uMCP-1 Levels Research Articles

Immune checkpoint inhibitors induce acute interstitial nephritis in mice with increased urinary MCP1 and PD-1 glomerular expression

IntroductionImmune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2–5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients.MethodsTwenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression.ResultsCisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity.ConclusionsOnly mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker.

Silent Lupus Nephritis: Renal Histopathological Profile and Early Detection with Urinary Monocyte Chemotactic Protein 1.

ObjectiveLupus nephritis (LN) affects almost half of all individuals with systemic lupus erythematosus (SLE). Overt LN (OLN) symptoms might vary from asymptomatic microscopic hematuria to renal failure. However, when there are no clinical or laboratory indicators of renal involvement, some people with silent LN (SLN) may have pathological evidence of renal involvement identified by renal biopsy. Monocyte Chemotactic Protein 1 (MCP-1) is a chemotactic factor that promotes leukocyte migration to the kidney. MCP-1 urine levels (uMCP-1) have been demonstrated to be high in individuals with active LN. The purpose of this study was to discover the occurrence of SLN, as well as the possible variations between overt LN (OLN) and SLN across SLE patients based on the histopathological assessment, as well as the role of uMCP-1 in the early detection of SLN.MethodsAn overall of 144 patients with SLE were included in the current research. Patients were subsequently divided into two groups: individuals who did not have clinical evidence of LN (84 patients) and those with OLN (60 patients). All the patients were subjected to the following investigations: uMCP-1, erythrocyte sedimentation rate (ESR), complement C3 (C3), complement C4 (C4), creatinine, albumin/creatinine ratio (uACR), creatinine clearance, quantitative assessment of proteinuria by 24-hour urine proteinuria (24hr UP) and percutaneous renal biopsy.ResultsSixty patients from group I (71.4%) showed glomerular lesions on renal biopsy (SLN), and class II was the predominant class. uMCP-1 had a sensitivity of 95.2% and a specificity of 98% in the detection of SLN, and uMCP-1 values were markedly higher in patients with OLN in comparison to SLN.ConclusionThe actual frequency of SLN may be higher than expected. High levels of uMCP-1 may have warranted the early activity of LN. uMCP-1 can be used as a non-invasive, useful tool for the prediction of LN.

Urinary MCP-1 and TWEAK as non-invasive markers of disease activity and treatment response in patients with lupus nephritis in South Africa.

Treatment of patients with lupus nephritis (LN) requires judicious use of immunosuppression. Novel biomarkers may be useful for monitoring disease activity and treatment response. We assessed the utility of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tumour necrosis factor-like weak inducer of apoptosis (uTWEAK) for disease activity and treatment response monitoring in South Africans with LN. We recruited consenting patients with active LN confirmed on kidney biopsy. Urinary levels of MCP-1 and TWEAK were assayed at baseline and after completion of induction therapy using ELISA methods. We also collected relevant demographic, clinical and biochemical data for patients included in this study. The mean age of patients in this study was 29.8 ± 10.7years, 60% were patients of mixed ancestry, 70% had proliferative LN and mean spot urine proteinuria at baseline was 0.37 (0.18-0.59) g/mmolCr. At completion of induction therapy, the level of uMCP-1 had reduced to 314.5 (IQR: 197.0-622) pg/mgCr from a baseline of 1092.7 (IQR 578.6-1848) pg/mgCr (P = 0.06) while uTWEAK had reduced to 36.0 (IQR 17.0-88.0) pg/mgCr from 159.0 (IQR: 88.5-295.5) pg/mgCr (P = 0.03). For patients reaching early complete or partial remission (n = 17), both biomarkers had significantly declined in their urine: uMCP-1 (P = 0.018) and uTWEAK (P = 0.015). There was no reduction of both biomarkers in patients not achieving remission and no association between uMCP-1 or uTWEAK with renal histological features. Our study shows that uMCP-1 and uTWEAK are elevated in patients with active LN, correlated with the remission status (response to treatment) at the end of induction therapy and can, therefore, be useful for monitoring disease activity and treatment response.

Urinary Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (uTWEAK) and Urinary Monocyte Chemo-attractant Protein-1 (uMCP-1): Promising Biomarkers of Lupus Nephritis Activity?

There is no single biomarker to detect lupus nephritis (LN) activity. Renal biopsy is still the gold standard method but it is invasive and mainly used in the initial assessment of the patients. Urinary tumor necrosis factor-like weak inducer of apoptosis (uTWEAK) and urinary monocyte chemo-attractant protein-1 (uMCP-1) can be secreted in the urine of active LN. The aim of the study is to assess the potential role of uTWEAK and uMCP-1 in lupus patients and to determine their correlation with disease activity. This is a case-control study conducted on a total of 114 subjects; 92 systemic lupus erythematosus (SLE) patients and 22 healthy volunteers. The patients were recruited from the rheumatology unit at the internal medicine department, Tanta University Hospital, Tanta, Egypt. The patients and controls were subjected to full history taking, complete clinical examination, routine laboratory tests, uTWEAK and uMCP-1 measurement, assessment of the disease activity using SLE Disease Activity Index (SLEDAI), and renal SLEDAI (rSLEDAI) scores. uTWEAK and uMCP-1 levels were higher in SLE with active nephritis group than those of other SLE groups and controls. There was a significant positive correlation between uTWEAK and uMCP-1 levels in lupus patients with proteinuria, anti-dsDNA, SLEDAI and r-SLEDAI and a negative correlation with C3 and C4. TWEAK showed a sensitivity of 80.43% and 100% and specificity of 50% and 100% in detecting lupus activity and LN activity, respectively. Furthermore, uMCP-1 showed a sensitivity of 82.6% and 100% and specificity of 50% and 100% in detecting lupus activity and LN activity, respectively. uTWEAK and uMCP-1 are new, easily obtained, accurate markers with high sensitivity and specificity in the detection of LN activity.

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

Serum and urine TNF-like weak inducer of apoptosis, monocyte chemoattractant protein-1 and neutrophil gelatinase-associated lipocalin as biomarkers of disease activity in patients with systemic lupus erythematosus.

TNF-like weak inducer of apoptosis (TWEAK), monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) are proinflammatory cytokines/chemokines that are considered as potential biomarkers reflecting disease activity in systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and extra-renal SLE. Thirty active patients with SLE (15 renal and 15 extra-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 extra-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared to the inactive SLE group (sTWEAK p = 0.005; uTWEAK p = 0.026; sNGAL p < 0.001; uNGAL p = 0.002), whilst no significant differences regarding serum and urine MCP-1 levels were observed (p = 0.189 and p = 0.106, respectively). uTWEAK (p = 0.237), sMCP-1 (p = 0.141), uMCP-1 (p = 0.206), sNGAL (p = 0.419) and uNGAL (p = 0.443) levels did not differ between patients with active renal and extra-renal SLE. Serum TWEAK was higher in patients with active renal SLE (p = 0.006). There were no differences between active renal SLE and active renal AAV. Levels of all biomarkers were correlated with the SLE Disease Activity Index. sTWEAK, uTWEAK, sNGAL and uNGAL are biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV.

Association of NFkB1 Gene Polymorphism with Inflammatory Markers in Patients of Type 2 Diabetes Mellitus with or without Renal Involvement in Eastern India

Aims: To evaluate the association of Nuclear factor kappa B1(NFkB1) gene polymorphism with inflammatory markers Urinary Monocyte Chemoattractant Protein 1 (UMCP1) and Tumor Necrosis Factor alfa (TNF alfa) in Patients of diabetes mellitus with or without renal involvement in Eastern India. Material and Methods: Consecutive Patients of Type 2 Diabetes Mellitus (DM) with or without microalbuminuria attending SCB MEDICAL COLLEGE and HOSPITAL Medical OPDs in between September 2018 to September 2019 were recruited in this study. Patients were subjected to blood and urine investigations. DNA extraction and Restriction fragment Length Polymorphism (RFLP) was done in Department of Biochemistry. Controls were unrelated healthy attendants with no history of Diabetes Mellitus, HTN, Chronic Kidney Disease (CKD). Results: Mean Systolic BP, Fasting Blood Glucose, Post Prandial Blood Glucose, HBA1c, Total Cholesterol were significantly higher in diabetes mellitus and diabetic nephropathy groups than control group. Estimated Glomerular Filtration Rate was significantly lower in diabetic nephropathy (p value < 0.001). UMCP1, Urinary Albumin Creatinine Ratio, TNF alfa were higher in diabetes mellitus and nephropathy with p value (<0.001, 0.006 < 0.001) respectively. In between DM and Diabetic Nephropathy groups nfkb1 gene expression, umcp1 and tnf alfa levels were significantly increased in Diabetic nephropathy with p value 0.019, <0.01, 0.001 respectively. Insertion/insertion NFkB1 gene polymorphisms were more in diabetic nephropathy group and were positively correlated with inflammatory markers UMCP1 (r = 0.517, p < 0.01) and TNF alfa (r = 0.172, p = 0.19). Conclusion: insertion/insertion NFkB1 gene polymorphism increases the risk of nephropathy by 2.52 times (OR = 2.52, 95% CI: 0.04 - 0.63, p value = 0.019) in diabetes patients in eastern India.

Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis.

Prior work has shown that urinary soluble CD163 (usCD163) displays excellent biomarker characteristics for detection of active renal vasculitis using samples that included new diagnoses with highly active renal disease. This study focused on the use of usCD163 in the detection of the more clinically relevant state of mild renal flare and compared results of usCD163 testing directly to testing of urinary monocyte chemoattractant protein-1 (uMCP-1). Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV, n = 88) were identified within a serially sampled, longitudinal and multicentre cohort. Creatinine-normalized usCD163 and uMCP-1 levels were measured by enzyme-linked immunosorbent assay and, both alone and in combination, were compared between times of active renal AAV and during remission and/or active non-renal AAV. Samples from 320 study visits included times of active renal vasculitis (n = 39), remission (n = 233) and active extrarenal vasculitis (n = 48). Median creatinine levels were 0.9 mg/dL [interquartile range (IQR) 0.8-1.2] in remission and 1.4 mg/dL (IQR 1.0-1.8) during renal flare. usCD163 levels were higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 162 ng/mmol (IQR 79-337), 44 (17-104) and 38 (7-76), respectively (P < 0.001). uMCP-1 levels were also higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 10.6 pg/mmol (IQR 4.6-23.5), 4.1 (2.5-8.4) and 4.1 (1.9-6.8), respectively (P < 0.001). The proposed diagnostic cut-points for usCD163 and uMCP-1 were 72.9 ng/mmol and 10.0 pg/mmol, respectively. usCD163 and uMCP-1 levels were marginally correlated (r2 = 0.11, P < 0.001). Combining novel and existing biomarkers using recursive tree partitioning indicated that elevated usCD163 plus either elevated uMCP-1 or new/worse proteinuria improved the positive likelihood ratio (PLR) of active renal vasculitis to 19.2. A combination of usCD163 and uMCP-1 measurements appears to be useful in identifying the diagnosis of subtle renal vasculitis flare.

Urinary epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors for rapid loss of renal function in type 2 diabetic patients with diabetic kidney disease

BackgroundIncreased monocyte chemoattractant protein-1 (MCP-1) and decreased epidermal growth factor (EGF) are promising biomarkers to predict progressive decline in kidney function in non-diabetic kidney diseases. We aimed to evaluate the performance of urinary EGF, MCP-1 or their ratio in predicting rapid decline of GFR in a cohort of Type 2 diabetic patients (T2DM) with diabetic kidney disease (DKD).MethodsT2DM patients (n = 83) with DKD at high risk for renal progression were followed up prospectively. The baseline urine values of MCP-1 to creatinine ratio (UMCP-1), EGF to creatinine ratio (UEGF), EGF to MCP-1 ratio (UEGF/MCP-1) and albumin to creatinine ratio (UACR) were measured. The primary outcome was a decline in estimated glomerular filtration rate (GFR) of ≥25% yearly from baseline.ResultsDuring follow-up time of 23 months, patients with rapid decline in estimated GFR of ≥25% yearly from baseline had significantly higher baseline levels of UMCP-1, and UACR and lower UEGF and UEGF/MCP-1 ratio. All renal biomarkers predicted primary outcomes with ROC (95%CI) for UMCP-1=0.73 (0.62-0.84), UEGF=0.68 (0.57-0.80), UEGF/MCP-1=0.74 (0.63-0.85), and UACR =0.84 (0.75-0.93). By univariate analysis, blood pressure, GFR, UACR, UMCP-1, UEGF, and UEGF/MCP-1 were associated with rapid decline GFR. By multivariate analysis, UACR, systolic blood pressure, and UMCP-1 or UEGF/MCP-1 were independently associated with rapid GFR decline.ConclusionsUMCP-1 or UEGF/MCP-1 ratio were associated with rapid renal progression independent from conventional risk factors in DKD.

Visceral leishmaniasis-associated nephropathy in hospitalised Brazilian patients: new insights based on kidney injury biomarkers.

To evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management of visceral leishmaniasis. Prospective study with 50 hospitalised VL patients. AKI biomarkers, that is, serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL, uNGAL, respectively), urinary kidney injury molecule-1 (uKIM-1) and urinary monocyte chemotactic protein-1 (uMCP-1), were quantified by immunoassay (ELISA). Also, interferon-gamma (INF-y) and C-reactive protein (CRP) were evaluated as inflammatory biomarkers possibly related to VL severity. VL patients had hyponatremia, hypoalbuminemia, hypergammaglobulinemia, haematologic and hepatic disorders. AKI was found in 46%, and one death (2%) occurred. The AKI group had significant longer hospital stay, lower levels of IFN-y and higher levels of CRP, more clinical renal abnormalities and higher levels of sNGAL, uNGAL, uKIM-1 and uMCP-1. Overall, sNGAL, uKIM-1 and uMCP-1 showed correlations with important clinical renal abnormalities, such as proteinuria, albuminuria, serum creatinine and glomerular filtration rate using adjusted correlations with CRP and IFN-y. Only sNGAL showed an early association with AKI development (OR=2.78, 95% CI=1.429-5.428, per each increase of 50ng/ml), even after adjusting for clinical signals of VL severity and for immune biomarkers. Moreover, sNGAL showed a better performance in predicting AKI development (AUC-ROC=0.81, 95% CI=0.69-0.93; cut-off=154ng/ml, sensitivity=82.6%, specificity=74.1%, P<0.001). Visceral leishmaniasis-associated nephropathy showed important proximal tubular injury and glomerular inflammation. Serum NGAL showed an early association with VL-associated nephropathy and may be used to improve clinical management strategies and decrease morbimortality in VL patients.

Combined utilization of untimed single urine of MCP-1 and TWEAK as a potential indicator for proteinuria in lupus nephritis: A case-control study.

The aim of this study was to determine whether combined utilization of untimed single urine monocyte chemoattractant protein 1 (uMCP-1) and tumor necrosis factor (TNF)-like weak inducer of apoptosis (uTWEAK) could serve as a screening test for proteinuria in patients with lupus nephritis (LN).A case-control study that contained 39 biopsy-proven LN patients, 20 non-LN systemic lupus erythematosus (SLE) patients, and 10 healthy controls (HCs) were carried out. Correlations between uMCP-1, uTWEAK, and traditional clinical markers were analyzed by Spearman correlation test. Diagnostic values of uMCP-1, uTWEAK, and urine albumin/creatinine ratio (uACR) in the assessment of proteinuria were investigated by receiver operating characteristic (ROC) curves.Biopsy-proven LN patients showed higher levels of uMCP-1 and uTWEAK than non-LN patients. uMCP-1 and uTWEAK were elevated in renal active patients (rSLEDAI ≥4). Both uMCP-1 and uTWEAK showed significant correlation with patients' rSLEDAI, 24-hour urine proteinuria (24hr UP), and anti-double-stranded DNA (anti-dsDNA) antibodies. No correlations of these 2 biomarkers between cystatin C (Cys-C), creatinine (Cr), and blood urea nitrogen (BUN) were observed. An algorithm combining the moderate sensitivity of uMCP-1 and high specificity of uTWEAK displayed great specificity and sensitivity for proteinuria screening.Both uMCP-1 and uTWEAK were positively correlated with the impairments of LN, and the combined utility of untimed single uMCP-1 and uTWEAK might be used as potential predictors for proteinuria in LN.

Monocyte Chemoattractant Protein-1 in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis: Biomarker Potential and Association with Polymorphisms in the MCP-1 and the CC Chemokine Receptor-2 Gene.

Antineutrophil cytoplasmic autoantibody- (ANCA-) associated vasculitis (AAV) are relapsing-remitting disorders with unpredictable prognosis. There is a need of biomarkers for distinguishing which patients will have a more severe outcome and also for predicting relapses in disease activity. This study confirms the previous results of urinary MCP-1 (uMCP-1) as a prognostic marker and explores its potential as a marker of disease activity. Method. 114 patients with AAV were followed regularly between 2002 and 2011 at Skåne University Hospital. Urine samples, blood samples, and clinical status were registered. The urine samples were analyzed in an in-house-developed ELISA. PCR-RLFP was used to analyze the MCP-1 and CCR2 genes. Results. Patients with severe prognosis had significantly higher levels of uMCP-1 compared to patients with nonsevere prognosis and healthy controls. Patients with renal damage had higher levels compared to patients who did not have renal damage. There was also a tendency of higher uMCP-1 levels in active disease as compared to remission. AA in the -2518 position in the MCP-1 gene was associated with a more severe outcome compared to the A/G or the G/G genotype. The A/A genotype were also associated with higher levels of uMCP-1. No significant associations were seen for the CCR2-V64I. Conclusion. This study confirmed the connection between high uMCP-1 levels and poor prognosis and also disease activity. It also suggests an association of the A/A genotype at position -2518 in the MCP-1 gene and poor prognosis in AAV. uMCP-1 is clearly a candidate biomarker of potential clinical value. The A/A genotype association needs further evaluation.

Longitudinal assessment of monocyte chemoattractant protein-1 in lupus nephritis as a biomarker of disease activity.

Urinary MCP-1 (uMCP-1) levels reflect lupus nephritis (LN) disease activity. However, long-term prospective studies evaluating it as a biomarker are lacking. SLE patients with active nephritis (AN), active disease without nephritis (ANR), and inactive disease (ID) were enrolled. AN patients were followed up every 3months for 1year. Urine and serum samples were collected at baseline from all and at follow-up visits in AN group. Urine samples from healthy subjects (HC), rheumatoid arthritis (RA), and diabetic nephropathy (DM) patients (20 each) served as controls. Serum (sMCP-1) and uMCP-1 was measured using ELISA. Urinary values were normalized for creatinine excretion. Nonparametric tests were used. A total of 121 SLE patients were enrolled. Baseline uMCP-1 was significantly higher in AN as compared to ANR, ID, HC, and RA (p<0.001), but it was not different from DM and showed good correlation with rSLEDAI and SLEDAI (r=0.52 and 0.47, p<0.001) but not with sMCP-1. On ROC analysis to differentiate between AN and ANR, uMCP-1 performed better than sMCP-1, anti-dsDNA antibodies, C3 and C4. uMCP-1 and not sMCP-1 decreased significantly at all follow-up visits (p<0.001). uMCP-1 remained persistently elevated in a patient who developed CKD and rose before conventional markers in two patients with relapse of LN. uMCP-1 correlates well with LN disease activity and helps differentiate between AN and ANR patients. Its levels fall with treatment and may have a potential to predict poor response and relapse of LN. uMCP-1 is most likely generated locally in the kidney.

Urinary monocyte chemoattractant protein-1 and vitamin D-binding protein as biomarkers for early detection of diabetic nephropathy in type 2 diabetes mellitus.

Diabetic nephropathy is a serious complication of both type 1 and type 2 diabetes and, unless arrested, leads to end-stage renal disease. Therefore, early prediction and detection of DN would greatly benefit the disease management and delay its progression. The aim of this study is to evaluate the levels of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary vitamin D-binding protein (uVDBP) in type 2 diabetic patients with different degrees of diabetic nephropathy (DN) and to assess the value of uMCP-1 and uVDBP in the early detection of DN. Seventy-five type 2 diabetic patients with normoalbuminuria (n = 25), microalbuminuria (n = 25), macroalbuminuria (n = 25), and 25 healthy controls were included in this study. Urinary MCP-1 and VDBP levels were evaluated by enzyme-linked immunosorbent assay. A significant elevation in the uMCP-1 and uVDBP levels was found in macroalbuminuric (p < 0.001) and microalbuminuric (p < 0.01) diabetic patients compared to that in normoalbuminuric diabetic patients and control subjects (p < 0.001). Correlation study revealed that both uMCP-1 and uVDBP were significantly positively correlated to urinary albumin/creatinine ratio (r = 0.968, p < 0.001 and r = 0.973, p < 0.001, respectively), serum urea (r = 0.461, p = 0.001 and r = 0.456, p = 0.002, respectively), and serum creatinine (r = 0.475, p = 0.001 and r = 0.448, p = 0.004, respectively) and significantly inversely correlated to glomerular filtration rate (r = -0.983, p < 0.001 and r = -0.988, p < 0.001, respectively). Receiver operating characteristic (ROC) curve analysis of uMCP-1 and uVDBP levels for early diagnosis and detection of DN revealed that the cut-off value of uMCP-1 was 110 pg/mg with 92% sensitivity and 100% specificity; whereas, the cut-off value of uVDBP was 550 ng/mg with 96% sensitivity and 84% specificity. The findings of the present study suggest that uMCP-1 and uVDBP may be considered as novel potential diagnostic biomarkers for the early detection of diabetic nephropathy.

Analysis of urinary TGF-β1, MCP-1, NGAL, and IL-17 as biomarkers for lupus nephritis

This study was aimed to determine the diagnostic performance of transforming growth factor beta 1 (uTGF-β1), monocyte chemoattractant protein-1 (uMCP-1), neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin 17 (uIL-17) in LN. Seventy participants were studied, categorized into three groups: 38 severe LN (class III–IV LN patients); 12 mild LN (class I–II LN patients); and 20 control (healthy volunteers). Diagnosis of SLE was based on the 1997 ARA criteria. Class NL classified according to ISN/RPS 2004. uTGF-β1, uMCP-1, uNGAL, uIL-17 levels were determined by ELISA, using spot urine. The level of uMCP-1 and uNGAL was significantly greater in severe or mild LN compared with control group (P<0.05). The level of uTGF-β1 and uIL-17 was significantly higher in severe LN than that controls group (P<0.05). The AUC of uTGF-β1, uMCP-1, uNGAL, uIL-17 was 66.50%; 86.90%; 87.50%; 71.70%, with the cut-off value of 27.13pg/ml; 1.54pg/ml; 446.30pg/ml; 36.62pg/ml. Only uNGAL showed a significant correlation with the activity (P=0.016; r=0.389) and chronicity indices (P=0.018; r=0.381). This study showed that uTGF-β1, uMCP-1, uNGAL, uIL-17 levels were increased in LN. The AUC values for each biomarker are indicating a good diagnostic value. Urinary NGAL had the best sensitivity and specificity followed by uMCP-1, uIL-17 and uTGF-β1. For combinations of two biomarkers, the best sensitivity and specificity were displayed by the combination of uTGF-β1 & u-NGAL, followed by uMCP-1 & uNGAL.

Urinary monocyte chemoattractant protein-1 levels and interstitial changes in the renal cortex and their relationship with loss of renal function in renal transplant patients with delayed graft function.

BackgroundInflammatory cell infiltration and residual areas of fibrosis in kidneys after renal transplantation can lead to functional abnormalities with long-term implications.ObjectivesThe aim of this study was to determine urinary monocyte chemoattractant protein-1 (uMCP-1) levels, relative cortical interstitial area (RCIA), and cortical tubulointerstitial macrophage infiltration in renal transplant patients with delayed graft function (DGF) and their possible correlation with graft outcome.DesignPatients were followed after biopsies for one year, and their renal function and structure were evaluated, as well as parameters of inflammatory process.SettingClinical Hospital of the School of Medicine of Ribeirão Preto.PatientsTwenty-two cadaveric kidney transplant recipients with DGF were followed for one year.MeasurementsRenal function, RCIA, macrophages infiltration and uMCP-1 levels were evaluated.MethodsRenal function was evaluated by plasma creatinine levels. RCIA was determined by morphometry. Immunohistochemical staining of macrophages was performed using an anti-CD68 monoclonal antibody. uMCP-1 levels were determined using a human MCP-1/CCL2 immunoassay kit.ResultsThere was a significant increase in uMCP-1 levels in transplant patients compared with controls (p < 0.001). RCIA was 7.1% (6.4 to 9.2; median and 25th to 75th percentiles) in controls and 37.1% (28.1 to 43.7) in patients with kidney transplants (p < 0.001). The patients who presented with a higher RCIA in the first biopsy showed higher levels of plasma creatinine one year after transplantation (r = 0.44; p < 0.05). The number of tubulointerstitial macrophages per 0.10 mm2 grid field was higher in the renal cortex of transplant patients compared with the controls (19.4 (9.0 to 47.1) vs. 2.5 (1.8 to 3.4), p < 0.001). There was also a positive correlation between the RCIA and the number of tubulointerstitial macrophages in the renal cortex of these patients (r = 0.49; p < 0.001).LimitationsThe number of patients studied was relatively small and may not be reflecting outcomes over a larger spectrum of kidney cadaveric transplants.ConclusionsOur results demonstrate increased levels of uMCP-1 in transplant patients with DGF, in addition to increased tubulointerstitial macrophage infiltration and RCIA, which could predict the outcome of renal function in these patients.

Urine Monocyte Chemoattractant Protein-1 and Lupus Nephritis Disease Activity: Preliminary Report of a Prospective Longitudinal Study.

Objective. This longitudinal study aimed to determine the urine monocyte chemoattractant protein-1 (uMCP-1) levels in patients with biopsy-proven lupus nephritis (LN) at various stages of renal disease activity and to compare them to current standard markers. Methods. Patients with LN—active or inactive—had their uMCP-1 levels and standard disease activity markers measured at baseline and 2 and 4 months. Urinary parameters, renal function test, serological markers, and renal SLE disease activity index-2K (renal SLEDAI-2K) were analyzed to determine their associations with uMCP-1. Results. A hundred patients completed the study. At each visit, uMCP-1 levels (pg/mg creatinine) were significantly higher in the active group especially with relapses and were significantly associated with proteinuria and renal SLEDAI-2K. Receiver operating characteristic (ROC) curves showed that uMCP-1 was a potential biomarker for LN. Whereas multiple logistic regression analysis showed that only proteinuria and serum albumin and not uMCP-1 were independent predictors of LN activity. Conclusion. uMCP-1 was increased in active LN. Although uMCP-1 was not an independent predictor for LN activity, it could serve as an adjunctive marker when the clinical diagnosis of LN especially early relapse remains uncertain. Larger and longer studies are indicated.

Urinary Monocyte Chemoattractant Protein and Lupus Nephritis Activity

Objective: Monocyte chemoattractant protein-1 (MCP-1) is reported to be associated with lupus nephritis (LN) activity. We therefore investigated urinary MCP-1 (uMCP-1) in patients with biopsy proven LN.Methods: This was a cross-sectional observational study in which uMCP-1 levels and the standard parameters of LN activity were measured in these patients.Results: One hundred patients were recruited: 47 with active and 53 inactive LN. uMCP-1 levels were increased in those with active LN [9,317.5 pg/mg creatinine (5,48.3-40,170)] compared to those with inactive LN [3,682 pg/ mg creatinine (0-23,866)] (p<0.001). uMCP-1 correlated with proteinuria (r=0.39, p=0.001), serum albumin (r=-0.35, p=0.001) and SLEDAI-2K (renal) (r=0.39, p=0.001). Area under receiver operating characteristic (AUROC) curve for uMCP-1 was 0.82 (p=0.001) compared with 0.50 (p=0.95), 0.37 (p=0.50), 0.43 (p=0.26) for anti-ds-DNA Ab, C3 and C4 respectively. AUROC for proteinuria was 0.94 (p<0.001) and for SLEDAI-2K (renal) was 0.96 (p<0.001). Only proteinuria and SLEDAI-2K (renal) were independent predictors of LN activity.Conclusions: uMCP-1 may provide further adjunctive evidence if the clinical diagnosis of LN activity remains uncertain and facilitate improved grading of renal disease activity in this complex disease thus leading to improved treatment and outcome. Serial measurements of uMCP-1 are indicated.

Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population

Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide. It results from diverse etiologies, diabetes being a frontrunner amongst them. Type 2 diabetes mellitus (DM) is being increasingly recognized as a proinflammatory state with increased oxidative stress which enormously increases the risk of micro and macro vascular diseases. This study was planned to explore the possible association between tumor necrosis factor-alpha (TNF-α), urinary monocyte chemoattractant protein-1 (uMCP-1), high-sensitivity C-reactive protein (hsCRP) and parameters of oxidative stress in patients with Type 2 diabetes mellitus (DM) and diabetic chronic kidney disease (DM–CKD). Fifty patients each were recruited in DM, DM–CKD and healthy control groups. Plasma TNF-α, hsCRP and uMCP-1 levels as inflammatory mediators were measured by ELISA, reduced glutathione (GSH), ferric reducing ability of plasma (FRAP) as parameters of antioxidant activity and malondialdehyde (MDA) as marker of oxidative stress, were measured spectrophotometrically. Plasma TNF-α, hsCRP and uMCP-1 were significantly higher in DM–CKD compared to DM and healthy controls. Lipid peroxidation, measured as MDA was significantly higher in patients with DM–CKD as compared to patients with DM and healthy controls. Further, antioxidant capacity of blood measured as FRAP and GSH was found to be significantly lower in patients with DM and DM–CKD as compared to healthy controls (p<0.001). Plasma TNF-α and uMCP-1 showed a significant positive correlation with HbA1c (r=0.441, 0.643), hsCRP (r=0.400, 0.584) and MDA (r=0.423, 0.759) and significant negative correlation with GSH (R=−0.370, −0.800) and FRAP (r=−0.344, −0.684) Increased inflammatory markers viz. TNF-α, hsCRP and uMCP-1 and markers of oxidative stress i.e. increased MDA and decreased GSH and FRAP in DM–CKD suggest an important role of inflammation and oxidative stress in the pathogenesis of renal damage in diabetic patients.

SAT0225 Urinary monocyte chemoattractant protein-1 (UMCP1) in SLE, a biomarker of renal or more general disease?

BackgroundMonitoring SLE disease activity either globally or within individual organ systems is based on scoring methods and serological tests. Specific biomarkers to enhance and improve disease follow-up have been examined....