Urinary Monocyte Chemotactic Protein-1 Research Articles

Thai traditional massage modulates urinary MCP-1 and relevant inflammatory biomarkers in lower urinary tract symptom patients.

Lower urinary tract symptoms (LUTS) resulting from benign prostatic hyperplasia are a common complaint among elderly men worldwide. Our previous study reported alleviative efficacy of Thai traditional massage (TTM) on LUTS patients. However, underlying mechanism at cellular level remained elusive. Herein, we investigated the effect of TTM on urinary monocyte chemotactic protein-1 (MCP-1) and associative inflammatory biomarkers. Forty-three patients were randomized into two groups: Tamsulosin (n=23) and TTM (n=20). The urinary MCP-1 and interferon-gamma (IFN-γ) levels as well as gene expression levels of MCP-1, Chemotactic protein receptor 2b (CCR2b), IFN-γ, interleukin-1 beta (IL-1β), and transforming growth factor-beta 1 (TGF-β1) were evaluated before and after a four-week treatment. The urinary MCP-1 and IFN-γ levels as well as gene expression levels of MCP-1, CCR2b, IFN-γ, IL-1β, and TGF-β1 were evaluated before and after treatment with Tamsulosin or TTM group. Urinary MCP-1 and IFN-γ levels and the expression levels of five genes from sedimented urine samples were measured using Enzyme-Linked Immunosorbent Assay and quantitative Reverse Transcription Polymerase Chain Reaction, respectively. We observed significant (p<0.05) reduction in the ratio of urinary MCP-1 and creatinine (Cr); MCP-1/Cr levels in subjects given only TTM. There were no significant differences (p<0.05) in IFN-γ/Cr levels in both groups. TTM group down-regulated the expression of IFN-γ whereas up-regulated IL-1β and TGF-β1 mRNA. Our findings suggested TTM had alleviative effects in LUTS patients, which were partially mediated by a reduction of urinary inflammatory cytokines and inflammatory gene expression.

Urinary epidermal growth factor and monocyte chemotactic protein-1 as biomarkers of renal injury in patients with obstructed nephropathy.

To evaluate the role of urinary Monocyte Chemotactic Protein-1 (MCP1) and urinary epidermal growth factor (EGF) in diagnosing of upper urinary tract obstruction (UUTO). Over a period of 6 months (January 2022 to June 2022) this prospective case control comparative study was conducted on 120 participants, 60 of them with UUTO and 60 healthy controls. A morning urine sample of all participants was tested for EGF and MCP-1. after taking a detailed history taking and laboratory and radiological evaluation. Urinary MCP-1(uMCP-1) was significantly (p-value = 0.000) increased in UUTO group showing a mean ± SD of 518.10 ± 51.19 ng/L compared to a mean ± SD of 143.32 ± 58.03 ng/L in the controls, whereas a significantly (p-value = 0.000) decrease of urinary EGF (uEGF) was observed in patients with UUTO compared to control group. A significant difference of uEGF level and uEGF/uMCP1 ratio was observed between mild compared to moderate/severe UUTO. Utilization of the urinary biomarker MCP1, EGF and uEGF/uMCP1 ratio in patients with UUTO can adequately be used as a simple, efficacious and noninvasive way in diagnosis of UUTO.

Steroid Responsiveness and Urinary Monocyte Chemotactic Protein-1 in Children with Nephrotic Syndrome.

Steroid Responsiveness and Urinary Monocyte Chemotactic Protein-1 in Children with Nephrotic Syndrome.

Urinary biomarkers can identify the need for pyeloplasty in presence of supranormal differential renal function in antenatally diagnosed unilateral hydronephrosis

Decision for surgery can be challenging in children with AH (Antenatal Hydronephrosis) especially in the setting of supranormal differential renal function (SnDRF). Aim of this study is to investigate whether IP-10 (interferon gamma-induced protein 10), MCP-1 (monocyte chemotactic protein-1), NGAL (neutrophil gelatinase-associated lipocalin), CA 19-9 (carbohydrate antigen 19-9), and KIM-1 (kidney injury molecule-1) can identify the need for pyeloplasty in presence of SnDRF in antenatally diagnosed unilateral hydronephrosis. A prospectively collected urinary biomarker database was used for the study. There was a total of 53 patients in the AH group. Nineteen children with no history of AH and a normal urinary ultrasonography were taken as controls. Patients with initial ipsilateral DRF (Differential Renal Function) over 50% were included in the SnDRF group while the remaining were named as non-SnDRF. Patients that didn't undergo surgery were classified as non-obstructive dilation (NOD) in both groups. Pyeloplasty was performed in 6/20 patients in SnDRF group, and in 19/33 patients in non-SnDRF group. Biomarker levels in the pyeloplasty and NOD groups were not affected by the presence or absence of SnDRF (p=1.00, for both). Urinary NGAL, and CA 19-9 could determine the need for surgery in SnDRF group with 83% and 100% sensitivity, 86% and 79% specificity, respectively whereas urinary IP-10 and KIM-1 could with 84% and 83% sensitivity, 57% and 71% specificity, respectively. Urinary MCP-1 could differentiate patients who underwent surgery with 83% sensitivity and 50% specificity in SnDRF groups. Our results showed that biomarker levels were not affected whether the kidney has SnDRF. Furthermore, in patients with SnDRF, NGAL and CA 19-9 appear to better estimate requirement for surgical correction before deterioration of renal function.

Risk factors of acute kidney injury induced by multiple wasp stings

In Asia, acute kidney injury (AKI) induced by wasp stings is common; however, the pathophysiological mechanisms involved remain unclear. To evaluate the mechanisms associated with AKI induced by wasp stings, we conducted a retrospective cohort study that assessed blood and urinary samples from 112 patients with hospital admissions resulting from wasp stings. These samples were divided into those with AKI and without AKI as described in the Kidney Disease Improving Global Outcomes (KDIGO) database. Of the patients, 48.2% presented with an elevated number of leukocytes (median 19.9 vs. 15.8 × 109/L), serum creatinine (median 122.0 vs. 66.0 μmol/L), alanine aminotransferase (ALT) (median 176 vs. 32 U/L), aspartate aminotransferase (AST) (median 402 vs. 37 U/L), lactate dehydrogenase (LDH) (median 3076.0 vs. 300.0 U/L), creatine kinase (CK) (median 9990.0 vs. 261.0 U/L), creatine kinase myocardial band (CK-mb) (median 200.0 vs. 29.5 U/L), activated partial thromboplastin time (APTT) (median 70.0 vs. 42.5s), prothrombin time (PT) (median 15.0 vs. 12.5s), myoglobin (median 2200.0 vs. 78.0 ng/mL), proteinuria (51.9% vs. 17.2% ≥ 1+), and urinary monocyte chemotactic protein-1 (MCP-1) (median 432.0 vs. 177.0 pg/mL), and subsequently developed AKI. As determined by multivariate logistic regression analysis, elevated leukocytes (>10 × 109/L) [OR 1.12 (95% CI 1.02–1.23)], high myoglobin (>1200 ng/mL) [OR 18.51 (95% CI 1.51–132.27)], and high urinary MCP-1 (>200 pg/mL) [OR 5.42 (95% CI 1.27–30.39)] on admission were independent risk factors for AKI. At admission, baseline values for ALT, aspartate aminotransferase (AST), LDH, CK-mb, APTT, PT, and proteinuria were higher for those who later died as well as for those who developed end-stage renal disease (ESRD). No patients without AKI died or developed ESRD. The present study explored the pathophysiology of AKI induced by wasp stings based on the findings of risk factors as well as factors related to outcomes. An understanding of AKI induced by wasp stings allows better treatment options and clinical management for wasp stings patients.

Changes of urinary monocyte chemotactic protein 1 and epidermal growth factor and their correlations with clinicopathology in idiopathic membranous nephropathy patients

Objective: To explore the changes and clinical value of urinary monocyte chemotactic protein 1 (MCP-1), epidermal growth factor (EGF) and their ratio in patients with idiopathic membranous nephropathy (IMN). Methods: A total of 67 IMN patients were enrolled according to kidney biopsy in the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2018. The patients included 28 males and 39 females, with an average age of (47.6±14.2) years. Eighteen age-and sex-matched healthy controls were also enrolled. Clinical and pathological data, blood and urine samples of all subjects were collected. Urinary MCP-1 and EGF level were detected by enzyme-linked immunosorbent assay (ELISA). And then the levels of urinary MCP-1, EGF and the ratio of EGF/MCP-1 and their correlations with clinicopathology were analyzed. Results: There was no statistical difference of the urine EGF levels between the two groups [8.3(6.0,12.6) vs 8.4(6.5,10.2) ng/mg Cr, P=0.575]. The urine MCP-1 levels of IMN patients were 0.37 (0.21, 0.69) ng/mg Cr, which was statistical significantly higher than those of the control group [0.09 (0.02, 0.19) ng/mg Cr] (P<0.001), while the EGF/MCP-1 ratio was lower than that of the control group [22.2(15.1,36.6) vs 87.6(71.2,132.7), P<0.001]. Urine MCP-1 was negatively correlated with eGFR (r=-0.303, P=0.012), but positively correlated with the urinary ratio of albumin to creatinin (r=0.368, P=0.002). EGF was positively correlated with eGFR (r=0.722, P<0.001), but negatively correlated with the severity of interstitial fibrosis and renal tubular atrophy (IFTA) (r=-0.312, P=0.011). EGF/MCP-1 ratio was positively correlated with eGFR (r=0.693, P<0.001), but negatively correlated with the severity of the urinary ratio of albumin to creatinin and IFTA (r=-0.261, P=0.028 and r=-0.684, P<0.001, respectively). Further multivariate logistic regression analysis showed that EGF/MCP-1 was a protective factor for moderate-to-severe IFTA (OR=0.891, 95%CI: 0.844-0.949, P=0.008). Conclusion: Patients with IMN have elevated urine MCP-1 level and decreased EGF/MCP-1 ratio, which correlate with clinical indicators. In particular, EGF/MCP-1 ratio is independently related to moderate-severe IFTA, and may be a potential clinical biomarker for diagnosis of IMN.

Urinary Monocyte Chemotactic Protein -1 in Childhood Nephrotic Syndrome

Background Childhood nephrotic syndrome is a clinical entity characterized by massive loss of urinary protein (primarily albuminuria) leading to hypoproteinemia (hypoalbuminemia) and edema. The mechanism of development of childhood nephrotic syndrome is not yet clear. Kidney disease involves an interplay between inflammatory and biochemical changes with the development of innate immune response and accumulation and activation of leucocytes, particularly monocytes/macrophages in the kidney. The moncyte chemotactic protein-1 (MCP-1) is one of the CC chemokine family and it plays an important role in the recruitment of monocytes/macrophages into renal tubulointerstitium. Aim of the Work The aim was to measure the urinary levels of MCP-1 in children with nephrotic syndrome and compare these levels in remission and relapse as well as in steroid sensitive and steroid resistant cases. Patients and method The study included 70 patients with nephrotic syndrome following up in Pediatric Nephrology Clinic, Ain Shams University diagnosed for at least one year and 20 age and sex matched healthy children as control group. Patients with renal impairment and secondary nephrotic syndrome were excluded from the study. Patients were divided into Group A: 35 patients in remission and Group B: 35 patients in relapse. Subgrouping according to the clinical type of nephrotic syndrome was done. Patients were subjected to thorough history taking and careful clinical examination. Routine laboratory investigations were done (s. albumin, s. creatinine, s. cholesterol, complete urialysis and urinary protein/creatinine ratio) together with quantitative determination of urinary monocyte chemotactic protein-1 in cases and controls. Results We found a highly significant difference in urinary MCP-1 between group A, group B, and controls, the highest being group B. the levels in patients in remission still exceeded the controls significantly. However, in group B, no significant difference was found between clinical types of the disease in urinary MCP-1. The same was found in group A. no difference was found between males and females in group A as regards urinary MCP-1 levels yet females had significantly higher levels in group B. This difference was not seen in controls. We found no significant difference in MCP-1 levels in patients receiving different treatment modalities. Conclusion Urinary MCP-1 is a highly sensitive and specific biomarker in childhood nephrotic syndrome (98.5% and 100% respectively), being highly elevated in both remission and relapse, but is not a suitable prognostic biomarker being insignificantly different among different clinical types of nephrotic syndrome.

Acute Kidney Injury Induced by Bothrops Venom: Insights into the Pathogenic Mechanisms.

Acute kidney injury (AKI) following snakebite is common in developing countries and Bothrops genus is the main group of snakes in Latin America. To evaluate the pathogenic mechanisms associated with Bothrops venom nephrotoxicity, we assessed urinary and blood samples of patients after hospital admission resulting from Bothrops snakebite in a prospective cohort study in Northeast Brazil. Urinary and blood samples were evaluated during hospital stay in 63 consenting patients, divided into AKI and No-AKI groups according to the KDIGO criteria. The AKI group showed higher levels of urinary MCP-1 (Urinary monocyte chemotactic protein-1) (median 547.5 vs. 274.1 pg/mgCr; p = 0.02) and urinary NGAL (Neutrophil gelatinase-associated lipocalin) (median 21.28 vs. 12.73 ng/mgCr; p = 0.03). Risk factors for AKI included lower serum sodium and hemoglobin levels, proteinuria and aPTT (Activated Partial Thromboplastin Time) on admission and disclosed lower serum sodium (p = 0.01, OR = 0.73, 95% CI: 0.57–0.94) and aPTT (p = 0.031, OR = 26.27, 95% CI: 1.34–512.11) levels as independent factors associated with AKI. Proteinuria showed a positive correlation with uMCP-1 (r = 0.70, p < 0.0001) and uNGAL (r = 0.47, p = 0.001). FENa (Fractional Excretion of sodium) correlated with uMCP-1 (r = 0.47, P = 0.001) and uNGAL (r = 0.56, p < 0.0001). sCr (serum Creatinine) showed a better performance to predict AKI (AUC = 0.85) in comparison with new biomarkers. FEK showed fair accuracy in predicting AKI (AUC = 0.92). Coagulation abnormality was strongly associated with Bothrops venom-related AKI. Urinary NGAL and MCP-1 were good biomarkers in predicting AKI; however, sCr remained the best biomarker. FEK (Fractional Excretion of potassium) emerged as another diagnostic tool to predict early AKI. Positive correlations between uNGAL and uMCP-1 with proteinuria and FENa may signal glomerular and tubular injury. Defects in urinary concentrations highlighted asymptomatic abnormalities, which deserve further study.

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.

Urinary excretion of EGF and MCP-1 in children with vesicoureteral reflux.

ABSTRACTPurpose The aim of this study was to investigate the urinary concentration of epidermal growth factor (EGF) and monocyte chemotactic protein-1 (MCP-1) as reflux nephropathy (RN) biomarkers before and after endoscopic treatment of moderate to severe vesico-ureteral reflux (VUR).Materials and methods A prospective study was carried out on 72 children with moderate to severe VUR. All patients underwent endoscopic treatment using Macroplastique® or Deflux®. Vesico-ureteral reflux resolution was tested by post-operative voiding cystourethrography after 3 months and 2 years. Follow-up urinary samples were collected at that time. Control samples were taken from healthy children with no clinical evidence of renal and bladder disease and no history of UTI.Results In VUR patients, pre-operative urinary EGF levels had a down-regulation when compared to controls. Following successful VUR repair, urinary EGF levels of VUR children progressively increased only at long term follow-up but without returning to normal levels. Urinary MCP-1 levels were highly expressed in pre-operative samples and decreased markedly during early post-operative measurements. Urinary MCP-1 levels did not further decreased in late post-operative follow-up. In fact, these levels remained significantly higher when compared to controls.Conclusions Urinary levels of EGF and MCP-1 may become useful markers for monitoring the response to surgical treatment in VUR patients. Although endoscopic VUR treatment is effective in reducing the inflammatory response, the persistence of significant abnormal levels of inflammatory cytokines (such as urinary MCP-1) at long term follow-up suggests that surgery alone may not completely treat the chronic renal inflammation evidenced in these children.

Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury

Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in rats by adenine or aristolochic acid models but without increasing serum creatinine. After prolonged recovery (three to six weeks), AKI was induced with a subnephrotoxic dose of cisplatin. Urinary levels of kidney injury molecule-1 (KIM-1), cytochrome C, monocyte chemotactic protein-1 (MCP-1), clusterin, and interleukin-18 increased during CKD induction, without an increase in serum creatinine. After AKI in adenine-induced CKD, serum creatinine increased more rapidly, while increased urinary KIM-1, clusterin, and MCP-1 were delayed and reduced. Increased serum creatinine and biomarker excretion were associated with diffuse tubulointerstitial injury in the outer stripe of outer medulla coupled with over 50% cortical damage. Following AKI in aristolochic acid-induced CKD, increased serum creatinine, urinary KIM-1, clusterin, MCP-1, cytochrome C, and interleukin-18 concentrations and excretion were greater at day 21 than day 42 and inversely correlated with cortical injury. Subclinical CKD modified functional and damage biomarker profiles in diametrically opposite ways. Functional biomarker profiles were more sensitive, while damage biomarker diagnostic thresholds and increases were diminished and delayed. Damage biomarker concentrations and excretion were inversely linked to the extent of prior cortical damage. Thus, thresholds for AKI biomarkers may need to be lower or sampling delayed in the known presence of CKD.

Kidney injury molecules (KIM-1, MCP-1) and type IV collagen in the assessment of activity of antineutrophil cytoplasmic antibody-associated glomerulonephritis

To assess the significance of determining the serum and urinary concentrations of monocyte chemotactic protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), and type IV collagen in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to estimate the activity of renal involvement in AAV. 78 patients (32 men and 46 women) (median age 55 (45; 61) years) with AAV were examined. The patients were divided into 3 groups according to the AAV activity estimated using the Birmingham vasculitis activity Score (BVAS): 1) 25 patients with active ANCA-associated glomerulonephritis (GN); 2) 26 patients with active AAV without renal involvement; 3) 27 patients in sustained AAV remission. The serum and urinary concentrations of the markers were measured by enzyme immunoassay. The urinary concentration of all 3 biomarkers was higher in patients with renal involvement (Group 1); the differences in the levels of MCP-1 and type IV collagen were statistically significant as compared to Groups 2 and 3 (p<0.01), while that in KIM-1 level was only in Group 2. There were statistically significant correlations between the urinary concentration of these biomarkers and the traditional GN activity indices (erythrocyturia, daily proteinuria (DPU), total BVAS scores that reflect renal involvement, as well as serum creatinine levels and estimated glomerular filtration rate (p<0.05). ROC curve analysis showed that the urinary MCP-1 excretion of ≥159 pg/ml had the highest (92%) sensitivity and urinary type IV collagen excretion of ≥3.09 µg/l had the highest (86%) specificity in assessing the activity of ANCA-associated GN. At the same time, their diagnostic value increased in terms of a combination of DPU and ESR (96% sensitivity, 84.9% specificity). The urinary excretion of MCP-1, KIM-1, and type IV collagen reflects the severity of local renal inflammation in AAV patients and a study of these indicators is a promising diagnostic tool for assessing the activity of ANCA-associated GN.

Beneficial Effects of 6-Month Supplementation with Omega-3 Acids on Selected Inflammatory Markers in Patients with Chronic Kidney Disease Stages 1-3.

Introduction Chronic kidney disease (CKD) is accompanied by inflammation. The aim of this study was to evaluate the effect of 6-month supplementation with omega-3 acids on selected markers of inflammation in patients with CKD stages 1–3. Methods Six-month supplementation with omega-3 acids (2 g/day) was administered to 87 CKD patients and to 27 healthy individuals. At baseline and after follow-up, blood was taken for C-reactive protein (CRP) and monocyte chemotactic protein-1 (MCP-1) concentration and white blood cell (WBC) count. Serum concentration of omega-3 acids—eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA)—was determined using gas chromatography. And 24-hour urinary collection was performed to measure MCP-1 excretion. Results After six-month omega-3 supplementation, ALA concentration increased in CKD patients and in the reference group, while EPA and DHA did not change. At follow-up, a significant decrease in urinary MCP-1 excretion in CKD (p = 0.0012) and in the reference group (p = 0.001) was found. CRP, serum MCP-1, and WBC did not change significantly. The estimated glomerular filtration rate (eGFR) did not change significantly in the CKD group. Conclusions The reduction of urinary MCP-1 excretion in the absence of MCP-1 serum concentration may suggest a beneficial effect of omega-3 supplementation on tubular MCP-1 production. Trial Registration This study was registered in ClinicalTrials.gov (identifier: NCT02147002).

Semi-individualised Chinese medicine treatment as an adjuvant management for diabetic nephropathy: a pilot add-on, randomised, controlled, multicentre, open-label pragmatic clinical trial

IntroductionDiabetes mellitus and diabetic nephropathy (DN) are prevalent and costly to manage. DN is the leading cause of end-stage kidney disease. Conventional therapy blocking the renin–angiotensin system has only achieved...

Urinary IP-10, MCP-1, NGAL, Cystatin-C, and KIM-1 Levels in Prenatally Diagnosed Unilateral Hydronephrosis: The Search for an Ideal Biomarker

To investigate the urinary interferon gamma-induced protein 10 (IP-10), monocyte chemotactic protein 1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C, and kidney injury molecule-1 (KIM-1) levels in the management of children with prenatally diagnosed unilateral hydronephrosis. Twenty-seven children with antenatally diagnosed hydronephrosis were enrolled into the study. The controls consisted of 9 healthy children (6 boys, 3 girls; mean age: 41.77 ± 5.30 months). Thirteen children (9 boys, 4 girls; mean age: 48.46 ± 21.11 months) underwent pyeloplasty on follow-up; the remaining 14 (13 boys, 1 girl; mean age: 36.57 ± 14.02 months) were followed up after being diagnosed as having nonobstructive dilatation (NOD). The urinary marker levels were measured in the pyeloplasty, the NOD, and the control groups. The preoperative concentrations of IP-10, MCP-1, NGAL, and KIM-1 were significantly higher in the pyeloplasty group than in the control group (P = .024, P = .002, P = .032, P = .001, respectively). The urinary IP-10 and MCP-1 levels were also significantly higher in the pyeloplasty group than in the NOD group (P = .038, P = .037, respectively). There was no significant difference between the pyeloplasty group and the NOD group regarding urinary NGAL and KIM-1. In the pyeloplasty group, urinary marker levels except cystatin-C were significantly decreased in the postoperative period. A decrease in levels of IP-10, MCP-1, NGAL, and KIM-1 after pyeloplasty may be used as a predictor of surgical outcome. Additionally, IP-10 and MCP-1 were superior to NGAL and KIM-1 in predicting who required surgery.

Urinary monocyte chemotactic protein-1 (MCP-1) in leprosy patients: increased risk for kidney damage.

BackgroundWe aimed to evaluate urinary MCP-1 and oxidative stress through urinary malondialdehyde (MDA) in leprosy and correlate them with traditional, but less sensitive markers of renal disease.MethodsThis is a cross-sectional study of 44 patients with diagnosis of leprosy and no previous treatment. Skin smear was assessed through a bacteriological index - from 0 to 6+. Glomerular filtration rate (GFR), protein excretion rate, microalbuminuria, urinary oxidative stress, malondialdehyde (MDA) and urinary MCP-1 were measured. Also, high- sensitivity C-reactive protein (hs-CRP) was measured in the blood. Fifteen healthy subjects composed a control group.ResultsAge and gender were similar between leprosy patients and control groups. No patient had a GFR < 60 mL/min/1.73 m2 or albumin excretion rate greater than 30 mg/g-Cr. Leprosy patients had higher urinary protein excretion (97.6 ± 69.2 vs. 6.5 ± 4.3 mg/g-Cr, p < 0.001), urinary MCP-1 (101.0 ± 79.8 vs. 34.5 ± 14.9 mg/g-Cr, p = 0.006) and urinary MDA levels (1.77 ± 1.31 vs. 1.27 ± 0.66 mmol/g-Cr, p = 0.0372) than healthy controls. There was a positive correlation between urinary MCP-1 and bacteriological index in skin smears (r = 0.322, p = 0.035), urinary protein excretion (r = 0.547, p < 0.001), albumin excretion rate (r = 0.414, p = 0.006) and urinary MDA (r = 0.453, p = 0.002). After adjusting for hs-CRP, urinary MCP-1 remained correlated with albumin excretion rate (rpartial = 0.483, p = 0.007) and MDA levels (rpartial = 0.555, p = 0.001).ConclusionLeprosy patients with no clinical kidney disease have increased urinary MCP-1 mainly in lepromatous polar form. Inflammatory (MCP-1) and oxidative stress markers suggest leprosy patients are at high risk of developing kidney disease.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-451) contains supplementary material, which is available to authorized users.

Preliminary study on tubuloglomerular dysfunction and evidence of renal inflammation in patients with visceral leishmaniasis.

Visceral leishmaniasis (VL) is a re-emerging zoonosis of worldwide distribution. Monocyte chemotactic protein-1 (MCP-1) and malondialdehyde (MDA) are inflammation biomarkers that have never been investigated in VL. The aim of this study is to investigate the association between renal abnormalities and inflammation biomarkers in VL. This study is a preliminary prospective study with 16 VL adult patients evaluated before treatment compared with a group of 13 healthy volunteers and 5 VL patients evaluated after treatment. Urinary concentration and acidification tests were performed. MCP-1 and MDA were quantified in urine. Urinary concentration deficit was found in all VL patients before (100%) and four VL patients after (80%) treatment. Urinary acidification deficit was found in nine cases before (56.2%) and two cases after (40%) treatment. Urinary MCP-1 (374 ± 359 versus 42 ± 29 pg/mg creatinine, P = 0.002) as well as urinary MDA (5.4 ± 2.6 versus 2.0 ± 0.8 μmol/mL) showed significant differences between VL patients and controls. These data show that VL patients present urinary concentration and acidification deficit, which can persist even after specific treatment. Urinary MCP-1 and MDA are elevated in patients with VL, which suggests renal inflammation and incipient renal damage.

Urinary MCP-1/creatinine in Henoch–Schönlein purpura and its relationship with nephritis

Monocyte chemotactic protein-1 (MCP-1) plays a direct role in the infiltration of macrophages and monocytes during the early stages of Henoch-Schönlein purpura (HSP) nephritis. The aim of this study was to compare the urinary MCP-1/creatinine levels in children with and without HSP nephritis and determine if they are associated with the severity of renal lesions. We included 77 patients with HSP and 25 healthy control children. Levels of serum creatinine, urinalysis, and 12-h proteinuria assessments were performed. Urinary MCP-1 levels were determined by ELISA. Fifty-seven patients had nephritis (74%). Urinary MCP-1/creatinine levels were significantly higher in patients with HSP nephritis (median, 653pg/mg) compared to those with HSP without nephritis (median, 269pg/mg) or healthy children (191pg/mg). In addition, higher MCP-1/creatinine levels were observed in HSP patients who had renal biopsy (median, 1,412pg/mg) in comparison to HSP patients without renal biopsy (median, 302pg/mg). The urinary MCP-1 cut-off value of 530pg/mg could be used to distinguish patients who undergo renal biopsy with a sensitivity of 81% and specificity of 77%. Urinary MCP-1/creatinine levels are elevated in the early stages of severe HSP nephritis and can be used as a biomarker for HSP nephritis.

Endothelial nitric oxide synthase reduces crescentic and necrotic glomerular lesions, reactive oxygen production, and MCP1 production in murine lupus nephritis.

Systemic lupus erythematosus, in both animal models and in humans, is characterized by autoantibody production followed by immune complex deposition in target tissues. Ensuing target organ damage is modulated by reactive intermediates, including reactive nitrogen and oxygen species, through as of now incompletely understood mechanisms. Endothelial nitric oxide synthase is known to impact vascular reactivity; however its impact on reactive intermediate production and inflammatory renal disease is less well defined. In this study, we assessed the impact of endothelial nitric oxide synthase (eNOS) on disease in lupus prone MRL/lpr mice. Mice lacking eNOS developed earlier more severe disease with decreased survival. eNOS deficient mice died sooner and developed significantly more glomerular crescents, necrosis, inflammatory infiltrates and vasculitis, indicating a role for eNOS in modulating these renal lesions. Immune complex deposition was similar between groups, indicating the impact of eNOS is distal to antibody/complement glomerular deposition. Urinary nitric oxide production was decreased in the eNOS deficient mice, while proteinuria was increased. Urinary monocyte chemotactic protein-1 was also increased in the knockout mice. CD4+ T cells from MRL/lpr mice demonstrated mitochondrial hyperpolarization, increased nitric oxide and superoxide production and increased calcium flux compared to B6 control mice. Deficiency of eNOS resulted in decreased nitric oxide and mitochondrial calcium levels but had no effect on mitochondrial hyperpolarization. Renal cortices from MRL/lpr mice that are eNOS deficient demonstrated increased superoxide production, which was blocked by both nitric oxide synthase and NADPH oxidase inhibitors. These studies thus demonstrate a key role for eNOS in modulating renal disease in lupus prone MRL/lpr mice. The impact appears to be mediated by effects on superoxide production in the kidney, impacting downstream mediators such as monocyte chemotactic protein-1. These results suggest that modulation of eNOS may be a novel therapeutic approach to treating lupus nephritis.

Urinary cytokine profiles in unilateral congenital hydronephrosis

BackgroundWe aimed to evaluate possible clinical application of urinary monocyte chemotactic protein-1 (MCP-1), osteopontin (OPN), and regulated upon activation, normal T-cell expressed and secreted (RANTES) chemokine as useful noninvasive markers in children with congenital hydronephrosis (HN) caused by ureteropelvic junction obstruction (UPJO).MethodsThe study cohort consisted of surgical cases (study group 1), comprising 15 children with severe HN who required surgery (median age 1.03 years), conservative cases (study group 2), comprising 21 patients with mild, nonobstructive HN, and control group, comprising 19 healthy children. All children had normal renal function. Urinary (u) concentrations of MCP-1, OPN, and RANTES were measured using immunoenzymatic enzyme-linked immunosorbent assay (ELISA) commercial kits and were expressed in nanograms per milligram creatinine. Increased levels of MCP-1 and OPN were found in children with HN in comparison with study group 2 and controls (p < 0.05). UMCP-1/Cr correlated with half-time (T1/2) of the elimination phase of tracer excretion of technetium-99m-mercaptoacetyltriglycine (99mTc-MAG-3) (p < 0.05).ResultsReceiver operator characteristic (ROC) analyses revealed good diagnostic profile for uMCP-1 only in identifying children (<40 %) with abnormal differential renal function (DRF) [area under the curve (AUC) 0.862], and in detecting kidney injury in all examined children (AUC 0.704).ConclusionsAdditional studies with larger number of patients are required to confirm a potential application of uMCP-1 as a promising parameter for early identification of kidney obstruction.