods; Middle Aged; Myocardial Infarction; Neoplasms; Plasminogen; Staphylococcus

Topics: Animals; Antibodies; Fibrin; Fibrinogen; Humans; Immune Sera; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Postoperative Complications; Rats; Transplantation Immunology; Transplantation, Homologous

A single dose of endotoxin given to rats with obstructive jaundice produced death with intravascular coagulation. This action was apparently due to delayed clearance of endotoxin from the circulation. The finding is relevant to "hepatorenal failure," which can be caused by bacteraemia after biliary tract operations.

Topics: Acute Kidney Injury; Animals; Blood Coagulation Tests; Blood Platelets; Cholestasis; Endotoxins; Escherichia coli; Fibrin; Fibrinogen; Kidney Diseases; Liver Diseases; Prothrombin Time; Rats; Thrombelastography; Thrombin

Topics: Animals; Electrophoresis; Fibrin; Humans; Immune Sera; Immunodiffusion; Kidney; Kidney Diseases; Lupus Erythematosus, Systemic; Rabbits; Urine

Topics: Adult; Antigen-Antibody Reactions; Biopsy; Cardiovascular Diseases; Cesarean Section; Female; Fibrin; Humans; Hypertension; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Lysosomes; Obstetric Labor Complications; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pyelonephritis; Serotonin

Topics: Adult; Child; Fibrin; Humans; Infant; Kidney Diseases

Topics: Adolescent; Adult; Anemia, Hemolytic; Beta-Globulins; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Child, Preschool; Complement System Proteins; Female; Fibrin; Fluorescent Antibody Technique; Heparin; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Nephritis; Nephrotic Syndrome; Purpura; Uremia; Urinary Tract Infections

Topics: Animals; Fibrin; Fibrinogen; Kidney Diseases; Rabbits; Rats

Topics: Adolescent; Adult; Female; Fibrin; Fibrinolysis; Fibrinolytic Agents; Histocytochemistry; Humans; Kidney; Kidney Diseases; Macroglobulins; Male; Nephrectomy; Plasminogen; Renal Dialysis; Veins

Topics: Acid Phosphatase; Animals; Choline Deficiency; Diet; Endoplasmic Reticulum; Esterases; Fibrin; Histocytochemistry; Kidney; Kidney Diseases; Kidney Tubules; Lysosomes; Male; Microscopy; Microscopy, Electron; Periodic Acid; Rats; Staining and Labeling

Topics: Adolescent; Adult; Capillaries; Fibrin; Humans; Kidney Diseases; Kidney Glomerulus; Male; Middle Aged

In chronic renal failure and after acute renal failure, fibrinogen levels are raised and there is diminished fibrinolysis as the result of renal damage. A similar situation is found in nephrosis, possibly due to fibrinolytic inhibitors. Increased levels of cryofibrinogen were found in one quarter of cases of acute nephritis, nephrosis, and acute and chronic renal failure. In addition, after acute renal failure low platelet counts, prolonged thrombin times, and high levels of fibrin degradation products, yet with diminished fibrinolysis, indicate that intravascular coagulation has occurred. A positive result for fibrin degradation products was found in 17 of 20 cases of acute renal failure but in none of 10 cases of chronic uraemia. Intravascular coagulation is a process in which fibrin is deposited in the glomerular filters and may account for anuria, and, in the renal vasculature, where it may cause ischaemic tubular necrosis.

Topics: Acute Kidney Injury; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Inhibition Tests; Humans; Immunoelectrophoresis; Kidney Diseases; Kidney Failure, Chronic; Nephritis; Nephrotic Syndrome; Plasminogen; Uremia

Topics: Aneurysm; Animals; Arteritis; Autoimmune Diseases; Blood Proteins; Fibrin; Hybridization, Genetic; Kidney Diseases; Kidney Glomerulus; Mice

Topics: Animals; Autoradiography; Capillaries; Endotoxins; Fibrin; Glycosaminoglycans; Histocytochemistry; Kidney Diseases; Kidney Glomerulus; Rabbits; Research; Salmonella; Shwartzman Phenomenon; Sulfur Isotopes; Thrombosis; Toxicology

Topics: Animals; Catheterization; Fibrin; Injections, Intravenous; Kidney Cortex Necrosis; Kidney Diseases; Mononuclear Phagocyte System; Pathology; Rabbits; Research; Shwartzman Phenomenon; Thorium Dioxide; Toxicology

Topics: Aminocaproates; Aminocaproic Acid; Animals; Arteriosclerosis; Fibrin; Fibrinolysis; Glycosuria; Hematuria; Kidney Diseases; Kidney Glomerulus; Pharmacology; Pulmonary Embolism; Rabbits; Rats; Research; Thrombin

Topics: Brain Diseases; Brain Edema; Fibrin; Kidney Cortex Necrosis; Kidney Diseases; Kidney Glomerulus; Myocardial Infarction; Necrosis; Pathology; Pulmonary Embolism; Shwartzman Phenomenon; Thrombosis

Topics: Deoxyribonuclease I; Dogs; Fibrin; Fibrinolysis; Histocytochemistry; Kidney; Kidney Diseases; Mercury Poisoning; Plasminogen; Research; Streptodornase and Streptokinase; Streptokinase; Toxicology

In the presence of reticuloendothelial blockade, the intravenous injection of a protein antigen into specifically immunized rabbits or the infusion of soluble immune complexes into normal animals has been shown to result in the production of bilateral renal cortical necrosis. The similarity in the pathogenesis of this lesion and that seen in the classical generalized Shwartzman reaction produced by bacterial endotoxins is indicated by (a) the failure of both lesions to develop in animals pretreated with large doses of heparin, (b) by the finding of "heparin-precipitable fibrinogen" in the circulation, and (c) by the presence of massive fibrin deposits within the glomerular capillaries. These findings indicate that antigen-antibody reactions in vivo are capable of activating the blood coagulation system and that the mode of action of bacterial endotoxins may have an immunological basis.

Topics: Animals; Antigen-Antibody Complex; Antigen-Antibody Reactions; Capillaries; Endotoxins; Fibrin; Fibrinogen; Kidney Cortex Necrosis; Kidney Diseases; Kidney Glomerulus; Necrosis; Rabbits; Shwartzman Phenomenon

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

Topics: Aminocaproates; Aminocaproic Acid; Animals; Anticoagulants; Electrons; Fibrin; Kidney Diseases; Kidney Glomerulus; Necrosis; Nephrosclerosis; Pathology; Rabbits; Research; Thrombin; Thromboplastin; Thrombosis

An immunofluorescent study of renal biopsies from patients with toxemia of pregnancy has been performed. It was found that the glomeruli consistently showed bright staining for fibrin within endothelial cells, as well as occasional deposits along the basement membrane. Gamma globulin was only occasionally demonstrable, generally in the form of irregular deposits along the basement membrane. beta(1C) was absent and albumin was not seen in glomeruli, except sometimes in the form of droplets within epithelial cells. In biopsies from pregnant patients without toxemia only equivocal staining for fibrin was seen. On the basis of these observations and other evidence discussed, it is proposed that the accumulation of fibrin in glomeruli reflects a prolonged state of intravascular clotting in toxemia and that the arrest in glomeruli of some form of circulating fibrin constitutes the basic pathogenic mechanism of the glomerular damage in this disease.

Topics: Basement Membrane; Biopsy; Epithelial Cells; Female; Fibrin; Humans; Kidney Diseases; Kidney Glomerulus; Pathology; Pre-Eclampsia; Pregnancy

Topics: Fibrin; Hypersensitivity; Immune System Diseases; Kidney Cortex Necrosis; Kidney Diseases; Muscle, Smooth; Necrosis; Shwartzman Phenomenon