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      Pathological and Prognostic Value of Urinary Neutrophil Gelatinase-Associated Lipocalin in Macroproteinuric Patients with Worsening Renal Function

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          Background/Aims: Persistent proteinuria is a sign of renal damage caused by several factors, but it is itself a cause of tubular injury leading to chronic renal failure. Neutrophil gelatinase-associated lipocalin (NGAL) is a stress protein released by tubular cells which urinary excretion (uNGAL) increases in response to various stimuli. Methods: In the present study we analyzed uNGAL levels in 23 macroproteinuric patients with membranous glomerulonephritis. Results: In these subjects, uNGAL concentrations were significantly higher than in controls, directly correlated with proteinuria and inversely related to residual renal function. Patients were further categorized into two groups, according to a cut-off baseline uNGAL value of 350 ng/ml and evaluated during a 1-year follow-up period. After 12 months, subjects with higher uNGAL levels showed a significant worsening in baseline renal function and a 3.36 risk ratio of developing a severe decrease in GFR (≧50% of baseline values) compared with others. Conclusions: These findings suggest that NGAL may play a key role in tubular adaptations to persistent macroproteinuria. Furthermore, a new, interesting application of NGAL measurement could be proposed in clinical nephrology as a predictor of worsening renal function in patients affected by chronic kidney disease.

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          Most cited references 6

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          Dual action of neutrophil gelatinase-associated lipocalin.

          Neutrophil gelatinase-associated lipocalin (NGAL) is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL exerts bacteriostatic effects, which are explained by its ability to capture and deplete siderophores, small iron-binding molecules that are synthesized by certain bacteria as a means of iron acquisition. Consistently, NGAL deficiency in genetically modified mice leads to an increased growth of bacteria. However, growing evidence suggests effects of the protein beyond fighting microorganisms. NGAL acts as a growth and differentiation factor in multiple cell types, including developing and mature renal epithelia, and some of this activity is enhanced in the presence of siderophore:iron complexes. This has led to the hypothesis that eukaryotes might synthesize siderophore-like molecules that bind NGAL. Accordingly, NGAL-mediated iron shuttling between the extracellular and intracellular spaces may explain some of the biologic activities of the protein. Interest in NGAL has been sparked by the observation that NGAL is massively upregulated after renal tubular injury and may participate in limiting kidney damage. This review summarizes the current knowledge about the dual effects of NGAL as a siderophore:iron-binding protein and as a growth factor and examines the role of these effects in renal injury.
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            Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin.

            Acute renal failure secondary to ischemic injury remains a common problem, with limited and unsatisfactory therapeutic options. Neutrophil gelatinase-associated lipocalin (NGAL) was recently shown to be one of the maximally induced genes early in the postischemic kidney. In this study, the role of NGAL in ischemic renal injury was explored. Intravenous administration of purified recombinant NGAL in mice resulted in a rapid uptake of the protein predominantly by proximal tubule cells. In an established murine model of renal ischemia-reperfusion injury, intravenous NGAL administered before, during, or after ischemia resulted in marked amelioration of the morphologic and functional consequences, as evidenced by a significant decrease in the histopathologic damage to tubules and in serum creatinine measurements. NGAL-treated animals also displayed a reduction in the number of apoptotic tubule cells and an increase in proliferating proximal tubule cells after ischemic injury. The results indicate that NGAL may represent a novel therapeutic intervention in ischemic acute renal failure, based at least in part on its ability to tilt the balance of tubule cell fate toward survival.
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              Neutrophil-Gelatinase-Associated Lipocalin and Renal Function after Percutaneous Coronary Interventions

              Background/Aims: The value of neutrophil-gelatinase-associated lipocalin (NGAL), a novel biomarker in the detection of acute renal failure in children after cardiac surgery, has been highlighted in previous studies. The incidence of percutaneous coronary intervention (PCI) increases, which may possibly result in increased incidences of contrast nephropathy, its potentially serious complication. Therefore, the aim of our study was to assess prospectively NGAL in patients undergoing elective PCI in relation to serum creatinine. Methods: NGAL was assessed in the serum and urine using commercially available kits. Results: We measured urinary and serum NGAL before, and 2, 4, 12, 24 and 48 h after PCI. We found a significant rise in serum NGAL 2 and 4 h after PCI, and a rise in urinary NGAL 4 and 12 h after PCI. Before PCI, serum NGAL was significantly associated with serum creatinine, urea, urinary NGAL, hemoglobin, hematocrit, albumin, age and presence of diabetes. In multivariate analysis, serum creatinine was the only predictor of serum NGAL. Serum NGAL 2 h after PCI correlated with serum creatinine, duration of PCI, HbA1c, hematocrit, hemoglobin and urinary NGAL. In multivariate analysis, the only predictors of serum NGAL 2 h after PCI were serum creatinine, time of PCI and HbA1c. Serum NGAL before PCI was significantly higher in diabetics than in non-diabetics. Conclusions: NGAL may represent a sensitive early biomarker of renal impairment after PCI. Serum creatinine, duration of PCI, but not type and amount of contrast agent, and appropriate treatment of diabetes, reflected by HbA1c, predict a rise in serum NGAL and kidney function following PCI.

                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                September 2008
                28 August 2008
                : 31
                : 4
                : 274-279
                aChair of Nephrology, Department of Internal Medicine, and bDepartment of Pathology and Experimental Microbiology, University of Messina, Messina, Italy
                151665 Kidney Blood Press Res 2008;31:274–279
                © 2008 S. Karger AG, Basel

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                Page count
                Figures: 3, Tables: 2, References: 13, Pages: 6
                Original Paper


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