Urinary excretion of EGF and MCP-1 in children with vesico-ureteral reflux

ABSTRACT Purpose 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.

Role of Urinary Levels of Endothelin-1, Monocyte Chemotactic Peptide-1, and N-Acetyl Glucosaminidase in Predicting the Severity of Obstruction in Hydronephrotic Neonates

PURPOSE: Antenatal hydronephrosis (AH) is found in 0.5%-1% of neonates. The aim of the study was to assess the urinary concentrations of 3 biomarkers, endothelin-1 (ET-1), monocyte chemotactic peptide-1 (MCP-1), and N-acetyl-glucosaminidase (NAG) in severely hydronephrotic neonates. MATERIALS AND METHODS: Neonates with a history of prenatal hydronephrosis were enrolled in the prospective study in 2 groups. Group 1 included neonates with severe forms of obstruction requiring surgical intervention and group 2 included neonates with milder forms of obstruction without any functional impairment. Fresh voided urinary levels of ET-1, MCP-1, and NAG were measured and their ratios to urinary Cr were calculated. RESULTS: Fourty-two neonates were enrolled into the 2 groups: group 1, 24 patients (21 male, 3 female); group 2, 18 neonates (16 male, 2 female). There were no statistically significant differences between urinary ET-1, NAG, MCP-1 values, and ET-1/Cr and NAG/Cr ratios in groups 1 and 2. The urinary MCP-1/Cr ratio was significantly higher in group 1 than in group 2. For comparison of groups 1 and 2, the cut-off values were measured as 0.5709 ng/mg (sensitivity, 75%; specificity, 67%; positive predictive value [PPV], 71%; negative predictive value [NPV], 71%), 0.927 ng/mg (sensitivity, 77%; specificity, 72%; PPV, 77%; NPV, 72%), and 1.1913 IU/mg (sensitivity, 62%; specificity, 67%; PPV, 68%; NPV, 60%) for ET-1/Cr, MCP-1/Cr, and NAG/Cr ratios, respectively. CONCLUSIONS: The urinary MCP-1/Cr ratio is significantly elevated in neonates with severe obstruction requiring surgical intervention. Based upon these results, urinary MCP-1/Cr may be useful in identification of severe obstructive hydronephrosis in neonates.

Urinary Sodium Excretion Has Positive Correlation with Activation of Urinary Renin Angiotensin System and Reactive Oxygen Species in Hypertensive Chronic Kidney Disease

It is not well described the pathophysiology of renal injuries caused by a high salt intake in humans. The authors analyzed the relationship between the 24-hr urine sodium-to-creatinine ratio (24HUna/cr) and renal injury parameters such as urine angiotensinogen (uAGT/cr), monocyte chemoattractant peptide-1 (uMCP1/cr), and malondialdehyde-to-creatinine ratio (uMDA/cr) by using the data derived from 226 hypertensive chronic kidney disease patients. At baseline, the 24HUna/cr group or levels had a positive correlation with uAGT/cr and uMDA/cr adjusted for related factors (P or =200 mEq/g cr was higher than in patients with or =200 mEq/g cr (P=0.016). During the 16-week follow-up period, an increase in urinary sodium excretion predicted an increase in urinary angiotensinogen excretion. In conclusion, high salt intake increases renal renin-angiotensin-system (RAS) activation, primarily, and directly or indirectly affects the production of reactive oxygen species through renal RAS activation.

Urinary monocyte chemoattractant protein-1 [MCP-1] correlates with prameters of renal injury in type II diabetes mellitus

Diabetic nephropathy [DN] is the leading cause of end stage renal disease in western world. Increased number of interstitial macrophages has been observed in biopsies from patients with DN. Monocyte chemoattractant protein-1 [MCP-1] is the strongest known chemotactic factor for monocytes and is upregulated in DN. We examined urinary level of MCP-1 in type 2 DM patients to assess the possible correlation between its level and the parameters of renal injury. Urinary MCP-1 level was assessed in 75 patients with type 2 DM [25 with and 25 without microabluminuria and 25 with macroalbuminuria and renal impairment] and compared with matched healthy control subjects. HBA1c and estimated glomerular filtration rate [eGFR] derived from the abbreviated Modification of Diet in Renal Disease [MDRD] equation were examined in the study groups in relation to the urinary MCP-1. urinary MCP-1 level was significantly higher in patients with micro and macroalbuminuria [167.4 +/- 50.23 and 630.87 +/- 318.10 ng/g creatinine respectively] as compared with normoalbuminuric patients and healthy controls [63.85 +/- 21.15 and 61.50 +/- 24.81 ng/g creatinine, p<0.0001]. MCP-1 correlated positively with urine albumin/creatinine ratio [ACR] [r=0.75, p<0.001], HBA1c [r=0.55, p<0.001] and inversely with eGFR [r=-0.60, p<0.001]. The study findings suggest that hyperglycemia is associated with increased urinary levels of MCP-1 that is closely linked to renal damage as reflected by proteinuria and eGFR levels. Collectively, these findings suggest that MCP-1 is involved in the pathogensis of diabetic nephropathy throughout its variable stages

Serum chemokines in lupus nephritis and SLE disease activity

To estimate the serum macrophage inflammatory protein-1alpha [MIP-1alpha] and serum/urinary monocyte chemoattractant protein-1 [MCP-1] in systemic lupus erythematosus [SLE] patients. This is in order to highlight their possible roles in the pathogenesis of SLE, disease activity and renal involvement. Forty SLE patients [group I] and 20 apparently healthy controls [group II] were included in the study. SLE patients were subdivided into group IA patients with active lupus nephritis [13 patients] and group IB patients without nephritis [27 patients]. Nephritis was diagnosed by active urinary sediments, impaired serum creatinine or creatinine clearance and graded by renal biopsy according to the WHO classification. SLE activity was measured using SLEDAI. The serum MIP-1 and serum/urinary MCP-1 were measured in all patients and controls using the ELISA technique. SLE patients had a significantly higher level of serum MIP-1alpha in group IA [105.2 +/- 12.9 pgm/mL] and group IB [93.9 +/- 3.5 pgm/mL] when compared to the control group [69.1 +/- 4.9 pgm/mL]. Also, there was a significant positive correlation [p<0.05] between MIP-Ialpha and both clinical [SLEAI], serological [dsDNA, ESR levels] parameters of disease activity and serum/urinary MIP1alpha. There was a statistically significant difference between the means of MCP-1 [serum 16.40 +/- 5.97 and urinary 21.20 +/- 3.12] among the controls and SLE group IA [serum 488.6 + 354.61, urinary 590.3 +/- 339.54], also between the controls and SLE group IB [serum 32.20 +/- 12.65, urinary 35.5 +/- 18.55]. The serum and urinary MCP-1 showed positive correlation with disease activity [SLEDAI], serum creatinine, and creatinine clearance. Also, urinary MCP-1 had positive correlation with ESR. Again, there was a significant difference between groups IA and IB regarding serum levels of MIP-1alpha and serum/urinary MCP-1 [p < 0.05]. The levels of serum MIP-1alpha and the serum/urinary MCP-1, may be used as laboratory parameters of disease activity in SLE and may reflect its immunopathogentic role and proinflammatory activity in SLE. Also, the urinary MCP-1 may be a useful simple tool for monitoring disease activity of lupus nephritis