Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis.

OBJECTIVE: This study evaluates the utility of urinary pro-thrombotic molecules such as tissue factor (TF), anti-thrombotic molecules such as tissue factor pathway inhibitor (TFPI), and fibrinolytic molecules such as plasmin and d-dimer as biomarkers of lupus nephritis (LN). METHODS: Urine samples from 113 biopsy-proven LN patients (89 active LN and 24 inactive LN), 45 chronic kidney disease patients, and 41 healthy controls were examined for d-dimer, plasmin, TF, and TFPI levels by ELISA. The area under the receiver operating characteristic curve (AUC) analysis, multivariate regression analysis, and Bayesian network analysis were performed to assess the diagnostic value of the assayed molecules in LN. RESULTS: Although urinary d-dimer, plasmin, TF, and TFPI were all elevated in active LN compared to all control groups, and correlated with rSLEDAI and SLICC RAS disease activity indices, urine plasmin emerged as the strongest independent predictor of eGFR and renal disease status, by multivariate regression analysis and Bayesian network analysis. Whereas urine plasmin discriminated active LN from inactive disease with an AUC of 0.84, the combination of urine plasmin and TFPI discriminated ALN from ILN with an AUC of 0.86, with both surpassing the specificity and positive predictive value of traditional markers such as anti-dsDNA and complement C3. CONCLUSION: Both thrombogenic and thrombolytic cascades appear to be upregulated in lupus nephritis, with proteins from both cascades appearing in the urine. Of the coagulation cascade proteins surveyed, urine plasmin emerges as the strongest predictor of eGFR and clinical renal disease in patients with LN.

Urinary fibrin/fibrinogen degradation products measured using an anti-fibrinogen antibody predict orthostatic proteinuria.

BACKGROUND: The aim of this study was to assess the diagnostic value of urinary fibrin/fibrinogen degradation products (uFDP) measured using an anti-fibrinogen antibody in patients with orthostatic proteinuria (OP), and their use in differentiating between OP and glomerulonephritis (GN). METHODS: uFDP were measured using first urine in the morning (supine) and non-first urine during a hospital visit (upright) and then normalized to urine creatinine (uFDP/Cr, ng/mgCr). We compared (i) OP patients (n = 16); (ii) those in remission from nephrotic syndrome (NS, n = 14) and from GN (IgA nephropathy [IgAN], n = 14; Henoch-Schönlein purpura nephritis [HSPN], n = 12); and (iii) those with active GN (IgAN, n = 12; HSPN, n = 19). RESULTS: The uFDP/Cr ratio increased from supine to upright urine in patients with OP (P < 0.001), but decreased in one case. uFDP were excreted in supine urine in 94% of OP patients, with no excretion in NS remission patients or in 92% of GN remission patients (P < 0.001 for both). uFDP/Cr in supine urine was similar between the OP and active GN patients (P = 0.40), whereas proteinuria in supine urine was in the normal range in all OP patients, but was significantly higher in upright urine in the OP patients (P < 0.001). In upright urine, urinary protein/creatinine ratio was significantly lower in patients with OP than in those with active GN (P = 0.005). A uFDP/Cr ratio cut-off of 1,108 ng/mgCr in upright urine correctly differentiated OP from active GN, with a sensitivity of 87.5% and a specificity of 100%. CONCLUSION: Comparison of uFDP levels in supine/upright urine can be reliable for diagnosing OP and for differentiating it from active GN.

Thrombin Generation in Patients With Suspected Venous Thromboembolism.

Increasing number of patients with clinically suspected venous thromboembolism is referred to radiological departments for definitive diagnosis. A simple assay to exclude the diagnosis and avoid radiological examinations is needed. We have reported correlations between D-dimer and prothrombin fragment 1 + 2 measured in plasma and urine. To further develop an analysis based on urine, more understanding of thrombin generation in these patients is needed. The aim of this study was to compare ex vivo thrombin generation with in vivo markers in plasma and urine in patients with and without venous thromboembolism. Urine and blood samples were collected from patients with suspected venous thromboembolism. Commercially available enzyme-linked immunosorbent assay (ELISA) kits were used to analyze the samples for in vivo thrombin generation. The ex vivo thrombogram parameters were measured by the calibrated automated thrombogram assay. Venous thromboembolism was verified with compression ultrasound of the lower extremity deep veins or with computer tomography of the pulmonary arteries. Venous thromboembolism was diagnosed in 117 of 591 patients, and they had significantly higher levels of urine and plasma prothromin fragment 1 + 2, D-dimer, lag time, time to peak, and endogenous thrombin potential when adjusted for covariates. The pattern of ex vivo and in vivo thrombin generation in patients with suspected venous thromboembolism was comparable when adjusted for covariates. Prothrombin fragment 1 + 2 in plasma and urine reflects thrombin generation ex vivo in the same manner. This indicates that urine may be an alternative substrate to quantify a procoagulant state.

Urinary prothrombin fragment 1+2 in patients with venous thrombosis and myocardial infarction.

Patients with venous-thromboembolism (VTE) and myocardial infarction (MI) have elevated prothrombin fragment 1+2 (F1+2) levels. In patients with postoperative VTE, urinary F1+2 (uF1+2) was higher than in individuals without VTE. To explore the relationship between plasma and uF1+2 we performed a pilot study in patients with thrombotic events and healthy controls. In 40 patients with VTE or MI, and 25 age- and sex-matched healthy controls, F1+2 and D-dimer levels were measured in urine and plasma within 48 h after diagnosis. In addition, in all subjects renal function was assessed. Plasma and uF1+2 levels were positively correlated. Compared to controls, patients with VTE had higher levels of both plasma F1+2 (271 vs 160 pmol L(-1), p < 0.05) and uF1+2 levels (38 vs 28 pmol L(-1)), the latter, however, was not statistically significant. Patients with acute MI had similar F1+2 levels as controls in both plasma and urine. Differences in urinary F1+2 levels could not be attributed to differences in concentrations of creatinine or albumin in spot urine samples. Overall, D-dimer and F1+2 levels in urine were extremely low in all groups.

Diagnostic values of urine CYFRA21-1, NMP22, UBC, and FDP for the detection of bladder cancer.

BACKGROUND: We compared the diagnostic utilities of CYFRA 21-1, nuclear matrix protein-22 (NMP22), urinary bladder cancer antigen (UBC), and fibrin/fibrinogen degradation products (FDP) for detecting urinary bladder cancer. METHODS: We assayed CYFRA 21-1, NMP22, UBC and FDP from urine samples for 250 subjects. Among them, 54 were diagnosed as bladder cancer, and the remaining 196, which consisted of healthy individuals and patients with hematuria, inflammation/infection, or benign prostate hyperplasia, were assigned to the control group. RESULTS: Urinary levels of all 4 markers were higher in the bladder cancer group than the control group. The areas under the receiver operating characteristic curves (ROC-AUCs) of CYFRA 21-1, NMP22, UBC and FDP, corrected with urine creatinine concentrations, were 0.90, 0.89, 0.80 and 0.77, respectively, for discriminating bladder cancer from controls. The ROC-AUCs for the combinations of the markers were not significantly higher than those with CYFRA 21-1 or NMP22. NMP22 was the only independent variable for predicting bladder cancer among the four markers in the multivariate analysis. CONCLUSIONS: All 4 tumor biomarkers exhibited diagnostic utility for predicting bladder cancer. Among them, CYFRA 21-1 and NMP22 were the most effective at predicting bladder cancer.

[Clinical implication of urine test for markers of endothelial dysfunction and angiogenesis factors in assessment of tubulointerstitial fibrosis in chronic glomerulonephritis].

AIM: To evaluate contribution of endothelial dysfunction and impairment of endothelial proliferation/ regeneration to mechanisms of development of tubulointerstitial fibrosis (TIF) in chronic glomerulonephritis (CGN) basing on urinary levels of markers of endothelial activation/impairment and angiogenesis factors. MATERIAL AND METHODS: A total of 67 CGN patients entered the study: 19 patients with moderate urinary syndrome (group 1), 37 patients with nephrotic syndrome (group 2), 11 patients with nephrotic syndrome and persistent renal failure (RF). A control group consisted of 12 healthy subjects. The examination covered excretion with urine of Willebrand factor (WF), plasminogen activator inhibitor I (PAL-I), fibrin degradation products (FDP), vascular endothelial growth factor (VEGF). These values were compared with severity of fibrous changes in renal interstitium estimated by biopsy morphometry. RESULTS: CGN patients had signs of affection of parietal effects of vascular endothelium. In particular, increased excretion of functionally active WF, PAI-I and FDP correlating with activity/severity of CGN. The changes were especially noticeable in patients with progressive forms of CGN (with NS and RF). Patients with morphologically verified TIF (interstitial area more than 20%) excretion of endothelial dysfunction markers was higher than in CGN patients free of TIF In a progressive course of nephritis endothelial dysfunction deteriorates by endothelial proliferation/regeneration impairment as shown by reduced urinary excretion of angiogenic factor VEGF and parallel elevation of functionally active WF in urine of patients with severe forms of CGN. Combined contribution of endothelial dysfunction and angiogenesis impairment to mechanisms of TIF development is seen from these values relations with severity of creatinemia and fibrous alterations in tubulointerstitial tissues of the kidney. CONCLUSION: The results point to participation of endothelium in mechanisms promoting development of TIF and RF in CGN both in terms of endothelial dysfunction and impairment of endothelial repair capacity. Clinicomorphological comparisons confirm the significance of WF, PAI-I and VEGF in assessment of local-renal endothelial changes and severity of fibrosis in renal tissue in CGN. Due to availability of the study material, perspectives of fibrogenesis monitoring in the kidneys with the tests appear which is essential for making prognosis and treatment policy in CGN patients.

[Tumor markers of urinary tract carcinoma].

The tumor markers for malignant tumors arisen from urinary system including prostate cancer were reviewed. As for renal cell carcinoma there was no good marker used in routine test level at present. In the diagnosis of urothelial (transitional cell) carcinoma, mainly bladder cancer, 3 methods (urinary BTA, NMP22 and BFP) are used now in Japan. They all seem to be not fully sufficient in respect of the specificity. In foreign countries, new tests such as urinary telomerase and BLCA-4 are used and have been evaluated. On the diagnosis of prostate cancer, serum total PSA is well established and used. Various PSA relation markers have been advocated for the differentiation between benign prostate hypertrophy and carcinoma in so called "gray zone" level of total PSA. In methods based on the molecular forms of PSA, the ratio of free PSA to total PSA (f/T) is widely use, and proPSA is a test that is expected. Other approaches such as volume of index PSA, age specific PSA reference range and PSA velocity are also in practical application. Human glandular kallikrein 2, which belong to the human kallikrein family as well as PSA, is expected as a tumor specific marker.

Tumor markers in the diagnosis of primary bladder cancer. A systematic review.

PURPOSE: We systematically reviewed the available evidence, and obtained and compared summary estimates of the sensitivity and specificity of cytology and the urine based markers bladder tumor antigen, BTA stat (Polymedco, Redmond, Washington), BTA TRAK (Polymedco), NMP22 (Matritech, Cambridge, Massachusetts), telomerase and fibrin degradation product in detecting primary bladder cancer. MATERIALS AND METHODS: Studies on the diagnosis of primary bladder cancer published from 1990 through November 2001 in English and German were retrieved from MEDLINE and EMBASE data bases. In our research we included studies that evaluated 1 or more of the markers, used cystoscopy as the reference standard and allowed the construction of a 2 x 2 contingency table for a per patient analysis. The data plus items on study and clinical characteristics were extracted by 2 observers. Sensitivity and specificity for each marker were estimated using a bivariate random effect meta-analysis. A multivariable analysis was performed to explain study variation. RESULTS: A total of 42 studies were included in our review. Only 2 studies were available on fibrin degradation product, hence a meta-analysis was not possible. Cytology had the best specificity at 94% (95% CI: 90% to 96%). This figure was significantly better than that of the other markers except for telomerase (specificity 86% [71% to 94%]). Telomerase had the best sensitivity (75% [71% to 79%]) but it was not significantly better than that of BTA stat (70% [66% to 74%]). Case control designs yielded lower values for sensitivity for the tumor markers cytology, bladder tumor antigen and BTA stat. CONCLUSIONS: Cytology has the best specificity and telomerase the best sensitivity. However, none of the markers studied here is sensitive enough to be recommended for daily routine.

Bladder cancer. II. Molecular aspects and diagnosis.

The current system used to classify bladder carcinoma by stage and histological grade is very useful, yet still has limited ability to predict the natural history, or treated natural history, of a bladder tumor. Cystoscopy and urine cytology are currently the gold standard in the diagnosis and follow-up of bladder cancer. Classical urine cytology, however, at least in the diagnosis of G1 tumors, is definitely characterized by a relative low sensitivity. The low sensitivity and subjective interpretation of cytology led to the development of several tests to detect bladder cancer in urine. We provide a current, comprehensive review of the literature on bladder tumor markers and summarize their diagnostic potential. In conclusion, under the premise that cystoscopy has never been subjected to evaluation, no diagnostic marker with a sensitivity and specificity comparable to cystoscopy currently exists. The combined analysis of several tumor markers, as in the Immunocyt test, seems to be the most promising approach. In the future, rather highly sensitive tests may be able to replace cystoscopy or prolong the intervals of cystoscopies in the follow-up of selected patients.

Assessment of fibrin-fibrinogen degradation products (Accu-Dx) test in bladder cancer patients.

OBJECTIVES: Measurement of urine fibrin-fibrinogen degradation products has been reported to be a useful marker for bladder malignancies. This is a simple, noninvasive and rapid method in the diagnosis and follow-up of bladder cancer. We performed a prospective study to evaluate the reliability of the Accu-Dx test which detects urinary fibrin and fibrinogen products associated with bladder cancer. MATERIAL AND METHODS: 97 patients were included in this study. 55 patients with bladder cancer were under surveillance, and 35 were evaluated as primary cases. The Accu-Dx test was performed in 7 additional patients presenting with hematuria due to benign disorders. Urine cytology specimens were collected in all, whereas bladder pathology specimens were obtained in 93. The Accu-Dx test was evaluated with regard to the results of urine cytology and pathological assessment, which constituted the gold standard. RESULTS: According to pathology, 69 patients had carcinoma of the bladder. In 48 (69.6%), the Accu-Dx test was positive whereas urine cytology was positive in only 31 (44.9%; p<0.001). Specificity rates were 67.9 and 96.4%, respectively. With higher stages and higher tumor grades, the Accu-Dx test yielded higher positive rates (50% in Ta versus 100% in T2 or higher and 42.9% in G1 versus 94.1% in G3). On the other hand, the test was positive in 6 patients with cystitis of various etiologies. The overall accuracy rate for Accu-Dx was 69%. CONCLUSIONS: The Accu-Dx test is a simple, rapid, reproducible and more importantly a noninvasive method in the detection of bladder malignancies. But it seems inadequate to replace conventional cystoscopy plus pathologic assessment due to its relatively low accuracy and specificity rates. It may be helpful in selecting patients who should be evaluated with rigid endoscopes together with bladder biopsies.

[The usefulness of urinary FDP in the diagnosis of bladder cancer: comparison with NMP22, BTA and cytology].

PURPOSE: We assessed the utility of urine fibrin/fibrinogen degradation products (FDP) as the screening test for bladder cancer. MATERIALS AND METHODS: Single voided specimens were obtained from 87 consecutive patients (61 men and 26 women, mean age 70.7) on cystoscopy, and FDP, NMP22, BTA and cytology test were performed for the same specimens. Final diagnosis of bladder cancer was made by histological examination, which were compared with the results of above four screening methods. RESULTS: Histologically confirmed bladder cancer was found in 14 cases. Overall sensitivity of urinary FDP, NMP22, BTA and cytology were 79, 64, 36 and 36%, respectively. While the sensitivity of FDP was significantly higher than that of BTA and cytology, no significant difference was found between FDP and NMP22. Overall specificity of these four methods were 69, 78, 92 and 90%, respectively. The specificity of FDP and NMP22 were significantly lower than that of BTA and cytology, but satisfactory as a screening test. The sensitivity of the four methods for low-grade and non-invasive tumors were 70, 50, 30 and 10% (G1 or G2, n = 10), and 75, 58, 33 and 25% (Ta or T1, n = 12), respectively. FDP might have a high sensitivity for even low-grade and non-invasive tumors. CONCLUSIONS: FDP in voided urine is a good screening method for bladder cancer because of its high sensitivity for low-grade and non-invasive tumors, and its diagnostic ability could be superior to NMP22.

Urine based markers of urological malignancy.

PURPOSE: A number of urine based markers have been and are being investigated for the diagnosis and prognostication of urological conditions. A majority of these markers have been evaluated in urological neoplasms, particularly bladder cancer. The diagnosis of bladder cancer currently relies on identifying malignant cells in the urine and subsequently visualizing the tumor on cystoscopy. This diagnosis is further confirmed by transurethral resection or biopsy. While urine cytology is specific, it is not sensitive, especially for detecting low grade disease. This characteristic has prompted the search for more accurate markers of bladder cancer. In this review we critically examine the results of studies evaluating various markers for bladder cancer. MATERIALS AND METHODS: The published literature on urine based markers for all urological diseases, particularly bladder cancer, was identified using a MEDLINE search and critically analyzed. The sensitivity, specificity, positive and negative predictive values of the various markers were compared. The benefit of using combined markers rather than a single marker was also analyzed from published reports. RESULTS: Most published literature on urine based markers for urological malignancies involve such markers for diagnosing and prognosticating bladder cancer. Hence, we focused mainly on urine based markers in bladder cancer. Most markers appear to have an advantage over urine cytology in terms of sensitivity, especially for detecting low grade, superficial tumors. However, most markers tend to be less specific than cytology, yielding more false-positive results. This scenario is more common in patients with concurrent bladder inflammation or other benign bladder conditions. However, there is reason to be optimistic about several new markers that appear to provide better specificity. Few urine based markers have been identified and investigated in other urological tumors. CONCLUSIONS: Detecting bladder cancer using diagnostic markers still presents a challenge. A number of new markers are currently available that appear to be significantly more accurate than cytology. However, further studies involving a larger number of patients are required to determine their accuracy and widespread applicability for diagnosing bladder cancer. Urine based markers do not appear to have a significant role in the diagnosis or prognosis of other urological malignancies, such as prostate, kidney or testicular cancer.

Urine cytology. It is still the gold standard for screening?

Urine cytology remains the gold standard for bladder cancer screening. It is the test against which all others are compared when evaluating potential bladder tumor markers. The answer to whether urine cytology possess the optimal combination of sensitivity and specificity to retain consideration as the best screening device depends on the goals of the clinical practice. Urine cytology has excellent specificity with few false-positive cases. Its overall sensitivity is poor, but this drawback is explained for the most part by poor criteria for identifying well-differentiated, low-grade TCC. The natural history of such lesions is the occurrence of multiple superficial recurrences in 70% to 80% of patients, with only a minority (10% to 15%) progressing to muscle invasive or metastatic disease. Because patients with low-grade TCC are at low risk for progression, they are monitored primarily for the development of a subsequent tumor. One might argue that the detection of new low-grade lesions is of secondary importance to the early detection of disease progression. The performance characteristics of urine cytology in this regard are much improved. Urine cytology often results in the identification of high-grade malignant cells even before a cystoscopically distinguishable gross lesion is present. Routinely diagnosing grade I TCC may be clinically irrelevant. Ancillary techniques to improve the sensitivity of urine cytology have been insufficiently additive to have much clinical value. Several promising bladder tumor markers have been investigated as potential screening tools and are summarized in Table 3. BTA, nuclear matrix proteins, and fibrin/fibrinogen degradation products share lower specificities than urine cytology and may have high rates of false positivity. Telomerase is highly sensitive and highly specific but is not readily available as a point-of-service test. Hyaluronidase and hyaluronic acid are promising prognostic markers, but hyaluronidase does not detect grade I TCC. Early results from studies of this marker await verification. Combining some of these new markers may optimize their performance status, allowing the advantages of one test to correct the shortcomings of another. Likewise, their combination with urine cytology may prove beneficial. Although adding urine cytology has not increased the sensitivity of some point-of-service tests, few studies have addressed the effect on specificity. Until an obvious winner is declared in the race to find a bladder tumor marker, urine cytology will remain the gold standard screening method because of its comfortable familiarity.

The utility of fibrin/fibrinogen degradation products in superficial bladder cancer.

Fibrin/fibrinogen degradation products are either absent or present at exceedingly low levels in the urine of healthy persons. Although various nonspecific inflammatory conditions of the urinary tract can result in detectable amounts of FDP in the urine, the presence of FDP is far more prevalent in urine from patients with bladder cancer. Urinary FDP levels tend to be higher in patients with tumors of increasing grade and stage. This correlation results in improved sensitivity in detecting more aggressive tumors. Current monoclonal antibody immunoassays are simple, rapid, and inexpensive, and can be performed on urine samples in the clinical setting. The overall accuracy of these immunoassays ranges from 75% to 80% (Table 1), suggesting that the urine FDP test should not be used alone for the surveillance of superficial bladder cancer. When assays for urine FDP are combined with urine cytology, the sensitivity for detecting tumors is improved. Prospective data are needed to determine whether using these tests in combination can safely permit a reduced frequency of endoscopic surveillance.

Update on urine-based markers for bladder cancer. How sensitive and specific are the new noninvasive tests?

Urine cytology is still the most commonly used noninvasive test to diagnose bladder cancer. However, cytology's ability to detect low-grade bladder tumors is limited, and its results require interpretation by a pathologist, are not available immediately, and are subjective. Several noninvasive urine-based tests are now available for detection and follow-up of bladder cancer. At least two of these new tests (BTA stat and AuraTek FDP) can easily be performed in the office, and the results are available in about 10 minutes. When choosing a test, physicians should keep in mind that none of the currently available tests is 100% accurate. However, the new urine-based tests are more sensitive than urine cytology and hence more reliable in detecting low-grade bladder cancer. They are useful tools in patients with urinary symptoms or microscopic hematuria or as office-based adjuncts to diagnostic procedures. Some of the markers that are being developed could significantly improve and simplify workup, diagnosis, and follow-up, and they may allow for detection of disease at an earlier stage, thus improving the chances of curative therapy.

A multicenter trial evaluation of the fibrin/fibrinogen degradation products test for detection and monitoring of bladder cancer.

PURPOSE: Presently there is a lack of effective, noninvasive tests for the detection and monitoring of bladder cancer. Measurement of fibrin/fibrinogen degradation products in urine has been shown to be a useful indicator of bladder carcinoma. The objective of this study was to evaluate the AuraTek FDP rapid immunoassay device for the detection of urinary fibrin/ fibrinogen degradation products associated with bladder cancer. MATERIALS AND METHODS: A prospective multicenter study was conducted to compare AuraTek FDP with urinary cytology and hemoglobin dipstick for the detection of bladder cancer in 192 patients with a history of bladder cancer. RESULTS: AuraTek FDP was significantly more sensitive (68%) than conventional urinary cytology (34%, p < 0.001) or hemoglobin dipstick (41%, p < 0.001) in the detection of bladder tumors, particularly for low stage low grade disease. In subjects with invasive disease (T2-T4) the AuraTek FDP test had a sensitivity of 100%. Specificity of AuraTek FDP was 96% for healthy subjects, 86% in patients with urological disease other than bladder cancer and 80% for patients under surveillance for bladder cancer but with a negative cystoscopic finding at the time of assay. CONCLUSIONS: This simple, rapid (less than 7 minutes) point of care test is superior to conventional urine cytology and hemoglobin dipstick as an aid in the detection of bladder cancer.

Left renal vein entrapment syndrome in two girls with orthostatic proteinuria.

Left renal vein entrapment was documented by bilateral ureteral catheterization and imaging studies as a cause of orthostatic proteinuria in two girls. Renal ultrasonography showed compression of the left renal vein between the aorta and the superior mesenteric artery (Nutcracker phenomenon). Abnormal collateral veins and high pressure gradients between the left renal vein and the inferior vena cava were found on left renal venography and pressure tracing, respectively. The left kidney was documented as the source of postural proteinuria by bilateral ureteral catheterization. Our observations suggest renal congestion due to left renal vein entrapment was the cause of orthostatic proteinuria.

Post-operative blood loss after transurethral prostatectomy is dependent on in situ fibrinolysis.

OBJECTIVE: To evaluate whether post-operative blood loss in patients with benign prostatic hyperplasia, undergoing transurethral resection of the prostate (TURP), depends on in situ fibrinolysis in urine, and to determine the relative contributions of the urokinase and tissue-type plasminogen activator systems. PATIENTS AND METHODS: TURP was performed in 24 men (median age 68.5 years, range 52-78) and the weight of resected tissue, the operative and post-operative blood loss determined. The concentrations of the urokinase- (u-PA) and tissue-type plasminogen activator (t-PA)-related fibrinolysis in their urine was followed using sensitive and specific assays, and the changes related to post-operative blood loss. Measurements of the urinary concentrations of free t-PA activity, t-PA antigen, free u-PA activity, u-PA antigen and fibrin degradation products (FbDP) were determined and the area under the curve for each of these quantities correlated with the post-operative blood loss. RESULTS: The post-operative blood loss correlated significantly with the per-operative loss (P = 0.047) and the weight of resected tissue (P = 0.029). There was a highly significant correlation between the area under the curve of FbDP in the urine and the post-operative blood loss (P < 0.005), while there was no significant positive correlation between the PA concentration or activity in the urine and post-operative blood loss. There was a significant correlation between the urinary t-PA activity and the amount of FbDP in the urine (P = 0.047), and a significant correlation between the weight of resected tissue and the amount of FbDP in the urine (P = 0.014). CONCLUSION: The post-operative blood loss after TURP is significantly related to an increase of the urinary fibrinolytic activity and the enhanced fibrinolytic activity is probably caused by t-PA.