Urinary Monocyte Chemoattractant Protein-1 Levels Research Articles

Relationships of Thickness of Perirenal Fat with Urinary Levels of MCP-1 and NGAL in Patients with Hypertension.

We conducted a study to determine the relationships between perirenal fat (PRF) thickness and urinary levels of monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) in patients with hypertension (HTN). In 338 HTN patients (aged 63.51±12.3 on average), MCP-1 and NGAL levels were studied using enzyme-linked immunosorbent assay (ELISA). To measure PRF thickness, all patients underwent CT scans. We considered PRF thickness ≥1.91 cm as the diagnostic threshold for perirenal obesity. Patients with excessive PRF thickness exhibited significantly lower levels of MCP-1 and NGAL compared with those with PRF thickness ≥1.91 cm: 0.98 pg/mL (interquartile range, 0.21 to 2.05) vs. 2.35 pg/mL (0.37 to 5.22) for MCP-1 and 50.0 pg/mL (48.9 to 67.8) vs. 98.3 pg/mL (68.4 to 187.1) for NGAL. We found a relationship of PRF thickness with both MCP-1 (r=0.46, P<0.05) and NGAL (r=0.53, P<0.05), the levels of which were significantly different in patients with first- and third-stage chronic kidney disease: 0.33 pg/mL (0.21 to 1.35) vs. 4.47 pg/mL (0.23 to 10.81); 50.0 pg/mL (49.4 to 85.5) vs. 126.45 pg/mL (57.5 to 205.15), respectively (P=0.04). Patients with metabolically healthy obesity (MHO) had significantly lower MCP-1 levels than those with metabolically unhealthy obesity (MUHO): 0.65 pg/mL (0.21 to 2.15) vs. 3.28 pg/mL (2.05 to 5.22) (P=0.014). MHO patients showed significantly lower NGAL levels than MUHO patients: 50.0 pg/mL (49.4 to 62.2) vs. 98.3 pg/mL (50.0 to 174.8) (P=0.04). Multiple linear regression analysis revealed significant relationships of MCP-1 with PRF thickness (β±standard error, 0.41±0.15; P<0.001) and smoking (0.26±0.13; P=0.01) and of NGAL with age (0.45±0.16; P<0.01) and PRF thickness (0.49±0.15; P<0.001). We identified higher concentrations of renal fibrosis markers in patients with perirenal and metabolically unhealthy obesity as well as a link between PRF thickness and MCP-1 and NGAL levels in urine.

Combination of urinary biomarkers and machine-learning models provided a higher predictive accuracy to predict long-term treatment outcomes of patients with interstitial cystitis/bladder pain syndrome.

To identify predictive factors for satisfactory treatment outcome of the patients with IC/BPS using urine biomarkers and machine-learning models. The IC/BPS patients were prospectively enrolled and provide urine samples. The targeted analytes included inflammatory cytokines, neurotrophins, and oxidative stress biomarkers. The patients with overall subjective symptom improvement of ≥ 50% were considered to have satisfactory results. Binary logistic regression, receiver-operating characteristic (ROC) curve, machine-learning decision tree, and random forest models were used to analyze urinary biomarkers to predict satisfactory results. Altogether, 57.4% of the 291 IC/BPS patients obtained satisfactory results. The patients with satisfactory results had lower levels of baseline urinary inflammatory cytokines and oxidative biomarkers than patients without satisfying results, including interleukin-6, monocyte chemoattractant protein-1 (MCP-1), C-X-C motif chemokine 10 (CXCL10), oxidative stress biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHDG), 8-isoprostane, and total antioxidant capacity (TAC). Logistic regression and multivariable analysis revealed that lower levels of urinary CXCL10, MCP-1, 8-OHDG, and 8-isoprostane were independent factors. The ROC curve revealed that MCP-1 level had best area under curve (AUC: 0.797). In machine-learning decision tree model, combination of urinary C-C motif chemokine 5, 8-isoprostane, TAC, MCP-1, and 8-OHDG could predict satisfactory results (accuracy: 0.81). The random forest model revealed that urinary 8-isoprostance, MCP-1, and 8-OHDG levels had the most important influence on accuracy. Machine learning decision tree model provided a higher accuracy for predicting treatment outcome of patients with IC/BPS than logistic regression, and levels of 8-isoprostance, MCP-1, and 8-OHDG had the most important influence on accuracy.

Effect of Sleeve Gastrectomy Versus One Anastomosis Gastric Bypass on Postoperative Renal Function and the Urinary Monocyte Chemoattractant Protein-1 (MCP-1) Level

IntroductionBariatric surgery has been the most effective treatment modality for morbid obesity that reduces associated comorbidities and improves quality of life. This study aims at evaluating and comparing the impact of two types of bariatric surgery—laparoscopic sleeve gastrectomy (LSG) and one anastomosis gastric bypass (OAGB)—on renal functions and urinary monocyte chemoattractant protein-1 (MPC-1) levels in morbidly obese patients 3 months after surgery.MethodsThis is a prospective study of 40 morbidly obese patients who underwent bariatric surgery. Two types of bariatric surgery were done—laparoscopic sleeve gastrectomy (LSG) (26 patients) and laparoscopic one anastomosis gastric bypass (OAGB) (14 patients). The outcomes of the two procedures were compared in terms of renal function parameters and the level of urinary MCP-1.ResultsThere were no statistically significant differences in the mean postoperative urinary MCP-1 (73.53 ± 21.25, 75.43 ± 26.17, P > 0.5), microalbuminuria (8.83 ± 6.26, 10.02 ± 8.6, P > 0.05), urinary creatinine (109.21 ± 43.22, 99.19 ± 48.65, P > 0.05), MCP1/Cr ratio (0.78 ± 0.36, 1.01 ± 0.70, P > 0.05), eGFR (100.32 ± 9.54, 104.39 ± 9.54, P > 0.05) in the cases who had either LSG operation or OAGB operation.ConclusionBariatric surgery improves all indicators of kidney malfunction and reduces the level of urinary MCP-1. Both laparoscopic sleeve gastrectomy (LSG) and laparoscopic one anastomosis gastric bypass (OAGB) cause similar improvement of the renal function and reduction of urinary MCP-1 level.Graphical

The role of urinary biomarker monocyte chemoattractant protein (MCP-1) in correlation with different histopathological classes of lupus nephritis in Egyptian patients

Lupus nephritis (LN) affects almost two-thirds of systemic lupus erythematosus (SLE) patients. Renal biopsy is the gold standard for the diagnosis of LN. However, repeated biopsies are not always performed in clinical practice, and they carry some risk. Therefore, minimally invasive techniques, as urinary biomarkers, are promising tools for the diagnosis and monitoring of SLE. Previous studies evaluated urinary monocyte chemoattractant protein-1 (MCP-1) in patients with SLE, reported higher levels of urinary MCP-1 in patients with active LN than non-active LN. Other studies reported higher levels of urinary MCP-1 in LN patients with proliferative forms (III and IV). This study aimed to evaluate urinary MCP-1 as a noninvasive diagnostic biomarker tool for LN, and to determine its association with different LN histopathological stages and chronicity indices. The study included 40 SLE patients with biopsy-proven LN class II, III, IV or V, and 20 patients with inactive LN as a control group. In LN active patients, the mean creatinine was 1.71 ± 0.55 mg/dl, and 0.84 ± 0.10 mg/dl in the control group. The mean MCP-1 level was 618.4 ± 294.2 ng/l in active LN patients and 120.05 ± 87.53 ng/l in inactive LN patients. The receiver operating characteristic (ROC) curve analysis indicated a better diagnostic performance of MCP-1 than conventional biomarkers. At area under the curve of 0.990, the best cut-off level was &gt;245 ng/L (sensitivity 97.5 %, Specificity 95 %). In conclusion, urinary MCP-1 distinguished active LN from inactive renal disease. It can be proposed as a good noninvasive diagnostic biomarker with a high sensitivity and specificity for detection of LN activity.

The Role of Monocyte Chemoattractant Protein-1 (MCP-1) in Diabetic Kidney Disease

Monocyte chemoattractant protein-1 plays an important role in kidney disease. In several studies, the role of MCP-1 as a urine biomarker has been extensively studied. In many kidney diseases, there are elevated levels of MCP-1 in the kidney tissue and this is an important cause of monocyte infiltration in the pathogenesis of kidney damage. Elevated urinary MCP-1 levels have been able to predict outcome in proliferative kidney diseases such as lupus nephritis. However, in several studies it was also found that there was an increase in MCP-1 in diabetic kidney disease. Macrophages have even appeared early in diabetic kidney disease and are associated with the progression of kidney disease. Urinary MCP-1 levels are related to the degree of leukocyte infiltration in the tubulointerstitial. This supports inflammatory factors as part of the pathogenesis of diabetic kidney disease.

Intrarenal renin–angiotensin system activation and macrophage infiltrations in pediatric chronic glomerulonephritis

BackgroundThe current study tested the hypothesis that urinary angiotensinogen (UAGT) and urinary monocyte chemoattractant protein-1 (UMCP-1) levels provide a specific index of intrarenal renin–angiotensin system (RAS) status and the degree of infiltration of macrophages associated with RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis.MethodsWe measured baseline UAGT and UMCP-1 levels to examine the correlation between glomerular injury in 48 pediatric chronic glomerulonephritis patients before treatment. Furthermore, we performed immunohistochemical analysis of angiotensinogen (AGT) and CD68 in 27 pediatric chronic glomerulonephritis patients treated with RAS blockades and immunosuppressants for 2 years. Finally, we examined the effects of angiotensin II (Ang II) on monocyte chemoattractant protein-1 (MCP-1) expression in cultured human mesangial cells (MCs).ResultsBaseline UAGT and UMCP-1 levels positively correlated with urinary protein levels, scores for mesangial hypercellularity, rate of crescentic formation, and expression levels of AGT and CD68 in renal tissues (p < 0.05). UAGT and UMCP-1 levels were significantly decreased after RAS blockade and immunosuppressant treatment (p < 0.01), which was accompanied by AGT and CD68 (p < 0.01), as well as the magnitude of glomerular injury. Cultured human MCs showed increased MCP-1 messenger ribonucleic acid and protein levels after Ang II treatment (p < 0.01).ConclusionsThe data indicates that UAGT and UMCP-1 are useful biomarkers of the degree of glomerular injury during RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis.

Ethnic differences in urinary monocyte chemoattractant protein-1 and heparanase-1 levels in individuals with type 2 diabetes: the HELIUS study

IntroductionWe aimed to investigate ethnic differences in two urinary inflammatory markers in participants with type 2 diabetes mellitus (T2DM).Research design and methodsWe included 55 Dutch, 127 South-Asian Surinamese, 92 African...

Usefulness of Urinary Biomarkers for Assessing Bladder Condition and Histopathology in Patients with Interstitial Cystitis/Bladder Pain Syndrome.

This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We retrospectively enrolled 315 patients (267 women and 48 men) diagnosed with IC/BPS and 30 controls. Data on clinical and urodynamic characteristics (visual analog scale (VAS) score and bladder capacity) and cystoscopic hydrodistention findings (Hunner’s lesion, glomerulation grade, and maximal bladder capacity (MBC)) were recorded. Urine samples were utilized to assay inflammatory, neurogenic, and oxidative stress biomarkers, including interleukin (IL)-8, C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin, IL-6, macrophage inflammatory protein 1 beta (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-isoproatane, and total antioxidant capacity. Further, specific histopathological findings were identified via bladder biopsy. The associations between urinary biomarker levels and bladder conditions and histopathological findings were evaluated. The results reveal that patients with IC/BPS had significantly higher urinary MCP-1, eotaxin, TNF-α, PGE2, 8-OHdG, and 8-isoprostane levels than controls. Patients with Hunner’s IC (HIC) had significantly higher IL-8, CXCL10, BDNF, eotaxin, IL-6, MIP-1β, and RANTES levels than those with non-Hunner’s IC (NHIC). Patients with NHIC who had an MBC of ≤760 mL had significantly high urinary CXCL10, MCP-1, eotaxin, IL-6, MIP-1β, RANTES, PGE2, and 8-isoprostane levels and total antioxidant capacity. Patients with NHIC who had a higher glomerulation grade had significantly high urinary MCP-1, IL-6, RANTES, 8-OHdG, and 8-isoprostane levels. A significant association was observed between urinary biomarkers and glomerulation grade, MBC, VAS score, and bladder sensation. However, bladder-specific histopathological findings were not well correlated with urinary biomarker levels. The urinary biomarker levels can be useful for identifying HIC and different NHIC subtypes. Higher urinary inflammatory and oxidative stress biomarker levels are associated with IC/BPS. Most urinary biomarkers are not correlated with specific bladder histopathological findings; nevertheless, they are more important in the assessment of bladder condition than bladder histopathology.

Clopidogrel delays and can reverse diabetic nephropathy pathogenesis in type 2 diabetic db/db mice.

BACKGROUNDDiabetic nephropathy (DN) is the principal cause of end-stage renal disease. Previous studies have shown that clopidogrel can prevent the early progression of renal injury.AIMTo elucidate whether clopidogrel is beneficial against DN by using a db/db mouse model.METHODS db/db mice with a higher urinary albumin/creatinine ratio (ACR) relative to age- and sex-matched wild-type control mice were randomly allocated to clopidogrel and vehicle treatment groups. Clopidogrel was administered at doses of 5, 10, and 20 mg/kg by gavage for 12 wk. Body mass, blood glucose level, and urinary creatinine and albumin concentrations in each group were measured before and after the intervention. Renal fibrosis was evaluated using periodic acid-Schiff and Masson’s trichrome staining. The renal protein expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and F4/80 was assessed using immunohistochemistry. Urinary TNF-α, monocyte chemoattractant protein-1 (MCP-1), and IL-6 levels were analyzed using enzyme-linked immunosorbent assay; TNF-α and IL-1β mRNA expression was measured using real-time quantitative polymerase chain reaction. The protein expression of fibronectin (FN) and collagen I was assessed using immunohistochemistry.RESULTSClopidogrel treatment did not affect the body mass or blood glucose level of the db/db mice; however, it increased bleeding time and reduced urinary ACR in a dose-dependent manner. Immunohistochemical staining revealed an amelioration of renal fibrosis, significantly lower deposition of FN and collagen I, and significantly lower expression of the proinflammatory cytokines TNF-α and IL-1β and lower levels of urinary TNF-α and MCP-1 in the clopidogrel-treated db/db mice (P < 0.05). Furthermore, clopidogrel significantly reduced macrophage infiltration into the glomeruli of the db/db mice.CONCLUSIONClopidogrel significantly reduced renal collagen deposition and fibrosis and prevented renal dysfunction in db/db mice, most likely through inhibition of renal macrophage infiltration and the associated inflammation.

MO176: Study of Urinary Monocyte Chemoattractant Protein-1(MCP-1) Level in Morbidly Obese Patients before and After Bariatric Surgeries and its Relation to Renal Function

Abstract BACKGROUND AND AIMS To assess the level of renal inflammatory marker monocyte chemoattractant protein -1(MCP-1), measure the urinary MCP to urinary creatinine concentration ratio in morbidly obese patients before and after bariatric surgeries. To study if there any possible relation between the MCP1 levels and renal function before and after surgery. METHOD This prospective study of 40 morbidly obese patients undergoing bariatric surgery was recruited in the study in the interval between October 2018 and July 2019. Evaluate the level of MCP-1, urinary creatinine, urinary albumin, glomerular filtration rate, body weight, body mass index, CRP, serum albumin, blood pressure and lipid profile before and after 3 months of bariatric surgeries. RESULTS The mean urinary level of MCP1 preoperative was 105.19 ± 15.25 pg/mL (range between 75.41 and 131.67) and this level was decreased postoperatively to 74.20 ± 22.77 (range between 30.5 and 114.4) with high statistically significant difference (P &amp;lt; .001). While urinary MCP1/creatinine ratio, bariatric surgery significantly reduced the mean of urinary MCP1/creatinine ratios from 2.08 ± 1.43 to 0.86 ± 0.51 (P &amp;lt; 0.001). Significant improvement of blood pressure, CRP, lipid profile and body mass index after bariatric surgeries. CONCLUSION We reported that urinary MCP-1 levels following bariatric surgery can be used as potential marker to the ongoing renal inflammatory process.

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and Selected Cytokines—Potential Biomarkers in Children with Solitary Functioning Kidney

This study was performed to explore serum tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its dependent cytokines urinary excretion: monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted chemokine (RANTES) with their relation to the kidney function parameters in children with solitary functioning kidney (SFK). The study included 80 children and adolescents (median age 9.75 year) with congenital and acquired (after surgical removal) SFK. Serum TWEAK and urinary MCP-1 and RANTES levels were significantly higher in SFK patients (p < 0.05). The serum TWEAK was positively related to serum creatinine (r = 0.356; p < 0.001). Moreover, in SFK the receiver operating characteristic analyses revealed good diagnostic profile for serum TWEAK with AUC (Area Under The Curve)—0.853, uRANTES—0.757, and for RANTES/cr.: AUC—0.816. Analysis carried out to identify children with impaired renal function (albuminuria and/or decreased estimated glomerular filtration rate < 90 mL/min/1.73 m2 and/or hypertension) showed good profile for TWEAK (AUC—0.79) and quite good profile for uRANTES and RANTES/cr. (AUC 0.66 and 0.631, respectively). This is the first study investigating serum TWEAK and urinary excretion of MCP-1 and RANTES together in children with SFK. Obtained results indicate that TWEAK and RANTES may serve as potential markers of renal impairment.

Exploring molecular pathology of chronic kidney disease in systemic sclerosis by analysis of urinary and serum proteins.

Objective.Renal involvement is common in systemic sclerosis (scleroderma; SSc) and includes chronic kidney disease (CKD). We have performed analysis of urinary proteins to gain insight into local molecular pathology of CKD in SSc and identify candidate markers for use in clinical trials.Methods.To evaluate urinary proteins that might specifically reflect SSc-related CKD, patients were recruited with confirmed SSc and stratified for the presence or absence of CKD. Controls included patients with CKD and no SSc, in addition to healthy volunteers. Candidate markers were measured in serum and urine by multiplex immunoassay testing for IL6, IL18, TNF-α, monocyte chemoattractant protein 1 (MCP1), monocyte chemoattractant protein 3 (MCP3), VEGF and the soluble adhesion molecules vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Results.One hundred and two subjects were examined, including patients with SSc with no evidence of CKD (n = 40), SSc with CKD (n = 39), non-SSc CKD (n = 11) and healthy volunteers (n = 12). Urinary levels of IL6, MCP1, TNF-α, MCP3, IL18 and ICAM-1 were elevated in SSc patients compared with healthy controls. The most significant differences were for MCP1 and ICAM-1 (both P < 0.0001), and these analytes also showed the most significant differences between groups overall (P = 0.003 for MCP1 and P < 0.0001 for ICAM-1). These markers showed a trend (MCP1, P = 0.0868) or a significant difference (ICAM-1, P = 0.0134) between SSc–CKD and SSc with normal renal function.Conclusion.Urinary levels of candidate molecular markers appear to reflect SSc–CKD more than serum markers. MCP1 and ICAM-1 are promising molecular markers for SSc–CKD and might be potential biomarkers of SSc renal involvement. This might be explored in future prospective analyses.

Potential Role of Monocyte Chemoattractant Protein-1 in Monitoring Disease Progression and Response to Treatment in Overactive Bladder Patients.

PurposeTo compare urinary levels of monocyte chemoattractant protein-1 (MCP-1), an inflammatory cytokine, in healthy controls and overactive bladder (OAB) patients, to correlate changes in urinary MCP-1 with OAB treatment response and symptom severity, and to study the diagnostic potential of MCP-1 for OAB, as well as the efficacy of MCP-1 as a potential biomarker for different phenotypes of OAB.MethodsWe used enzyme-linked immunosorbent assay to measure normalized urinary MCP-1 levels in 56 individuals (43 OAB patients and 13 controls). We assessed the OAB patients at 3 visits with 2 validated symptom severity questionnaires (OAB-V8 and Patient Perception of Bladder Condition).ResultsThe mean pretreatment urinary MCP-1 level at visit 1 (229.2-pg/mg creatinine) was significantly greater than the MCP-1 levels at visit 3 in both the treatment (107.0-pg/mg creatinine) (P<0.001) and control (52.35-pg/mg creatinine) groups (P<0.001). Average OAB symptom severity decreased significantly from visit 1 (baseline) to visits 2 (4 weeks) and 3 (12–14 weeks) and was significantly correlated with urinary MCP-1 levels. Urinary MCP-1 levels dropped significantly (P=0.002) posttreatment in patients whose symptom severity improved by >30%, whereas nonresponders displayed no significant MCP-1 decrease (P=0.164). The receiver operating characteristic analysis of the OAB visit 1 and control groups produced an area under the curve of 0.891. We found no significant differences in sex, race, or age between the OAB and control groups.ConclusionsMCP-1 levels differed significantly between the control and OAB groups and were closely correlated with symptom severity and treatment response. The good diagnostic accuracy of MCP-1 for OAB suggests the potential usage of MCP-1 for OAB diagnosis. The varying response of urinary MCP-1 levels to treatment may indicate at least 2 potential phenotypes of OAB. MCP-1, in combination with other biomarkers and symptom severity questionnaires, could potentially aid in developing a patient-centered OAB treatment approach.

Urinary levels of ceruloplasmin and monocyte chemoattractant protein-1 correlate with extra-capillary proliferation and chronic damage in patients with lupus nephritis.

There are few studies of urinary biomarkers and histopathologic features in lupus nephritis (LN). The aim was to analyze the correlation between a wide panel of urinary biomarkers and serum concentrations of anti C1q antibodies with histological items of activity and chronicity on kidney biopsy in LN patients. Patients with systemic lupus erythematosus (SLE) according to American College of Rheumatology (ACR) criteria were included. LN diagnosis was based on ACR criteria. Histologic features of activity and chronicity indices were analyzed according to the Austin classification. Serum Anti C1q levels were determined by commercial ELISA. Urinary levels of transferrin, ceruloplasmin (CP), VCAM-1, TWEAK, monocyte chemoattractant protein-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), and alpha-1-acid glycoprotein were measured by commercial ELISA. We included 120 SLE patients (81% female, mean age 33.1 ± 9.3years, 59.4% Mestizo, 37.8% Afro-Latin American): 64% had LN. Kidney biopsy was performed in 55 patients, but only 37 were made in our center. Anti C1q antibodies were associated with endocapillary proliferation. In patients with cellular crescents, urinary concentrations of CP were significantly higher. In patients with a chronicity index (CI) ≥ 4, fibrous crescents, tubular atrophy, and interstitial fibrosis, urinary MCP-1 levels were higher. In SLE patients, serum anti C1q antibodies and urinary CP were associated with activity on kidney biopsy and MCP-1 with chronic damage. This panel of biomarkers could be validated in larger, multi-ethnic population as a complementary tool for better stratification of LN patients. Key Points • Urinary biomarkers are complementary useful tools for the assessment of SLE patients. • Urinary levels of CP correlated with activity findings on kidney biopsy in LN patients. • Urinary levels of MCP-1 correlated with chronic damage, especially with fibrous crescents, tubular atrophy, and interstitial fibrosis.

Diagnostic potential of urinary monocyte chemoattractant protein-1 for Alzheimer's disease and amnestic mild cognitive impairment.

The chemokine monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether urinary MCP-1 can distinguish patients with AD, patients with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) subjects. A total of 754 participants, including 97 patients with AD, 50 patients with aMCI and 84 age- and sex-matched CN controls as well as a cohort of 523 CN subjects of different ages, were enrolled from five hospitals located in different areas of China. Urinary MCP-1 levels were determined using enzyme-linked immunosorbent assays. The correlations between urinary MCP-1 levels and cognition test scores or age were analysed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. In the cohort of CN subjects of different ages, urinary MCP-1 levels increased with ageing and were correlated with age. The urinary MCP-1 levels were higher in females than in males. In the cohort composed of patients with AD, aMCI and age- and sex-matched CN controls, urinary MCP-1 levels were significantly higher in patients with AD and aMCI than in CN controls. There were no differences in urine MCP-1 levels between the AD group and the aMCI group. The urinary MCP-1 levels were correlated with the Mini-Mental State Examination scores and age, and were able to differentiate patients with AD and aMCI from CN subjects. Urinary MCP-1 is a potential biomarker for the diagnosis of AD and aMCI.

Clinical Significance of Urinary Monocyte Chemoattractant Protein-1 (uMCP-1) and TNF-Alfa in Indian Type 2 Diabetic Patients at Different Stages of Diabetic Nephropathy

Introduction: TNF alfa and Monocyte Chemoattractant Protein-1 (MCP-1) are inflammatory markers upregulated in diabetic nephropathy. This study aims to find the levels of urinary MCP-1 (uMCP-1) and serum TNF alfa levels at different stages of diabetic nephropathy and to see its correlation with UACR(Urinary Albumin Cdeatinine Ratio) in Indian type2 diabetic subjects Methods: Consecutive Patients of Type 2 Diabetes Mellitus (DM) with or without microalbuminuria attending SCB MEDICAL COLLEGE and HOSPITAL Medical OPDs in one year were recruited in this study.Patients were subjected to blood and urine investigations. Groups are Group 1 (control), Group 2 (diabetes with normoalbuminuria), Group 3 (diabetes with microalbuminuria), Group 4 (diabetes with macroalbuminuria). Diabetic Nephropathy were classified according to KIGDO staging. Anthropometric and biochemical details were recorded for all the subjects.UACR calculated by the formula which has been approved by National Kidney Disease Education Program. Urinary MCP-1 and TNF alfa levels were measured by using ELISA. Results: S.urea creatinine, Total cholesterol, TG, LDL, UACR, S.TNF alfa, UMCP1 levels are significantly high in diabetes with macroalbuminuria group (p = 0.01, 0.001, 0.013, 0.01, <0.01, <0.01, <0.01, 0.01 respectively). UACR is positively correlated with umcp1 (r= 0.413 , P=<0.01) and S.TNF alfa (r= 0.218, p=0.008). Increasing uMCP-1, S.TNF alfa levels with the progression of diabetic nephropathy indicating the extent of renal tubular and glomerular damage (p value 0.015,0.008 respectively.) Funding Statement: The authors stated: No funding has been allocated to this research work. Declaration of Interests: The authors declared: There is no conflict of interest. Ethics Approval Statement: This cross-sectional study has been approved by Ethical committee

Urinary Monocyte Chemoattractant Protein -1 as A Diagnostic Marker of Lupus Nephritis

Background: Lupus nephritis accounts for significant morbidity and mortality in patients with systemic lupus erythematosus (SLE). Many biomarkers for renal involvement in SLE have been suggested in Egyptian patients; one of them is Monocyte chemoattractant protein-1 (MCP-1) which is one of the key chemokines that have chemotactic effect for monocytes and macrophages to sites of inflammation and may share in the pathogenesis of lupus nephritis (LN). Aim: The study aimed at assessing the role of MCP-1 in the early diagnosis of lupus nephritis and to explore any correlation its levels with disease activity and renal status. Subjects and Methods: The study was done as a case-control study where 60 SLE patients with lupus nephritis (30 patients with active LN and 30 patients with inactive LN) in addition to 30 healthy volunteers as control group were enrolled in the study and MCP-1 levels was determined using ELISA technique. Results: Urinary MCP-1 levels in SLE studied patients’ groups were significantly higher than their level in the control group (p = 0.0001) and it was significantly higher in active LN than in non-active LN subgroups (P-value =0.0001). Conclusion: Urinary MCP-1 can be used as a marker for LN activity. Keywords: SLE, Lupus nephritis, MCP-1

Association between urinary biomarkers and disease progression in adults with autosomal dominant polycystic kidney disease.

BackgroundHeight-adjusted total kidney volume (htTKV) is considered as the best predictor of kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD), but its limited predictive capacity stresses the need to find new biomarkers of ADPKD progression. The aim of this study was to investigate urinary biomarkers of ADPKD progression.Methods This observational study included ADPKD patients, and two comparator groups of ischaemic and non-ischaemic kidney injury: benign nephroangiosclerosis patients and non-ischaemic chronic kidney disease (CKD) patients. Proteinuria, htTKV and urinary levels of molecules are associated with ischaemia and/or tubular injury. The slope of estimated glomerular filtration rate (eGFR) was used as a dependent variable in univariate and multivariate models of kidney function decline.ResultsThe study included 130 patients with ADPKD, 55 with nephroangiosclerosis and 40 with non-ischaemic CKD. All patients had increased urinary concentrations of biomarkers associated with tubular lesions (liver fatty acid-binding protein, kidney injury molecule-1, β2-microglobulin) and molecules overexpressed under ischaemic conditions [hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1)]. These biomarkers correlated positively with htTKV and negatively with the eGFR slope. htTKV was the single best predictor of the eGFR slope variability in univariate analyses. However, a multivariate model including urinary levels of β2-microglobulin, MCP-1 and VEGF improved the capacity to predict the decline of eGFR in ADPKD patients compared with htTKV alone.ConclusionsThe urinary levels of molecules associated with either renal ischaemia (VEGF and MCP-1) or tubular damage (β2-microglobulin) are associated with renal function deterioration in ADPKD patients, and are, therefore, candidates as biomarkers of ADPKD progression.

Characterisation of urinary monocyte chemoattractant protein 1: Potential biomarker for patients with overactive bladder

ABSTRACTObjective: To investigate urinary monocyte chemoattractant protein 1 (MCP-1) as a potential marker for idiopathic overactive bladder (OAB). This is a quantitative measurement of urinary MCP-1 to establish baseline normal values that could help in future index studies. Normalised urinary MCP-1 levels are measured in female patients with OAB and aged-matched controls. Severity of OAB symptoms is correlated to normalised urinary MCP-1 levels.Patients and methods: Urinary MCP-1 levels were measured in 29 female patients with OAB and 10 normal female controls. The patients with OAB were either newly diagnosed or off any OAB oral therapy for at least 2 weeks. OAB symptoms were assessed using validated OAB questionnaires. Urinary MCP-1 levels were measured using enzyme-linked immunosorbent assay and normalised by urinary creatinine (Cr) levels.Results: The baseline urinary MCP-1 levels in female patients with OAB were significantly higher than those of the controls, at a mean of 210.25 vs 48.02 pg/mg Cr (P < 0.001). Patients who had severe OAB bother symptoms had higher levels of urinary MCP-1 (r = 0.03), also patients with OAB-wet had higher levels of urinary MCP-1, at a mean (SEM) of 209.25 (30.5) vs OAB-dry 185.25 (10) pg/mg Cr (P < 0.001).Conclusion: Urinary MCP-1 levels were higher in female patients with idiopathic OAB. The close association of urinary MCP-1 and OAB bother severity symptoms and OAB-wet suggest that inflammation plays a major role in the pathophysiological mechanisms underlying the sensitisation of bladder afferent nerves. Establishing urinary MCP-1 levels in patients with OAB hopefully will help future studies to confirm the correlation as a baseline and changes with treatments.Abbreviations: BMI: body mass index; Cr: creatinine; MCP-1: monocyte chemoattractant protein 1; OAB: overactive bladder; OAB-q: Overactive Bladder Questionnaire; PPBC: Patient Perception of Bladder Condition; UI: urinary incontinence

Elevated urinary lipocalin-2, interleukin-6 and monocyte chemoattractant protein-1 levels in children with congenital ureteropelvic junction obstruction

In children with congenital ureteropelvic junction obstruction (UPJO), urinary biomarkers could assist in the diagnosis of renal damage or kidneys at risk for damage. Urinary levels of interleukin-6 (IL6), neutrophil gelatinase-associated lipocalin (LCN2), monocyte chemoattractant protein-1 (MCP1), and transforming growth factor-β1 (TGFB1) proteins have been correlated with renal damage in several contexts. Whether they might be useful non-invasive biomarkers of obstructive nephropathy due to unilateral and bilateral congenital UPJO was tested. A cohort study was performed at People's Hospital of Xinjiang Uygur Autonomous Region in China. Bladder urine samples from 17 patients with UPJO were obtained before surgical intervention and from 17 healthy age-matched controls. Levels of IL6, LCN2, MCP1, and TGFB1 were determined by enzyme-linked immunosorbent assay and normalized to urinary creatinine levels. Levels of urinary LCN2, MCP1, and IL6 were significantly elevated in the urine from individuals with UPJO compared with controls (P=0.0003, P=0.0003, and P=0.0073, respectively). Children with bilateral UPJO (n=5) showed significantly higher levels of IL6, LCN2, and MCP1 protein in their urine compared with controls or those with unilateral UPJO (n=12; P=0.007, P<0.0001, and P=0.0002, respectively). Combining LCN2 and MCP1 slightly improved biomarker performance. Urinary biomarkers could be used in obstructed patients to monitor for renal damage and might find particular utility on patients with bilateral UPJO. Monitoring urinary biomarkers and imaging features in untreated patients could provide insights into the natural history of renal damage due to obstruction and will be necessary to test their performance characteristics as biomarkers. Urinary levels of LCN2 and MCP1 protein are promising biomarkers monitoring children with UPJO, particularly in those with bilateral disease.