Clinical significance of urinary plasminogen and fibrinogen gamma chain as novel potential diagnostic markers for non-small-cell lung cancer.

BACKGROUND: Urinary proteins could be useful as markers for the detection of non-small-cell lung cancer (NSCLC). We investigated the levels of two different proteins in urine samples from NSCLC patients and assessed their diagnostic value. METHODS: Urinary plasminogen (PLG) and fibrinogen gamma chain (FGG) levels in 112 NSCLC patients and 197 controls were detected using enzyme linked immunosorbent assay (ELISA). The expression of FGG and PLG in 20 NSCLC tissues and paired adjacent non-tumour tissues were detected through immunohistochemistry. The diagnostic value of FGG and PLG for NSCLC was evaluated through a receiver operating characteristic curve (ROC). RESULTS: PLG and FGG were significantly elevated in NSCLC tissues vs paired adjacent non-tumour tissues (p = 0.000) and in urinary samples from NSCLC patients vs healthy controls (p = 0.000). The expression level of PLG in urinary samples was related only to the histological type (p = 0.001). Further, ROC curve analysis revealed that PLG, FGG, and their combination could distinguish NSCLC and its subtypes from healthy controls with an AUC ranging from 0.827 to 0. 947. By comparing urine samples with matching plasma CEA from NSCLC stage I-IV patients (n = 81) and healthy controls (n = 31), the combination of CEA with PLG or FGG showed that the AUC was 0.889 and 0.806, respectively, which is superior to a single biomarker alone. CONCLUSIONS: These two urinary proteins could serve as potential markers for the diagnosis of NSCLC.

Urinary fibrinogen is elevated in hospitalized patients undergoing angiography.

OBJECTIVES: Previously, we found that urinary fibrinogen (Fg) levels were positively related to contrast-induced acute renal injury degree in mice. Reduction of fibrinogen in heterozygous mice can improve renal function. Here, we prospectively observed the variation in urinary Fg levels in patients undergoing angiography to determine the relationship between serum creatinine (Scr) and serum cystatin C (Cys C) levels. METHODS: Serum Cys C and urinary Fg levels were evaluated by ELISA before and 2, 12, and 24 h after angiography in 115 enrolled inpatients. Scr was assessed before and 24 and 48 h after angiography. Data were analyzed using ANOVA or Kruskal-Wallis ANOVA and Spearman correlation. RESULTS: Urinary Fg levels were elevated as early as 2 h after angiography and decreased thereafter before returning to baseline levels 24 h after angiography. Urinary Fg was correlated with the amount of contrast agent ( r = 0.24, p = 0.036) and the presence of diabetes and hypertension ( r = 0.31, r = 0.28, p < 0.05, respectively). Urinary Fg levels 2 h after angiography were positively related with Cys C at 12 and 24 h and Scr at 48 h after angiography ( r = 0.34, r = 0.51, r = 0.85, p < 0.05, respectively). CONCLUSIONS: Our results showed that variations in urinary Fg levels are consistent with serum Cys C and Scr in patients undergoing angiography and that urinary Fg levels were the earliest parameter to become elevated. Urinary Fg should be investigated as a useful predictor for abnormal renal function after angiography.

Fibrinogen links podocyte injury with Toll-like receptor 4 and is associated with disease activity in FSGS patients.

AIM: Fibrinogen (Fg) is reported to participate in inflammation through Toll-like receptor 4 (TLR4). However, it remains unknown whether Fg might induce podocyte damage through TLR4 and be related to disease activity in patients with focal segmental glomerulosclerosis (FSGS). METHODS: We observed Fg-induced alterations in actin and apoptosis in cultured human podocytes transfected with or without TLR4 siRNA. Expression of TLR4, phospho-p38 MAPK and phospho-NF-κB p65 was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blotting, and we analysed urinary Fg levels in adriamycin-treated mice and double immunofluorescence staining for TLR4, Fg and podocin. Urinary Fg changes were also analyzed in FSGS patients under prednisone treatment. RESULTS: First, Fg dose-dependently induced actin damage and apoptosis in cultured human podocytes, with an Fg-induced increase in TLR4 expression, and TLR4 siRNA transfection prevented these effects. TLR4 knockdown inhibited activation of p38 MAPK and NF-κB p65 in podocytes. Elevated urinary Fg levels were positively correlated with albuminuria in adriamycin-treated mice, in which Fg and TLR4 colocalized and exhibited increased expression in podocytes. Additionally, elevated urinary Fg levels were positively correlated with 24-h proteinuria and foot process width in FSGS patients. Urinary Fg levels were significantly decreased in patients with complete remission but not in those without remission. CONCLUSIONS: Fg induced podocytes injury via the TLR4-p38 MAPK-NF-κB p65 pathway. In FSGS patients, urinary Fg levels reflect therapeutic response to prednisone and disease activity.

Successful Treatment of Generalized Essential Telangiectasia With 6-Mercaptopurine.

Generalized essential telangiectasia (GET) is a notoriously difficult to treat disorder with no current satisfactory treatments. This case and discussion report the use of 6-mercaptopurine (6-MP) as a successful treatment for GET. Moreover, we show that GET may represent a state of increased angiogenesis, a paradigm shift from the current understanding that these telangiectasias represent dilatations of only pre-existing vessels. This new view of GET may drive others to look at novel agents for treatment.

J Drugs Dermatol. 2017;16(3):280-282.

Novel urinary biomarkers and their association with urinary heavy metals in chronic kidney disease of unknown aetiology in Sri Lanka: a pilot study

Introduction: Chronic kidney disease of unknown etiology (CKDu) has emerged as a significant public health problem in Sri Lanka. The role of environmental exposure to cadmium and arsenic in the aetiology of CKDu is still unclear. Identification of a panel of novel urinary biomarkers would be invaluable in the study of toxin mediated damage postulated to be the aetiology of CKDu. Objectives: The aims of this study were to evaluate the profile of novel urinary biomarkers in CKDu patients and identify any association with environmental exposure to heavy metals. Methods: Thirty seven randomly selected CKDu patients attending a renal clinic in the North Central Province and two control groups namely a farmer group (n=39) and a non-farmer group (n=40) from a non-endemic area were included in this comparative cross sectional study. Urine samples were analyzed for heavy metals and five urinary biomarkers. Results: CKDu patients had significantly elevated urinary levels of fibrinogen (198.2 ng/mg creatinine p<0.001), clusterin (3479 ng/mg creatinine p<0.001), cystatin-C (5124.8 ng/mg creatinine p<0.001) and ß2-microglobulin (9913.4 ng/mg creatinine p<0.001) compared to the control groups. Fibrinogen and ß2-microglobulin were the best to discriminate CKDu patients from normal individuals with the receiver operator areas under the curve being 0.867 and 0.853, respectively. Urinary fibrinogen and KIM-1 levels correlated positively with urinary arsenic levels. KIM-1 levels correlated positively with urinary mercury and lead levels but no correlation was seen with urinary cadmium levels. Conclusions: Fibrinogen and ß2-microglobulin have the potential of being a screening tool for detection of CKDu and may aid the early diagnosis of toxin mediated tubular injury in CKDu. Their usefulness need to be further validated in a larger epidemiological study of patients with early stages of CKDu.

Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study.

OBJECTIVE: The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). METHODS: In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. RESULTS: 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. CONCLUSIONS: In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153).

Identification of urinary peptide biomarkers associated with rheumatoid arthritis.

Early diagnosis and treatment of rheumatoid arthritis are associated with improved outcomes but current diagnostic tools such as rheumatoid factor or anti-citrullinated protein antibodies have shown limited sensitivity. In this pilot study we set out to establish a panel of urinary biomarkers associated with rheumatoid arthritis using capillary electrophoresis coupled to mass spectrometry. We compared the urinary proteome of 33 participants of the Scottish Early Rheumatoid Arthritis inception cohort study with 30 healthy controls and identified 292 potential rheumatoid arthritis-specific peptides. Amongst them, 39 were used to create a classifier model using support vector machine algorithms. Specific peptidic fragments were differentially excreted between groups; fragments of protein S100-A9 and gelsolin were less abundant in rheumatoid arthritis while fragments of uromodulin, complement C3 and fibrinogen were all increasingly excreted. The model generated was subsequently tested in an independent test-set of 31 samples. The classifier demonstrated a sensitivity of 88% and a specificity of 93% in diagnosing the condition, with an area under the receiver operating characteristic curve of 0.93 (p<0.0001). These preliminary results suggest that urinary biomarkers could be useful in the early diagnosis of rheumatoid arthritis. Further studies are currently being undertaken in larger cohorts of patients with rheumatoid arthritis and other athridities to assess the potential of the urinary peptide based classifier in the early detection of rheumatoid arthritis.

Pharmacological and genetic depletion of fibrinogen protects from kidney fibrosis.

Fibrinogen (Fg) has been implicated in the pathogenesis of several fibrotic disorders by acting as a profibrotic ligand for a variety of cellular surface receptors and by modulating the provisional fibrin matrix formed after injury. We demonstrated increased renal Fg expression after unilateral ureteral obstruction and folic acid (FA) nephropathy in mice, respectively. Urinary Fg excretion was also increased in FA nephropathy. Using in vitro and in vivo approaches, our results suggested that IL-6 mediates STAT3 activation in kidney fibrosis and that phosphorylated (p)STAT3 binds to Fgα, Fgß, and Fgγ promoters in the kidney to regulate their transcription. Genetically modified Fg heterozygous mice (∼75% of normal plasma Fg levels) exhibited only 3% kidney interstitial fibrosis and tubular atrophy after FA nephropathy compared with 24% for wild-type mice. Fibrinogenolysis through Ancrod administration after FA reduced interstitial fibrosis more than threefold compared with vehicle-treated control mice. Mechanistically, we show that Fg acts synergistically with transforming growth factor (TGF)-ß1 to induce fibroblast proliferation and activates TGF-ß1/pSMAD2 signaling. This study offers increased understanding of Fg expression and molecular interactions with TGF-ß1 in the progression to kidney fibrosis and, importantly, indicates that fibrinogenolytics like Ancrod present a treatment opportunity for a yet intractable disease.

Urine protein biomarkers for the diagnosis and prognosis of necrotizing enterocolitis in infants.

OBJECTIVES: To test the hypothesis that an exploratory proteomics analysis of urine proteins with subsequent development of validated urine biomarker panels would produce molecular classifiers for both the diagnosis and prognosis of infants with necrotizing enterocolitis (NEC). STUDY DESIGN: Urine samples were collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time of initial clinical concern for disease. The urine from 59 infants was used for candidate biomarker discovery by liquid chromatography/mass spectrometry. The remaining 60 samples were subject to enzyme-linked immunosorbent assay for quantitative biomarker validation. RESULTS: A panel of 7 biomarkers (alpha-2-macroglobulin-like protein 1, cluster of differentiation protein 14, cystatin 3, fibrinogen alpha chain, pigment epithelium-derived factor, retinol binding protein 4, and vasolin) was identified by liquid chromatography/mass spectrometry and subsequently validated by enzyme-linked immunosorbent assay. These proteins were consistently found to be either up- or down-regulated depending on the presence, absence, or severity of disease. Biomarker panel validation resulted in a receiver-operator characteristic area under the curve of 98.2% for NEC vs sepsis and an area under the curve of 98.4% for medical NEC vs surgical NEC. CONCLUSIONS: We identified 7 urine proteins capable of providing highly accurate diagnostic and prognostic information for infants with suspected NEC. This work represents a novel approach to improving the efficiency with which we diagnose early NEC and identify those at risk for developing severe, or surgical, disease.

A novel urine peptide biomarker-based algorithm for the prognosis of necrotising enterocolitis in human infants.

OBJECTIVE: Necrotising enterocolitis (NEC) is a major source of neonatal morbidity and mortality. The management of infants with NEC is currently complicated by our inability to accurately identify those at risk for progression of disease prior to the development of irreversible intestinal necrosis. We hypothesised that integrated analysis of clinical parameters in combination with urine peptide biomarkers would lead to improved prognostic accuracy in the NEC population. DESIGN: Infants under suspicion of having NEC (n=550) were prospectively enrolled from a consortium consisting of eight university-based paediatric teaching hospitals. Twenty-seven clinical parameters were used to construct a multivariate predictor of NEC progression. Liquid chromatography/mass spectrometry was used to profile the urine peptidomes from a subset of this population (n=65) to discover novel biomarkers of NEC progression. An ensemble model for the prediction of disease progression was then created using clinical and biomarker data. RESULTS: The use of clinical parameters alone resulted in a receiver-operator characteristic curve with an area under the curve of 0.817 and left 40.1% of all patients in an 'indeterminate' risk group. Three validated urine peptide biomarkers (fibrinogen peptides: FGA1826, FGA1883 and FGA2659) produced a receiver-operator characteristic area under the curve of 0.856. The integration of clinical parameters with urine biomarkers in an ensemble model resulted in the correct prediction of NEC outcomes in all cases tested. CONCLUSIONS: Ensemble modelling combining clinical parameters with biomarker analysis dramatically improves our ability to identify the population at risk for developing progressive NEC.

Fibrinogen excretion in the urine and immunoreactivity in the kidney serves as a translational biomarker for acute kidney injury.

Fibrinogen (Fg) is significantly up-regulated in the kidney after acute kidney injury (AKI). We evaluated the performance of Fg as a biomarker for early detection of AKI. In rats and mice with kidney tubular damage induced by ischemia/reperfusion (I/R) or cisplatin administration, respectively; kidney tissue and urinary Fg increased significantly and correlated with histopathological injury, urinary kidney injury molecule-1 (KIM-1) and N-acetyl glucosaminidase (NAG) corresponding to the progression and regression of injury temporally. In a longitudinal follow-up of 31 patients who underwent surgical repair of abdominal aortic aneurysm, urinary Fg increased earlier than SCr in patients who developed postoperative AKI (AUC-ROC = 0.72). Furthermore, in a cohort of patients with biopsy-proven AKI (n = 53), Fg immunoreactivity in the tubules and interstitium increased remarkably and was able to distinguish patients with AKI from those without AKI (n = 59). These results suggest that immunoreactivity of Fg in the kidney, as well as urinary excretion of Fg, serves as a sensitive and early diagnostic translational biomarker for detection of AKI.

Fibrinogen alpha chain O-glycopeptides as possible markers of urinary tract infection.

Urinary tract infection (UTI) is the most common bacterial infection leading to substantial morbidity and considerable health care expenditures across all ages. Here we present an exploratory UPLC-MS study of human urine in the context of febrile, complicated urinary tract infection aimed to reveal and identify possible markers of a host response on infection. A UPLC-MS based workflow, taking advantage of Ultra High Resolution (UHR) Qq-ToF-MS, and multivariate data handling were applied to a carefully selected group of 39 subjects with culture-confirmed febrile Escherichia coli UTI. Using a combination of unsupervised and supervised multivariate modeling we have pinpointed a number of peptides specific for UTI. An unequivocal structural identification of these peptides, as O-glycosylated fragments of the human fibrinogen alpha 1 chain, required MS2 and MS3 experiments on two different MS platforms: ESI-UHR-Qq-ToF and ESI-ion trap, a blast search and, finally, confirmation was achieved by matching experimental tandem mass spectra with those of custom synthesized candidate-peptides. In conclusion, exploiting non-targeted UPLC-MS based approach for the investigation of UTI related changes in urine, we have identified and structurally characterized unique O-glycopeptides, which are, to our knowledge, the first demonstration of O-glycosylation of human fibrinogen alpha 1-chain.

Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer.

Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (p<0.05) in bladder cancer samples compared with control urine samples. The increased abundance found in urine from bladder cancer patients compared with controls was confirmed with Western blot for four selected proteins; fibrinogen ß chain precursor, apolipoprotein E, α-1-antitrypsin, and leucine-rich α-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen ß chain and α-1-antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66-85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors.

Urinary excretion of twenty peptides forms an early and accurate diagnostic pattern of acute kidney injury.

Early and accurate detection of acute kidney injury (AKI) is needed to prevent the progression to chronic kidney disease and to improve outcome. Here we used capillary electrophoresis-mass spectrometry to identify urinary peptides predictive of AKI in a training set of 87 urine samples longitudinally collected from patients in an intensive care unit. Within this patient cohort, 16 developed AKI while 14 maintained normal renal function. The sequence of twenty peptides significantly associated with AKI was identified. They were found to be degradation products of six proteins. These formed a diagnostic pattern. Peptides of albumin, α-1-antitrypsin, and ß-2-microglobulin were upregulated but fragments of fibrinogen α and collagens 1 α(I) and 1 α(III) were downregulated in AKI. After cross-validation of the training set, a good diagnostic performance of the marker pattern was found with an area under the ROC curve of 0.91. This was confirmed in a blinded validation set of 20 patients in the intensive care unit and 31 allogeneic hematopoietic stem cell transplantation patients, of which 13 had and 18 had not experienced an episode of AKI. In comparison to more established markers of AKI such as serum cystatin C and urinary kidney injury molecule-1, interleukin-18, and neutrophil gelatinase associated-lipocalin, the proteomic marker pattern was found to be of superior prognostic value, detecting AKI up to 5 days in advance of the rise in serum creatinine.

Coagulation and inflammation in overt diabetic nephropathy: association with hyperhomocysteinemia.

BACKGROUND: Diabetic nephropathy, especially when advanced, is associated with high prevalence of atherosclerotic cardiovascular disease in which inflammation and coagulation may play pathogenic roles. We investigated the relationships between diabetic nephropathy and coagulation, fibrinolysis, or inflammation in patients with Type 2 diabetes. METHODS: We evaluated markers of inflammation and coagulation in 105 Type 2 diabetic patients with various grades of nephropathy and 49 healthy control subjects, in association with plasma total homocysteine (tHcy) measurements. RESULTS: Plasma tHcy concentrations were significantly higher in diabetic patients than in controls (8.96 +/- 3.04 vs. 6.92 +/- 1.36 micromol/l, P < 0.0001). Plasma concentrations of interleukin (IL)-6 were significantly higher in diabetic patients than in control subjects (P < 0.0001). In diabetic patients, plasma tHcy correlated positively with urinary albumin, fibrinogen, IL-6 and plasmin-alpha2-antiplasmin complex (PAP), while plasma tHcy correlated negatively with creatinine clearance (Ccr) and protein C activity. After adjustment for Ccr, IL-6 and protein C activity were significantly associated with plasma tHcy. Plasma tHcy concentrations were significantly higher in patients with overt albuminuria than in those with normoalbuminuria or microalbuminuria, as were plasma concentrations of fibrinogen, prothrombin F1+2, and interleukin-6. CONCLUSIONS: Diabetic nephropathy is associated with elevated markers for both coagulation and inflammation. High plasma homocysteine may be a link between diabetic nephropathy and both chronic inflammation and hypercoagulability, increasing cardiovascular risk.

Specific identification of urinary fibrinogen, fibrinogen degradation products, and cross-linked fibrin degradation products in renal diseases and after renal allotransplantation.

We have applied a sensitive and discriminating electrophoretic technique that distinguishes between fibrinogen, fibrin polymers, fibrinogen degradation products (FDP), and cross-linked fibrin degradation products (XLDP) to evaluate urinary fibrinogen antigen in control subjects and in patients with a variety of renal diseases and after renal allograft transplantation. Although only one of 11 controls showed the trace presence of urinary fibrinogen, 14 of 28 patients with renal disease had urinary fibrinogen antigen, mostly as fibrinogen or fibrin monomer. Thrombin treatment failed to remove fibrinogen from urine, indicating that methods using this step to eliminate clottable protein will overestimate the quantity of urinary fibrinogen and fibrin degradation products. No association was found between the amount or type of antigen and the specific clinical diagnosis or the presence of proteinuria or hematuria, although urinary FDP and XLDP were found only with greater degrees of renal impairment. Fifteen patients were evaluated for 3 weeks after renal transplantation surgery by serial urine and serum electrophoretic analysis. Urinary FDP and XLDP were found significantly more often in the first week after surgery and in association with episodes of acute renal transplant rejection (ARTR) than at other times. This suggests that fibrin deposition and degradation is involved in the pathologic process of ARTR and that identification of specific XLDP and FDP could have diagnostic and prognostic application in such patients.

A diagnostic-prognostic test for bladder cancer using a monoclonal antibody-based enzyme-linked immunoassay for detection of urinary fibrin(ogen) degradation products.

An enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody was developed to determine the clinical value of urinary fibrinogen/fibrin degradation product levels for the identification and management of patients with bladder cancer. Assays were performed on 286 serial urine specimens from 56 bladder carcinoma patients. Specimens were grouped according to whether the patient had an evident tumor at the time of specimen collection (134 specimens, 41 patients) or was clinically disease-free following treatment (152 specimens, 38 patients). Many patients contributed specimens to both groups as determined by their clinical status at the time of collection. In addition, 45 specimens from 33 patients with inflammation of the urogenital tract and 81 specimens from 19 patients with renal or prostatic cancer were assayed for urinary fibrin degradation products. The ELISA, using a high-sensitivity procedure, identified 83% of the specimens from bladder cancer-positive patients with an overall accuracy with all specimens of 78% and a false-negative rate of 5% for all specimens tested. The high-sensitivity ELISA appeared most appropriate for monitoring bladder cancer patients for recurrence of tumor after surgery. The ELISA using a high-specificity procedure appeared most appropriate for screening. The high-specificity ELISA accurately identified 96% of urine specimens from non-bladder cancer patients with a false-positive rate of only 5%. These results demonstrate that the ELISA is an efficient, reliable, quantitative, and noninvasive immunoassay that can be useful both for the identification of bladder cancer patients and for monitoring the course of the disease.

Clinical significance of urinary fibrinogen degradation products in renal disease: study with two methods and correlation with histological findings of intraglomerular coagulation.

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.