Investigating selected adhesion molecules as urinary biomarkers for diagnosing endometriosis.

RESEARCH QUESTION: Are selected cell adhesion molecules useful as urinary biomarkers for diagnosing endometriosis? DESIGN: Prospective, longitudinal study (the Endometriosis Marker Austria) in patients who underwent laparoscopic surgery for benign gynaecological pathologies. A total of 149 patients not receiving hormonal treatment for at least 3 months prior to recruitment were included and preoperative urine protein levels of soluble vascular adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), E-selectin and P-selectin were measured using a magnetic bead-based multiplex assay, normalized to creatinine levels of each sample. Levels were correlated with endometriosis status, menstrual cycle phase, body mass index, cigarette smoking and severity and entity of the lesions. RESULTS: Urine levels of sVCAM-1, sICAM-1, E-selectin and P-selectin did not differ between women with (n = 84) and without (n = 65) endometriosis and among subgroups. Accordingly, receiver operating characteristic analysis to examine the value of using sVCAM-1, sICAM-1, E-selectin and P-selectin levels and sVCAM/sICAM ratio to diagnose endometriosis were not significant. Whether the serum sVCAM-1 levels correlated with the urine levels of the protein in the same women was also investigated, which revealed no significant correlations for sVCAM or sICAM. CONCLUSION: Although a previous study had suggested that serum sVCAM is a promising biomarker for diagnosing endometriosis, no significant differences were found in urine levels of sVCAM-1, sICAM-1, E-selectin and P-selectin between women with and without endometriosis. Other markers should be studied in an effort to establish a truly non-invasive urinary test for diagnosing endometriosis.

IL-18, VCAM-1 and P-selectin as early biomarkers in normoalbuminuric Type 2 diabetes patients.

Aim: To investigate the pathophysiological role of different biomarkers in diabetic kidney disease (DKD) among normoalbuminuric patients with a low-estimated glomerular filtration rate (eGFR). Methods: In this cross-sectional study of 200 normoalbuminuric Type 2 diabetes patients, 28 patients (14%) had a low eGFR. Results: The IL-18, VCAM-1 and P-selectin levels were significantly higher at a low eGFR. On analyzing the area under the receiver operating characteristic curve, these biomarkers had significant diagnostic value and have important pathophysiological role in the progression of DKD. Conclusion: Among normoalbuminuric Type 2 diabetes patients, IL-18, VCAM-1 and P-selectin may play a significant role in the prediction of early DKD. Further prospective studies need to be conducted to confirm this observation.

Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance.

OBJECTIVE: Currently, proteinuria is viewed as the earliest indicator of renal disease in immune-mediated nephritis. The objective of this study was to determine whether additional mediators may be excreted in the urine during immune-mediated nephritis, using an experimental model with a well-defined disease course. METHODS: Urine samples from mice with anti-glomerular basement membrane (anti-GBM) antibody-induced experimental nephritis were screened using a focused immunoproteome array bearing 62 cytokines/chemokines/soluble receptors. Molecules identified through this screening assay were validated using an enzyme-linked immunosorbent assay. One of these molecules was further evaluated for its pathogenic role in disease, using antibody-blocking studies. RESULTS: Compared with B6 and BALB/c mice, in which moderately severe immune-mediated nephritis develops, the highly nephritis-susceptible 129/Sv and DBA/1 mice exhibited significantly increased urinary levels of vascular cell adhesion molecule 1 (VCAM-1), P-selectin, tumor necrosis factor receptor I (TNFRI), and CXCL16, particularly at the peak of disease. Whereas some of the mediators appeared to be serum derived early in the disease course, local production in the kidneys appeared to be an important source of these mediators later in the course of disease. Both intrinsic renal cells and infiltrating leukocytes appeared to be capable of producing these mediators. Finally, antibody-mediated blocking of CXCL16 ameliorated experimental immune nephritis. CONCLUSION: These studies identified VCAM-1, P-selectin, TNFRI, and CXCL16 as a quartet of molecules that have potential pathogenic significance; the levels of these molecules are significantly elevated during experimental immune nephritis. The relevance of these molecules in spontaneous immune nephritis warrants investigation.

[Renal protective effect of nilestriol in aged women with hypertension].

OBJECTIVE: To investigate the renal protective effect of nilestriol in aged hypertensive women. METHODS: Forty-one aged hypertensive women treated with antihypertensive drugs were randomly divided into two groups. The women in Group A (n = 21) received nilestriol, whereas those in Group B (n = 20) received a placebo for six months. Antihypertensive drugs were unchanged. Twenty-four healthy subjects were set as the normal control group. RESULTS: 1. Before the treatment, the levels of urinary transferrin (TRF), retinol binding protein (RBP), P-selectin, vWF, and ET-1 were significantly higher in the aged hypertensive women than those in the control group. 2. The levels of TRF and RBP significantly decreased in both Group A and Group B after the 6-month treatment, but these levels in Group A were significantly lower than those in Group B (P < 0.05). 3. The levels of P-selectin, vWF, and ET-1 in Group A were significantly lower than those in Group B (P < 0.05-0.01) after the treatment. CONCLUSION: 1. In aged hypertensive women treated with antihypertensive drugs, the renal function is still damaged; 2. Nilestriol can significantly decrease the levels of TRF and RBP; 3. The renal protective effect of nilestriol may be related to the protection of endothelin function and antithrombosis activity.