Effects of angiogenic factors, antagonists, and podocyte injury on development of proteinuria in preeclampsia.

Proteinuria is universal to all patients with preeclampsia. We examined the urinary podocytes in women with preeclampsia (n = 14), gestational hypertension (n = 14), and normal pregnancy. Maternal serum and urinary concentrations of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and the antiangiogenic factor soluble fms-like tyrosine kinase 1 (sFlt-1) were detected. These concentrations were used to evaluate the urinary excretion of podocytes and the alteration of angiogenic factors and to assess their relationships to proteinuria in preeclampsia. Our studies suggest that the urinary podocyte number and angiogenic factors are correlated with random urine albumin/creatinine ratio and blood pressure. Receiver-operating characteristic (ROC) curves of serum and urinary PlGF and the PlGF/sFlt-1 ratio as well as the presence of podocyturia confirmed their usefulness in distinguishing preeclamptic and normotensive pregnant women. In addition, combinations of serum or urinary PlGF or podocyturia tests in parallel or in series provided the best clue for identifying patients with preeclampsia. We considered that the dysregulation of angiogenic factors and its subsequent podocyte injury may contribute to the mechanism of proteinuria development in preeclampsia.

[Urine-based markers of angiogenesis in bladder cancer]. / Urinbasierte Angiogenesemarker beim Urothelkarzinom der Harnblase.

Angiogenesis is a prerequisite for tumour growth and metastasis. Therefore, angiogenesis factors in bladder cancer, a common disease of the genitourinary tract, could serve as diagnostic tools, predictors of prognosis, and targets for therapy. Development of less invasive or noninvasive detection techniques, reliable prognostic markers, and individualized targeted therapy would have a significant impact on disease management. For this investigative goal, the utility of urine and blood is beneficial. Research in the field of angiogenesis and promising markers is currently evolving. In spite of the recent success of antiangiogenic agents in the oncological clinic, an optimal marker that will warrant substitution of the cystoscopic follow-up protocol in patients with urothelial neoplasms has not been identified yet. Despite this challenge, allocating more resources and attention to identifying such urine markers is justified to optimize the diagnostics and follow-up of urinary bladder cancer.

A panel of angiogenic factors for early bladder cancer detection: enzyme immunoassay and Western blot.

PURPOSE: Angiogenesis is tightly regulated by a large number of pro-angiogenic factors, including vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and angiogenin. We adapted and evaluated the measurement of these factors using enzyme-linked immunosorbent assay and compared the results with Western blot and voided urine cytology. MATERIALS AND METHODS: This study included 240 patients diagnosed with bladder carcinoma, 108 with benign bladder lesions and 110 healthy individuals who served as controls. All participants underwent serological schistosomiasis antibody assay in serum, urine cytology and estimation of angiogenic factors in voided urine. RESULTS: Intra-assay and interassay CVs of the investigated markers were 10.3 to 12.3 and 10 to 13.7, respectively. The recovery rate of the added angiogenic factor to the urine pool was 98% to 103%, 97% to 103%, 98% to 104% and 97% to 100% for vascular endothelial growth factor, basic fibroblast growth factor, angiogenin and hepatocyte growth factor, respectively. The concordance rate with Western blot was 97.5%. The levels and positive rates of urinary angiogenic markers and urine cytology were significantly higher in the malignant group than in the benign and healthy groups. Basic fibroblast growth factor increased significantly in bladder squamous cell carcinoma cases. Moreover, basic fibroblast growth factor and hepatocyte growth factor significantly correlated with tumor grade. Angiogenic markers showed significant association with clinical stage. CONCLUSIONS: Quantitative measurement of urinary angiogenic factors in voided urine samples by enzyme-linked immunosorbent assay was reliable. The sensitivity of basic fibroblast growth factor and hepatocyte growth factor was superior to that of the other investigated markers and of cytology in low grade and early stage cases, suggesting their convenience as sensitive, noninvasive diagnostic and screening tools for bladder cancer.