Plasma neutrophil gelatinase associated lipocalin (NGAL) is associated with kidney function in uraemic patients before and after kidney transplantation

The Medical Research Laboratories, Faculty of Health Sciences, Aarhus University, Aarhus, Denmark.
BMC Nephrology (Impact Factor: 1.69). 02/2012; 13(1):8. DOI: 10.1186/1471-2369-13-8
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Neutrophil gelatinase associated lipocalin (NGAL) is a biomarker of kidney injury. We examined plasma levels of NGAL in a cohort of 57 kidney allograft recipients (Tx group, 39 ± 13 years), a uraemic group of 40 patients remaining on the waiting list (47 ± 11 years) and a control group of 14 healthy subjects matched for age, sex and body mass index (BMI). The kidney graft recipients were studied at baseline before transplantation and 3 and 12 months after transplantation and the uraemic group at baseline and after 12 months.
NGAL was measured using a validated in-house Time-Resolved Immuno-flourometric assay (TRIFMA). Repeated measurements differed by < 10% and mean values were used for statistical analyses. Spearman rank order correlation analysis and the Kruskal-Wallis non-parametric test were used to evaluate the association of NGAL concentrations with clinical parameters.
Plasma NGAL levels before transplantation in the Tx and uraemic groups were significantly higher than in the healthy controls (1,251 μg/L, 1,478 μg/L vs. 163 μg/L, p < 0.0001). In the Tx group NGAL concentrations were associated with serum creatinine (R = 0.51, p < 0.0001), duration of end-stage renal failure (R = 0.41, p = 0.002) and leukocyte count (R = 0.29, p < 0.026). At 3 and 12 months plasma NGAL concentrations declined to 223 μg/L and 243 μg/L, respectively and were associated with homocysteine (R = 0.39, p = 0.0051 and R = 0.47, p = 0.0007).
Plasma NGAL is a novel marker of kidney function, which correlates to duration of end-stage renal failure (ESRD) and serum creatinine in uraemic patients awaiting kidney transplantation. Plasma NGAL is associated with homocysteine in transplanted patients. The prognostic value of these findings requires further studies.

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Available from: Bo Feldt-Rasmussen, Oct 01, 2015
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    • "Graft injury due to ischemia-reperfusion is an inevitable consequence of KTx procedure and can result in varying degrees of early graft dysfunction, which can be considered a form of posttransplantation acute kidney injury. For this reason, several studies investigated the utility of NGAL for the diagnostic and prognostic of acute graft dysfunction following KTx [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27]. Recently, the prognostic value of uNGAL on graft function at one-year after transplantation was also examined and presented conflicting findings [22] [28]. "
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    ABSTRACT: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been suggested as potential early marker of delayed graft function (DGF) following kidney transplantation (KTx). We conducted a prospective study in 40 consecutive KTx recipients to evaluate serial changes of uNGAL within the first week after KTx and assess its performance in predicting DGF (dialysis requirement during initial posttransplant week) and graft function throughout first year. Urine samples were collected on post-KTx days 0, 1, 2, 4, and 7. Linear mixed and multivariable regression models, receiver-operating characteristic (ROC), and areas under ROC curves were used. At all-time points, mean uNGAL levels were significantly higher in patients developing DGF (n = 18). Shortly after KTx (3-6 h), uNGAL values were higher in DGF recipients (on average +242 ng/mL, considering mean dialysis time of 4.1 years) and rose further in following days, contrasting with prompt function recipients. Day-1 uNGAL levels accurately predicted DGF (AUC-ROC = 0.93), with a performance higher than serum creatinine (AUC-ROC = 0.76), and similar to cystatin C (AUC-ROC = 0.95). Multivariable analyses revealed that uNGAL levels at days 4 and 7 were strongly associated with one-year serum creatinine. Urinary NGAL is an early marker of graft injury and is independently associated with dialysis requirement within one week after KTx and one-year graft function.
    Journal of Transplantation 10/2013; 2013(1):650123. DOI:10.1155/2013/650123
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    ABSTRACT: The aim of this study was to investigate the prognostic role of neutrophil gelatinase-associated lipocalin (NGAL) in a large population of patients with ST-segment elevation myocardial infarction. NGAL is a glycoprotein released by damaged renal tubular cells and is a sensitive maker of both clinical and subclinical acute kidney injury. New data have demonstrated that NGAL is also stored in granules of mature neutrophils, and recent data suggest that NGAL may also be involved in the development of atherosclerosis. NGAL is significantly increased in patients with myocardial infarction compared with patients with stable coronary artery disease and healthy subjects. However, the prognostic value of NGAL has never been studied in patients with myocardial infarction. We included 584 consecutive ST-segment elevation myocardial infarction patients admitted to the heart center of Gentofte University Hospital, Denmark, and treated with primary percutaneous coronary intervention, from September 2006 to December 2008. Blood samples were drawn immediately before primary percutaneous coronary intervention. Plasma NGAL levels were measured using a time-resolved immunofluorometric assay. The endpoints were all-cause mortality (n = 69) and the combined endpoints (n = 116) of major adverse cardiac events (MACE) defined as cardiovascular mortality and admission due to recurrent myocardial infarction or heart failure. The median follow-up time was 23 months (interquartile range, 20 to 24 months). Patients with high NGAL (>75th percentile) had increased risk of all-cause mortality and MACE compared with patients with low NGAL (log-rank test, p < 0.001). After adjustment for confounding risk factors chosen by backward elimination by Cox regression analysis, high NGAL remained an independent predictor of all-cause mortality and MACE (hazard ratio: 2.00; 95% confidence interval: 1.16 to 3.44; p = 0.01 and hazard ratio: 1.51; 95% confidence interval: 1.00 to 2.30; p = 0.05, respectively). High plasma NGAL independently predicts all-cause mortality and MACE in ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention.
    Journal of the American College of Cardiology 07/2012; 60(4):339-45. DOI:10.1016/j.jacc.2012.04.017 · 16.50 Impact Factor
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    Scandinavian journal of clinical and laboratory investigation 10/2012; 72(8). DOI:10.3109/00365513.2012.723135 · 1.90 Impact Factor
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