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1.
Reprod Biomed Online ; 40(4): 555-558, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32220518

ABSTRACT

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.


Subject(s)
E-Selectin/metabolism , Endometriosis/diagnosis , Intercellular Adhesion Molecule-1/urine , P-Selectin/urine , Vascular Cell Adhesion Molecule-1/urine , Adult , Biomarkers/urine , Diagnosis, Differential , Endometriosis/urine , Female , Humans
2.
Immunol Invest ; 49(1-2): 15-31, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31298049

ABSTRACT

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology. Intercellular cell adhesion molecule-1 (ICAM-1) is critical for leukocyte adhesion to endothelium and migration out of blood vessels and thus participates in many autoimmune diseases. Previous studies of blood and urinary ICAM-1 in SLE have yielded inconsistent results.Methods: The following databases were searched for studies that compared blood and/or urinary ICAM-1 in SLE patients vs. healthy control subjects, and/or in SLE with active vs. inactive diseases: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Web of Science. Standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using a random-effects model when there was significant heterogeneity (assesses using the Cochrane Q test and I2 statistics), and using a fixed-effects model otherwise. Publication bias was assessed using funnel plot and egger text.Results: The initial screening yielded a total of 1,215 articles; 22 articles (14 reporting blood ICAM-1, 7 reporting urinary ICAM-1 and 1 reporting both) were included in the meta-analysis. In comparison to healthy controls, SLE patients had elevated urinary ICAM-1 (SMD: 0.711; 95% CI: 0.521, 0.901) as well as blood ICAM-1 (SMD: 0.725; 95% CI: 0.385, 1.065). Blood ICAM-1 did not differ significantly between active and inactive SLE (SMD: 0.396; 95% CI: -0.556, 1.347).Conclusion: Elevated blood and urinary ICAM-1 is a biomarker for SLE, but does not differentiate active and inactive SLE.


Subject(s)
Biomarkers/blood , Biomarkers/urine , Intercellular Adhesion Molecule-1/blood , Intercellular Adhesion Molecule-1/urine , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/urine , Humans
3.
Eur J Immunol ; 49(2): 323-335, 2019 02.
Article in English | MEDLINE | ID: mdl-30537116

ABSTRACT

Non-classical monocytes infiltrate the kidney parenchyma and participate in tissue damage in patients with lupus nephritis (LN). Circulating microparticles (MPs) seem to play critical roles in the activation of monocytes in systemic lupus erythematosus (SLE) patients. This study aims to characterize the phenotypes of MPs and monocyte subsets in LN patients and to determine their potential to discriminate between SLE patients with and without LN. Blood and urine samples from SLE patients were collected. In monocyte subsets from whole blood samples several phenotypic markers were evaluated. MPs were isolated from platelet-poor plasma and urine by centrifugation. This phenotypic marker characterization was performed using multiparametric flow cytometry. We observed that patients with active LN have lower counts of non-classical monocytes than do those without renal involvement. All monocyte subsets exhibited lower expression of CX3CR1 and ICAM-1 in LN than in patients without LN. High frequencies of MP-HMGB1+ and MP-HLA-DR+ were detected in circulation and urine of LN patients. Although MP-HMGB1+ , MP-HLA-DR+ , and MP-CX3CR1+ from urine were able to discriminate between patients with and without LN, only urinary MP-HMGB1+ were different between patients with active and inactive LN. Therefore, these vesicles may be useful as biomarkers of LN.


Subject(s)
Cell-Derived Microparticles/metabolism , HMGB1 Protein/metabolism , HMGB1 Protein/urine , Lupus Nephritis/urine , Monocytes/metabolism , Adolescent , Adult , Biomarkers/blood , Biomarkers/urine , CX3C Chemokine Receptor 1/blood , Female , HLA-DR Antigens/blood , HLA-DR Antigens/urine , HMGB1 Protein/blood , Humans , Intercellular Adhesion Molecule-1/blood , Intercellular Adhesion Molecule-1/urine , Lupus Nephritis/blood , Male , Middle Aged
4.
BMC Nephrol ; 19(1): 358, 2018 12 14.
Article in English | MEDLINE | ID: mdl-30547763

ABSTRACT

BACKGROUND: IgA nephropathy (IgAN) is one of the most common forms of idiopathic glomerular diseases and might lead to end-stage kidney disease. Accurate and non-invasive biomarkers for early diagnosis are required for early intervention and consequent therapy for IgAN patients. Because variance in the disease incidence and predisposing genes of IgAN has been detected among different ethnicities, the ethnicity factor should be considered in IgAN biomarker discovery. The differences in the protein profiles and pathological mechanisms of IgAN in patients of Uygur ethnicity need to be clearly illustrated. METHODS: In this study, we used urinary proteomics to discover candidate biomarkers of IgAN in patients of Uygur ethnicity. The urinary proteins from Uygur normal control and Uygur IgAN patients were extracted and analyzed using 2D-LC-MS/MS and isobaric tags for relative and absolute quantitation (iTRAQ) analysis. RESULTS: A total of 277 proteins were found to be differentially represented in Uygur IgAN compared with the respective normal controls. The bioinformatics analysis revealed that the immune response, cell survival, and complement system were activated in Uygur IgAN. Many differentially expressed proteins were found to be related to nephropathy and kidney injuries. Four candidate biomarkers were validated by Western blot, and these results were consistent with the iTRAQ results. ICAM1, TIMP1, SERPINC1 and ADIPOQ were upregulated in Uygur IgAN. Bioinformatic analysis revealed that the increase of ICAM1 and TIMP1 might be caused by IgAN, but the increase of SERPINC1 and ADIPOQ might be caused by proteinuria. SERPINC1 and ICAM1 were identified as the candidate biomarkers with excellent area-under-the-curve (AUC) values (0.84) for distinguishing Uygur IgAN from normal controls. CONCLUSIONS: Using urinary proteomic analysis, we identified several candidate biomarkers for IgAN in patients of Uygur ethnicity. These results will prove helpful for exploring the pathological mechanism of IgAN in patients of Uygur ethnicity and for developing better treatments for these patients.


Subject(s)
Adiponectin/urine , Antithrombin III/urine , Glomerulonephritis, IGA/urine , Intercellular Adhesion Molecule-1/urine , Proteinuria/urine , Tissue Inhibitor of Metalloproteinase-1/urine , Adult , Area Under Curve , Asian People , Biomarkers/urine , Case-Control Studies , China , Female , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/ethnology , Glomerulonephritis, IGA/immunology , Humans , Male , Middle Aged , Proteinuria/etiology , Proteome/metabolism , Proteomics
5.
Medicine (Baltimore) ; 97(26): e11287, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29953010

ABSTRACT

The current methods of monitoring the activity of lupus nephritis (LN) may cause unnecessary hospital visits or delayed immunosuppressive therapy. We aimed to find a urinary biomarker that could be developed as a home-based test for monitoring the activity of LN.Urine samples were collected immediately before a renal biopsy from patients of suspected active LN, and also from patients with inactive LN, systemic lupus erythematous without LN or healthy controls. Biomarker search was conducted on a cytokine antibody array and confirmation was done by quantitative evaluation with enzyme-linked immunosorbent assay. The Mann-Whiney test or Student t test was used to compare the levels of 9 cytokines between different groups. The sensitivity and specificity of each cytokine for diagnosis of LN was evaluated by receiver operating characteristic curve. A rapid test based on colloidal gold immunochromatography was then developed for bedside or home use. Furthermore, an experimental e-healthcare system was constructed for recording and sharing the results of the rapid test a cloud-assisted internet of things (IoT) consisting of a sensing device, an IoT device and a cloud server.Adiponectin (Acrp30), soluble intercellular cell adhesion molecule-1 (sICAM-1), neural cell adhesion molecule 1 (NCAM-1), and CD26 were significantly higher in urine samples of active LN patients. sICAM-1 appeared more sensitive and specific among these candidates. When the cut-off value of sICAM-1 was set at 1.44 ng/mL, the sensitivity reached 98.33% with a specificity at 85.71%. The sICAM-1 strip test showed comparable sensitivity of 95% and a specificity of 83.3% for assessing the LN activity. Meanwhile, the e-healthcare system was able to conveniently digitize and share the sICAM-1 rapid test results.sICAM-1 appeared to be an excellent biomarker for monitoring LN activity. The e-healthcare system with cloud-assisted IoT could assist the digitalization and sharing of the bedside or home-based sICAM-1 test results.


Subject(s)
Intercellular Adhesion Molecule-1/urine , Lupus Nephritis/immunology , Lupus Nephritis/urine , Adiponectin/immunology , Adiponectin/urine , Adult , Aged , Biomarkers , CD56 Antigen/immunology , CD56 Antigen/urine , Dipeptidyl Peptidase 4/immunology , Dipeptidyl Peptidase 4/urine , Enzyme-Linked Immunosorbent Assay , Female , Humans , Intercellular Adhesion Molecule-1/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/urine , Male , Middle Aged , Severity of Illness Index
6.
Biomarkers ; 21(2): 123-8, 2016.
Article in English | MEDLINE | ID: mdl-26631256

ABSTRACT

AIM: We aimed to investigate whether urine intercellular adhesion molecule-1 (ICAM-1) might serve as a marker of renal disorder in children with ureteropelvic junction obstruction. MATERIAL AND METHODS: Twenty-nine children with severe hydronephrosis (HN) were compared with 23 participants with mild HN and with 19 healthy peers. RESULTS: Urine ICAM-1/uCre levels were significantly higher in HN children than healthy controls (P<0.01), and in severe HN when compared with mild HN (p<0.05). CONCLUSIONS: It seemed to us that uICAM-1 is a biomarker of renal disorder, and might have the potential to predict which patients will require surgery.


Subject(s)
Biomarkers/urine , Intercellular Adhesion Molecule-1/urine , Kidney Diseases/urine , Ureteral Obstruction/urine , Analysis of Variance , Case-Control Studies , Child , Child, Preschool , Female , Humans , Hydronephrosis/diagnosis , Hydronephrosis/urine , Infant , Kidney Diseases/diagnosis , Male , Prognosis , ROC Curve , Severity of Illness Index , Ureteral Obstruction/diagnosis
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 35(9): 1272-6, 1282, 2015 Aug.
Article in Chinese | MEDLINE | ID: mdl-26403737

ABSTRACT

OBJECTIVE: To determine the levels of urinary soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) in patients with lupus nephritis (LN), and explore their correlation with renal disease activity. METHODS: Urine samples were collected from 92 renal biopsy-proven LN patients and 20 healthy controls. Renal disease activity was determined according to the ISN/RPS 2003 Revised Classification of Lupus Nephritis. The urine levels of sICAM-1 and VCAM-1 were detected by enzyme-linked immunosorbent assay, and the expressions of intrarenal ICAM-1 and VCAM-1 were evaluated by immunohistochemisty staining. RESULTS: Urinary sICAM-1 and VCAM-1 levels were elevated in LN patients compared with the controls. Significantly higher levels of urinary sICAM-1 and VCAM-1 were found in patients with active LN, who had also significantly increased intrarenal expressions of ICAM-1 and VCAM-1 compared with patients in remission. A strong positive correlation was noted between intrarenal expression and urine levels of ICAM-1 and VCAM-1. The receiver-operating characteristic (ROC) curve of urine sICAM-1 showed tan area under ROC curve of 0.874 for all participants in the test. A cutoff of 1095.00 pg/mg creatinine yielded a good sensitivity (0.945) and specificity (0.789). The ROC curve of urine VCAM-1 showed an area under ROC of 0.882 for all the participants, and a cutoff of 898.11 pg/mg creatinine yielded a good sensitivity (0.982) and specificity (0.667). CONCLUSION: Urine sICAM-1 and VCAM-1 levels are positively correlated with their intrarenal expressions and reflect the activity of the nephritis, and therefore they may serve as potential biomarkers for early diagnosis of active LN.


Subject(s)
Biomarkers/urine , Intercellular Adhesion Molecule-1/urine , Lupus Nephritis/diagnosis , Vascular Cell Adhesion Molecule-1/urine , Case-Control Studies , Early Diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Kidney/metabolism , Lupus Nephritis/urine , ROC Curve , Sensitivity and Specificity
8.
J Pharmacol Exp Ther ; 343(1): 34-43, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22736507

ABSTRACT

Progression of hyperglycemia-induced renal injury is a contributing factor for diabetic nephropathy (DN)-induced end-stage renal disease (ESRD), and development of novel therapeutic strategies that act early to prevent progression of DN and ESRD are important. We examined the efficacy and mechanism(s) of suramin on hyperglycemia-induced renal injury before development of overt histological damage. Two groups of male Sprague-Dawley rats received streptozotocin (STZ) and one group received saline. Three weeks later, one STZ group received suramin (10 mg/kg). All animals were euthanized 1 week later (4 weeks). Although there was a decrease in creatinine clearance between control and STZ ± suramin rats, there was no difference in creatinine clearance between STZ rats ± suramin intervention. Liquid chromatography-tandem mass spectroscopy-based analysis revealed increases in urinary proteins that are early indicators of DN (e.g., cystatin C, clusterin, cathepsin B, retinol binding protein 4, and peroxiredoxin-1) in the STZ group, which were blocked by suramin. Endothelial intracellular adhesion molecule-1 (ICAM-1) activation, leukocyte infiltration, and inflammation; transforming growth factor-ß1 (TGF-ß1) signaling; TGF-ß1/SMAD-3-activated fibrogenic markers fibronectin-1, α-smooth muscle actin, and collagen 1A2; activation of proinflammatory and profibrotic transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription factor-3 (STAT-3), respectively, were all increased in STZ rats and suramin blocked these changes. In conclusion, delayed administration of suramin attenuated 1) urinary markers of DN, 2) inflammation by blocking NF-κB activation and ICAM-1-mediated leukocyte infiltration, and 3) fibrosis by blocking STAT-3 and TGF-ß1/SMAD-3 signaling. These results support the potential use of suramin in DN.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/urine , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/urine , Suramin/therapeutic use , Animals , Biomarkers/urine , Diabetes Mellitus, Experimental/complications , Diabetic Nephropathies/etiology , Intercellular Adhesion Molecule-1/urine , Kidney Failure, Chronic/drug therapy , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/urine , Male , NF-kappa B/urine , Random Allocation , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1/urine , Treatment Outcome
9.
Lupus ; 21(11): 1190-5, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22685016

ABSTRACT

BACKGROUND: Urinary intercellular adhesion molecule-1 (ICAM-1) level is potentially a valuable biomarker of lupus nephritis (LN), but because ICAM-1 is a cell-surface molecule, soluble ICAM-1 level in urinary supernatant measured by ELISA may not be biologically relevant. METHODS: The ICAM-1 level in urine sediment of 12 LN patients, 10 patients with pauci-immune necrotizing glomerulonephritis (NecGN), and six healthy controls were determined with a polymerase chain reaction (PCR)-based assay. The urinary sediment levels of miR-221, miR-222, miR-339-3P and miR-339-5P, which are involved in the regulation of ICAM-1 production, were also quantified. RESULTS: LN patients had lower urinary sediment ICAM-1 levels than the other two groups (overall p = 0.034). In addition, urinary sediment ICAM-1 level inversely correlated with the estimated glomerular filtration rate (GFR) (r = -0.474, p = 0.026) but not other markers of lupus activity, or urinary sediment levels of miR-221, miR-222, miR-339-3P, or miR-339-5P. However, serum anti-dsDNA level inversely correlated with urinary sediment levels of miR-221 (r = -0.591, p = 0.043) and miR-222 (r = -0.689, p = 0.013), while urinary sediment miR-221 level also correlated with serum C3 level (r = 0.658, p = 0.02). CONCLUSIONS: We conclude that urinary sediment ICAM-1 level was significantly reduced in LN, and the level inversely correlated with renal function. Urinary sediment miR-221 and miR-222 levels correlate with lupus disease activity and may serve as biomarkers of LN.


Subject(s)
Glomerulonephritis/physiopathology , Intercellular Adhesion Molecule-1/urine , Lupus Nephritis/physiopathology , MicroRNAs/urine , Adult , Aged , Autoantibodies/immunology , Biomarkers/urine , Case-Control Studies , DNA/immunology , Enzyme-Linked Immunosorbent Assay , Female , Glomerular Filtration Rate , Glomerulonephritis/urine , Humans , Lupus Nephritis/urine , Male , Middle Aged , Polymerase Chain Reaction
10.
Int J Rheum Dis ; 15(1): 13-6, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22324942

ABSTRACT

AIM: We sought to evaluate the relationship of urine levels of soluble cellular adhesion molecules sVCAM-1 (vascular) and sICAM-1 (intercellular) in systemic lupus erythematosus (SLE) patients with or without lupus nephritis, and to explore their correlation with renal disease activity. METHODS: Paired serum and urine samples of 121 Asian SLE patients, and urine samples of 19 normal healthy controls were collected. Demographic data, disease activity and damage scores, and selected laboratory parameters, including levels of anti-double stranded DNA antibody, complements C3, C4, and creatinine were captured. Renal disease activity was scored with renal SLE Activity Measure revised (rSLAM-R). Serum and urine sVCAM-1 and sICAM-1 levels were assayed by enzyme-linked immunosorbent assay. RESULTS: Urinary sVCAM-1 and sICAM-1 were elevated in SLE patients compared to controls. Significantly higher levels of urine sVCAM-1 found in patients with active lupus nephritis correlated with rSLAM-R. In addtion, significantly more patients with active lupus nephritis had detectable levels of urine sICAM-1, but no correlation with renal activity was observed. CONCLUSION: Urinary sVCAM-1 may serve as a potential biomarker for early diagnosis of lupus nephritis as levels correlated with even mild abnormalities of urine sediment. In addition, both urine sVCAM-1 and sICAM-1 levels may be useful in identifying patients at risk of lupus nephritis.


Subject(s)
Intercellular Adhesion Molecule-1/urine , Lupus Nephritis/diagnosis , Vascular Cell Adhesion Molecule-1/urine , Adult , Biomarkers/blood , Biomarkers/urine , Case-Control Studies , Early Diagnosis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Intercellular Adhesion Molecule-1/blood , Logistic Models , Lupus Nephritis/blood , Lupus Nephritis/immunology , Lupus Nephritis/urine , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Severity of Illness Index , Singapore , Up-Regulation , Vascular Cell Adhesion Molecule-1/blood
11.
Diabetes Res Clin Pract ; 95(1): 55-61, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21945031

ABSTRACT

AIMS: Our study addressed the influence of early inflammatory stages of diabetic kidney disease: leukocyte adhesion and monocyte activation (as assessed by intercellular leukocyte adhesion molecule-ICAM-1 and monocyte chemoatractant protein-MCP-1) on the degree of albuminuria. Plasma levels of adiponectin, a possible anti-inflammatory counteracting mechanism, were also studied in correlation to the above-mentioned cytokines. METHODS: 79 consecutive type 2 diabetic outpatients and 46 controls were included. Routine laboratory analysis, urinary albumin to creatinine ratio (uACR), plasma adiponectin, plasma ICAM-1 and urinary MPC-1 were assessed. RESULTS: In multiple regression ICAM-1 (p=0.004) and adiponectin (p=0.04) were the main determinants of uACR. Plasma adiponectin positively correlated to ICAM-1 (p=0.03, r=0.24). In albuminuric patients (uACR ≥30 mg/g) plasma adiponectin was significantly higher compared to normoalbuminuric ones (uACR <30 mg/g). In albuminuric patients the main determinants of uACR were plasma ICAM-1 and adiponectin. In multiple regression ICAM-1 is the only one that retains statistical significance (p=0.02). Urinary MCP-1 did not correlate to uACR. CONCLUSIONS: In our type 2 diabetic patients, plasma levels of ICAM-1 and adiponectin are predictive for albuminuria. Urinary MCP-1 does not correlated to uACR. Plasma adiponectin positively correlates to adhesion molecule ICAM-1 in our cohort.


Subject(s)
Adiponectin/blood , Albuminuria/blood , Diabetes Mellitus, Type 2/blood , Diabetic Nephropathies/blood , Intercellular Adhesion Molecule-1/blood , Aged , Aged, 80 and over , Albuminuria/urine , Chemokine CCL2/blood , Creatinine/blood , Creatinine/urine , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/urine , Diabetic Nephropathies/urine , Female , Humans , Inflammation/blood , Inflammation/urine , Intercellular Adhesion Molecule-1/urine , Kidney Function Tests , Male , Middle Aged
12.
Diabet Med ; 29(5): 567-77, 2012 May.
Article in English | MEDLINE | ID: mdl-21913962

ABSTRACT

Novel biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes have been recently identified. We performed a systematic review to assess the validity of biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes in longitudinal studies. The methodological quality of the studies was scored using Standards for Reporting of Diagnostic Accuracy (STARD) criteria and the independent predictive value of the biomarkers beyond conventional risk factors was scored according to the adjustment for these risk factors. Validity of the biomarkers was determined by summarizing the methodological quality and the adjustment score. We identified 15 studies describing 27 biomarkers. Six studies had sufficient methodological quality. These studies identified 13 valid and significant markers for nephropathy in diabetes: serum interleukin 18, plasma asymmetric dimethylarginine; and urinary ceruloplasmin, immunoglobulin G and transferrin were considered valid markers predicting onset of nephropathy. Plasma asymmetric dimethylarginine, vascular cell adhesion molecule 1, interleukin 6, von Willebrand factor and intercellular cell adhesion molecule 1 were considered valid biomarkers predicting progression of nephropathy. Plasma high-sensitivity C-reactive protein, E-selectin, tissue-type plasminogen activator, von Willebrand factor and triglycerides were considered valid markers predicting onset and progression of nephropathy. Several novel biomarkers for prediction of nephropathy in diabetes have been published, which can potentially be applied in clinical practice and research in future. Because of the heterogeneous quality of biomarker studies in this field, a more rigorous evaluation of these biomarkers and validation in larger trials are advocated.


Subject(s)
Albuminuria/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/physiopathology , Albuminuria/blood , Albuminuria/urine , Biomarkers/blood , Biomarkers/urine , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/surgery , Diabetic Nephropathies/blood , Diabetic Nephropathies/urine , Disease Progression , Endothelium, Vascular , Female , Humans , Intercellular Adhesion Molecule-1/blood , Intercellular Adhesion Molecule-1/urine , Interleukin-6/blood , Interleukin-6/urine , Male , Predictive Value of Tests , Vascular Cell Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/urine , von Willebrand Factor/urine
13.
Clin Exp Nephrol ; 14(6): 548-57, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20714774

ABSTRACT

BACKGROUND: Leukocyte adhesion molecules are important for migration of the inflammatory cells into sites of inflammation. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin superfamily that are expressed in normal kidney. Their expression is up-regulated in the renal tissue of patients with lupus nephritis (LN). OBJECTIVES: We evaluated whether changes in urinary levels of ICAM-1 and VCAM-1 reflect renal tissue damage in LN. We related the levels of these molecules to other laboratory findings, especially complement C3/C4 levels. We also tested the hypothesis that changes in urinary levels of ICAM-1 and VCAM-1 reflect the severity of renal tissue damage in LN. PATIENTS AND METHODS: This study included 30 systemic lupus erythematosus (SLE) patients with LN (16 with mild histological changes, i.e., with World Health Organization (WHO) class I and II LN, and 14 with advanced histological changes, i.e., class III, IV, and V LN) and 20 with SLE without nephritis. In addition, 20 healthy individuals of comparable age were included as a control group. The levels of urinary ICAM-1 and VCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) and related to the clinical, laboratory [rheumatoid factor(RF), antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), complements C3 and C4] and histological findings. RESULTS: Levels of urinary ICAM-1 and VCAM-l in LN patients with advanced histological changes (renal damage) were statistically significantly higher than those in other groups (LN patients with mild histological changes or SLE patients without nephritis and control group; p < 0.01). In contrast, serum levels of C3 and C4 in LN patients with advanced histological changes were significantly lower than those in other groups (p < 0.01). There was a significant negative correlation between the levels of urinary adhesion molecules and serum complement levels (p < 0.01). CONCLUSIONS: The significantly high urinary levels of the adhesion molecules in the LN group with advanced histological changes may reflect their renal tissue expression and therefore the severity of the nephritis. Renal tissue damage in these cases may be the result of transmigration of activated inflammatory cells, inducing serious tissue damage. The hypocomplementemia combined with increased urinary levels of adhesion molecules seems to be a useful biomarker of disease severity in LN.


Subject(s)
Intercellular Adhesion Molecule-1/urine , Kidney/immunology , Lupus Nephritis/urine , Vascular Cell Adhesion Molecule-1/urine , Adult , Complement C3/metabolism , Complement C4/metabolism , Female , Humans , Kidney/pathology , Lupus Nephritis/pathology , Male
14.
Eur J Clin Invest ; 39(11): 980-5, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19663918

ABSTRACT

BACKGROUND: Nowadays, intensive insulin treatment has been widely used in type 2 diabetics who have poor control of blood glucose, to reduce the risk of chronic complications of diabetes. Recently, some scholars have paid more attention to the pivotal role of inflammation involved in type 2 diabetes and its complications. Monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1), which are two important inflammatory chemokines, have been documented to participate in the onset and development of type 2 diabetes and its complications, such as diabetic nephropathy (DN). DESIGN: In the current study, we recruited 30 type 2 diabetics with microalbuminuria to be treated with multiple insulin injections daily for 2 weeks. Random spot urine samples (corrected for creatinine-Cr) were collected for the examination of urinary MCP-1, ICAM-1 and albumin (Alb) levels before and after the intensive insulin therapy. Changes in their levels were observed to test the hypothesis that type 2 diabetes with microalbuminuria is associated with elevated urinary concentrations of MCP-1 and ICAM-1, and intensive insulin therapy can result in a decline of Alb by reducing the inflammatory reaction. RESULTS: The urinary MCP-1/Cr and urinary ICAM-1/Cr ratios in type 2 diabetic patients with microalbuminuria were much higher than those in normal controls, and intensive insulin treatment could decrease significantly the urinary MCP-1/Cr, ICAM-1/Cr and Alb/Cr ratios in type 2 diabetics with microalbuminuria. CONCLUSION: Intensive insulin treatment may protect against renal injury in early DN by reducing the urinary MCP-1 and ICAM-1 excretions.


Subject(s)
Albuminuria/urine , Chemokine CCL2/urine , Diabetes Mellitus, Type 2/urine , Diabetic Nephropathies/urine , Intercellular Adhesion Molecule-1/urine , Kidney/metabolism , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/physiopathology , Female , Humans , Kidney/physiopathology , Male , Middle Aged
15.
J Endocrinol Invest ; 32(11): 877-80, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20134257

ABSTRACT

OBJECTIVE: To observe the change of urinary intercellular adhesion molecule-1 (ICAM-1) excretion in the patients with Type 2 diabetes mellitus (T2DM) compared to normal control group, and to investigate the effect and significance of insulin intensive therapy on the urinary ICAM-1 excretion. METHOD: We examined the urinary ICAM-1 and creatinine (Cr) of random urine in 20 patients with T2DM and 20 normal subjects using enzyme-linked immunosorbent assay. All diabetics were given intensive insulin therapy for 2 weeks, urinary ICAM- 1 and Cr was examined once again at the end of observation. RESULTS: Compared with the normal control group, not only the fasting blood glucose (FBG), post-prandial 2-h blood glucose (P2hBG), and glycosylated hemoglobin (HbA1c), but also the urinary ICAM-1 to urinary Cr ratio in patients with T2DM increased significantly (p<0.01). The urinary ICAM-1/urinary Cr ratio of diabetics had a positive correlation with FBG (r=0.51, p<0.01), P2hBG (r=0.496, p<0.01), and HbA1c (r=0.478, p<0.05), respectively. After 2 weeks of intensive insulin therapy in Type 2 diabetics, both the level of blood glucose and the level of urinary ICAM-1/urinary Cr ratio had a remarkable decrease compared with the basal values (p<0.01). CONCLUSION: Intensive insulin therapy is capable of alleviating the enhanced local inflammation reaction of renal tissue under hyperglycemia state with the reduction of urinary ICAM-1 excretion.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/urine , Intercellular Adhesion Molecule-1/urine , Adult , Blood Glucose/metabolism , Creatinine/urine , Female , Glycated Hemoglobin/metabolism , Humans , Insulin/therapeutic use , Male , Middle Aged
16.
Ren Fail ; 30(7): 675-84, 2008.
Article in English | MEDLINE | ID: mdl-18704815

ABSTRACT

INTRODUCTION: In order to monitor acute renal failure, intensive care patients were examined, and routine as well as specialized parameters were compared. MATERIALS AND METHODS: Thirty-three patients at the Surgical Intensive Care Unit (ICU) were examined daily over the entire period for which they stayed in the ICU. The patients were retrospectively classified as being either with or without acute renal failure. Group 1 consisted of 22 patients who resided in the ICU for 11-15 (median 14) days without ARF. Group 2 consisted of 11 patients who developed an ARF during their stay of 13-18 (median 16) days in the ICU. In addition to the routine parameters of diuresis, serum creatinine/urea, and clearance of creatinine, specialized parameters for kidney function, including the excretion rates of alpha1-microglobulin, N-acetyl-beta-D-glucosaminidase, and total protein, were compared with the excretion rate of soluble ICAM-1 and sE-Selectin. RESULTS: Diuresis, serum creatinine, urea, and enzyme elimination were pathological among patients with ARF. Already on the day of admission, raised elimination rates of sICAM-1 were found in the urine of patients who had developed an ARF. While high values were still shown upon discharge, levels kept falling among patients without ARF. Clearly raised values were also shown for sE-Selectin compared to patients without ARF. CONCLUSIONS: sICAM-1 and sE-Selectin as supplementary parameters indicating renal function revealed early signs of kidney damage. These parameters may play a major role in the development of novel therapeutic approaches for ARF (antibodies against ICAM-1 or sE-Selectin).


Subject(s)
Acute Kidney Injury/blood , E-Selectin/urine , Intercellular Adhesion Molecule-1/urine , Acute Kidney Injury/diagnosis , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Adult , Aged , Biomarkers/urine , Case-Control Studies , Disease Progression , Evaluation Studies as Topic , Female , Follow-Up Studies , Humans , Intensive Care Units , Kidney Function Tests , Male , Middle Aged , Monitoring, Physiologic/methods , Probability , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Survival Rate , Treatment Outcome
17.
Am J Nephrol ; 28(1): 83-90, 2008.
Article in English | MEDLINE | ID: mdl-17914249

ABSTRACT

BACKGROUND/AIM: Steroid-resistant nephrotic syndrome (SRNS) has been associated with activation of TGF-beta(1) and progression to chronic kidney disease. Steroid-sensitive nephrotic syndrome (SSNS) has been associated with activation of T-cells and favorable outcome. Our objective was to distinguish SRNS from SSNS and focal segmental glomerulosclerosis (FSGS) from minimal change disease (MCD) on the basis of urinary cytokine profile. METHOD: We used a high-throughput cytokine array. ICAM-1 and TGF-beta(1) in urine and kidney tissue were evaluated by ELISA and immunohistochemistry (IHC), respectively. RESULTS: Age, gender, race, body mass index, and glomerular filtration rate were similar among groups. There were no statistically significant differences between SRNS (n = 12) and SSNS (n = 12) in regard to the presence of hypertension, treatment with ACE inhibitors, and renal histology. Arrays detected a 1- to 5.5-fold increase in urinary cytokine expression in subjects with idiopathic nephrotic syndrome (INS) as compared to controls. Using ELISA, urinary excretion of ICAM-1 was significantly higher in INS subjects than in controls (control group, n = 12; p = 0.005), but it did not differentiate SRNS from SSNS, or FSGS from MCD. IHC failed to reveal differences in renal tissue expression of ICAM-1 among controls, SRNS and SSNS. There were no significant differences among controls, and patients with SRNS and SSNS in the urinary excretion of TGF-beta(1) (p = 0.21). However, urinary TGF-beta(1) levels were significantly higher in FSGS than in MCD (p = 0.03), and IHC showed increased immunoreactivity in FSGS. CONCLUSION: Our data indicate that urinary TGF-beta(1) was able to differentiate between FSGS and MCD but was not a biomarker of steroid responsiveness.


Subject(s)
Biomarkers/urine , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/urine , Steroids/therapeutic use , Transforming Growth Factor beta1/urine , Adolescent , Child , Collagen Type IV/metabolism , Diagnosis, Differential , Drug Resistance , Female , Glomerulosclerosis, Focal Segmental/drug therapy , Glomerulosclerosis, Focal Segmental/urine , Humans , Intercellular Adhesion Molecule-1/urine , Male , Nephrosis, Lipoid/drug therapy , Nephrosis, Lipoid/urine , Protein Array Analysis
18.
J Endocrinol Invest ; 31(12): 1069-74, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19246972

ABSTRACT

OBJECTIVE: To observe the effect of rosiglitazone on serum intercellular adhesion molecule-1 (SICAM-1) level, urinary excretion of ICAM-1, and renal expression of ICAM-1, and investigate its possible renoprotective mechanisms in diabetic rats. METHOD: Twenty-four Wistar Rats were divided into 3 groups: non-diabetic control rats (group A, no.=8), streptozotocin-induced diabetic rats (group B, no.=8), and diabetic rats treated with rosiglitazone (group C, no.=8). Rats in group C were treated with rosiglitazone (5 mg x kg(-1) x d(-1)) 1 week after the establishment of diabetic model, group A and B were treated with corresponding sodium chloride. Peripheral blood glucose was tested weekly. Glycosylated hemoglobin (HbA1c) and SICAM-1 as well as urinary albumin excretion rate (UAER), urinary retinol binding-protein (URBP) excretion rate, and urinary ICAM-1 (UICAM- 1) excretion rate were tested at the 8th week, and the renal tissues of all rats were obtained for evaluating kidney/body weight ratio, observing pathologic change via electron microscope, and for examining the expression of ICAM-1 mRNA by reverse transcriptase-PCR. RESULTS: At the 8th week, the blood glucose, HbA1c levels, UAER, URBP excretion rate, kidney/body weight ratio and serum, urinary ICAM-1 levels all increased significantly in group B and group C in comparison with group A; however, the above-mentioned parameters in group C (except the blood glucose and HbA1c levels) were much lower than those in group B. In addition, both SICAM-1 and UICAM-1 were highly correlated with the UAER, URBP level, and kidney/body weight ratio in all rats; renal pathological lesions observed by electron microscope in group C were much lighter than those of group B; compared with group A, the expression of ICAM-1 mRNA was markedly up-regulated in group B and group C, and rosiglitazone was able to decrease the expression of ICAM-1 mRNA in the renal tissue. CONCLUSION: Rosiglitazone could definitely protect against the renal injury of diabetic rats, which may be partly associated with decreasing the expression of ICAM-1 in the renal tissue, reducing ICAM-1 productions in both serum and urine.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Intercellular Adhesion Molecule-1/genetics , Kidney/drug effects , Streptozocin , Thiazolidinediones/therapeutic use , Animals , Cytoprotection/drug effects , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/blood , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Diabetic Nephropathies/prevention & control , Down-Regulation/drug effects , Drug Evaluation, Preclinical , Gene Expression Regulation/drug effects , Hypoglycemic Agents/pharmacology , Intercellular Adhesion Molecule-1/blood , Intercellular Adhesion Molecule-1/metabolism , Intercellular Adhesion Molecule-1/urine , Kidney/metabolism , Male , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Rats , Rats, Wistar , Rosiglitazone , Thiazolidinediones/pharmacology
19.
Biocell ; 31(1): 1-12, 2007.
Article in English | MEDLINE | ID: mdl-17665634

ABSTRACT

Congenital obstructive nephropathy is the primary cause of end-stage renal disease in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. Obstructive uropathy effects -decline in the plasmatic renal flow and glomerular filtration rate, interstitial infiltrate of leukocytes, significant decrease of the urine concentration, loss of the capacity to concentrate urine as well as fibrosis and apoptosis- are a consequence of a variety of factors that work in complex ways and are still not fully understood. Mediators as angiotensin II, transforming growth factor-beta (TGF-beta) and nitric oxide (NO) have been implicated in congenital obstructive nephropathy. The renin-angiotensin system is regulated in different ways, affecting both renal structure and function, and that it in turn depends upon the duration of the obstruction. On the other hand, the role of nitric oxide in renal injury remains somewhat controversial due to the fact that it can exert opposite effects such as cytoprotective and prooxidant / proapoptotic efects as well as proinflammatory and anti-inflammatory effects. In addition, reactive oxidative species (ROS) might contribute to the progression of renal disease. During unilateral ureteral obstruction induced uncoordinated and aberrant growth may lead to the loss of cellular phenotype and apoptosis. Promoting inflammatory responses, the oxidizers can regulate the adherence of certain molecules and proinflammatory mediators, transcription factors and fibrogenic cytokines, that are clearly involved in the progression of renal disease. The congenital obstructive nephropathy is characterized by tubular atrophy, cellular proliferation, apoptosis and fibrosis; immature kidney is more susceptible than adult kidney to showing the above mentioned alterations. Apoptosis seems to be the principal mechanism that leads to tubular atrophy during the neonatal unilateral ureteral obstruction (UUO). Considering the significant role of the apoptosis in UUO, we believe of big interest the study of the regulatory factors of apoptosis in the renal obstruction neonatal. The complex biochemical and molecular events during the development, maintenance and progression of the renal injury in unilateral ureteral obstruction require further major studies to better understand the alterations mentioned above.


Subject(s)
Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/pathology , Ureteral Obstruction/physiopathology , Adult , Angiotensin II/metabolism , Angiotensin II/urine , Animals , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/urine , Biomarkers/metabolism , Child , Humans , Intercellular Adhesion Molecule-1/metabolism , Intercellular Adhesion Molecule-1/urine , Kidney Failure, Chronic/urine , Nitric Oxide/metabolism , Nitric Oxide/urine , Oxidative Stress , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/urine , Renin/metabolism , Renin/urine , Ureteral Obstruction/metabolism , Ureteral Obstruction/urine
20.
Biocell ; 31(1): 1-12, abr. 2007. ilus, graf
Article in English | LILACS | ID: lil-491532

ABSTRACT

Congenital obstructive nephropathy is the primary cause of end-stage renal disease in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. Obstructive uropathy effects -decline in the plasmatic renal flow and glomerular filtration rate, interstitial infiltrate of leukocytes, significant decrease of the urine concentration, loss of the capacity to concentrate urine as well as fibrosis and apoptosis- are a consequence of a variety of factors that work in complex ways and are still not fully understood. Mediators as angiotensin II, transforming growth factor-beta(TGF-beta) and nitric oxide (NO) have been implicated in congenital obstructive nephropathy. The renin-angiotensin system is regulated in different ways, affecting both renal structure and function, and that it in turn depends upon the duration of the obstruction. On the other hand, the role of nitric oxide in renal injury remains somewhat controversial due to the fact that it can exert opposite effects such as cytoprotective and prooxidant / proapoptotic efects as well as proinflammatory and anti-inflammatory effects. In addition, reactive oxidative species (ROS) might contribute to the progression of renal disease. During unilateral ureteral obstruction induced uncoordinated and aberrant growth may lead to the loss of cellular phenotype and apoptosis. Promoting inflammatory responses, the oxidizers can regulate the adherence of certain molecules and proinflammatory mediators, transcription factors and fibrogenic cytokines, that are clearly involved in the progression of renal disease. The congenital obstructive nephropathy is characterized by tubular atrophy, cellular proliferation, apoptosis and fibrosis; immature kidney is more susceptible than adult kidney to showing the above mentioned alterations.


Subject(s)
Humans , Animals , Child , Adult , Angiotensin II/metabolism , Angiotensin II/urine , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/pathology , Intercellular Adhesion Molecule-1/metabolism , Intercellular Adhesion Molecule-1/urine , Nitric Oxide/metabolism , Nitric Oxide/urine , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/urine , Apoptosis , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/urine , Biomarkers/metabolism , Oxidative Stress , Ureteral Obstruction/physiopathology , Ureteral Obstruction/metabolism , Ureteral Obstruction/urine
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