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      Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) for Early Diagnosis of Acute Kidney Injury in Renal Transplant Recipients

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          Abstract

          Background

          Early predictive biomarkers for acute kidney injury (AKI) such as neutrophil elatinase-associated lipocalin (NGAL) could identify patients who may benefit from early initiation of treatment.

          Objectives

          We aimed to obtain a cut off point for AKI prediction by urine NGAL in kidney transplantation.

          Patients and Methods

          In a prospective cohort study, 64 adult who underwent kidney transplantation from living or deceased donors at Baqiyatallah transplant center between April 2009 and January 2010 were included. Patients divided into two groups based on the presence or absence of graft dysfunction. In this study, early graft dysfunction (post transplantation AKI) was defined as Cr level more than 1.5 mg/dL on the second postoperative day.

          Results

          Post-transplant AKI was observed in 31 recipients. Mean urinary NGAL level was greater in recipients with AKI (P = 0.024). In linear regression model, AKI was only factor affected on urinary NGAL level (B = 299.8, P = 0.009). The best sensitivity and specificity for AKI detection by urinary NGAL observed at 2 hour after operation with cut-off point 204 ng/mL.

          Conclusions

          Our study showed in those who developed early post transplantation graft dysfunction the best AUC-ROC for urine NGAL observed at a cut-off value of 204 ng/mL after 2 hour post transplantation.

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          Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review.

          S Coca, R Yalavarthy, J Concato … (2008)
          The diagnosis of acute kidney injury (AKI) is usually based on changes in serum creatinine, but such measurements are a poor marker of acute deterioration in kidney function. We performed a systematic review of publications that evaluated the accuracy and reliability of serum and urinary biomarkers in human subjects when used for the diagnosis of established AKI or early AKI, or to risk stratify patients with AKI. Two reviewers independently searched the MEDLINE and EMBASE databases (January 2000-March 2007) for studies pertaining to biomarkers for AKI. Studies were assessed for methodologic quality. In total, 31 studies evaluated 21 unique serum and urine biomarkers. Twenty-five of the 31 studies were scored as having 'good' quality. The results of the studies indicated that serum cystatin C, urine interleukin-18 (IL-18), and urine kidney injury molecule-1 (KIM-1) performed best for the differential diagnosis of established AKI. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin, IL-18, glutathione-S-transferase-pi, and gamma-glutathione-S-transferase performed best for early diagnosis of AKI. Urine N-acetyl-beta-D-glucosaminidase, KIM-1, and IL-18 performed the best for mortality risk prediction after AKI. In conclusion, published data from studies of serum and urinary biomarkers suggest that biomarkers may have great potential to advance the fields of nephrology and critical care. These biomarkers need validation in larger studies, and the generalizability of biomarkers to different types of AKI as well as the incremental prognostic value over traditional clinical variables needs to be determined.
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            Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study

            Catherine L Dent, Qing Ma, Sudha Dastrala … (2007)
            Introduction Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). The lack of early biomarkers has impaired our ability to intervene in a timely manner. We previously showed in a small cohort of patients that plasma neutrophil gelatinase-associated lipocalin (NGAL), measured using a research enzyme-linked immunosorbent assay, is an early predictive biomarker of AKI after CPB. In this study we tested whether a point-of-care NGAL device can predict AKI after CPB in a larger cohort. Methods First, in a cross-sectional pilot study including 40 plasma samples (NGAL range 60 to 730 ng/ml) and 12 calibration standards (NGAL range 0 to 1,925 ng/ml), NGAL measurements by enzyme-linked immunosorbent assay and by Triage® NGAL Device (Biosite Inc., San Diego, CA, USA) were highly correlated (r = 0.94). Second, in a subsequent prospective uncontrolled cohort study, 120 children undergoing CPB were enrolled. Plasma was collected at baseline and at frequent intervals for 24 hours after CPB, and analyzed for NGAL using the Triage® NGAL device. The primary outcome was AKI, which was defined as a 50% or greater increase in serum creatinine. Results AKI developed in 45 patients (37%), but the diagnosis using serum creatinine was delayed by 2 to 3 days after CPB. In contrast, mean plasma NGAL levels increased threefold within 2 hours of CPB and remained significantly elevated for the duration of the study. By multivariate analysis, plasma NGAL at 2 hours after CPB was the most powerful independent predictor of AKI (β = 0.004, P < 0.0001). For the 2-hour plasma NGAL measurement, the area under the curve was 0.96, sensitivity was 0.84, and specificity was 0.94 for prediction of AKI using a cut-off value of 150 ng/ml. The 2 hour postoperative plasma NGAL levels strongly correlated with change in creatinine (r = 0.46, P < 0.001), duration of AKI (r = 0.57, P < 0.001), and length of hospital stay (r = 0.44, P < 0.001). The 12-hour plasma NGAL strongly correlated with mortality (r = 0.48, P = 0.004) and all measures of morbidity mentioned above. Conclusion Accurate measurements of plasma NGAL are obtained using the point-of-care Triage® NGAL device. Plasma NGAL is an early predictive biomarker of AKI, morbidity, and mortality after pediatric CPB.
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              Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study

              Michael Zappitelli, Kimberly K Washburn, Ayse A Arikan … (2007)
              Introduction Serum creatinine is a late marker of acute kidney injury (AKI). Urine neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of AKI, where the timing of kidney injury is known. It is unknown whether uNGAL predicts AKI in the general critical care setting. We assessed the ability of uNGAL to predict AKI development and severity in critically ill children. Methods This was a prospective cohort study of critically ill children. Children aged between 1 month and 21 years who were mechanically ventilated and had a bladder catheter inserted were eligible. Patients with end-stage renal disease or who had just undergone kidney transplantation were excluded. Patients were enrolled within 24 to 48 hours of initiation of mechanical ventilation. Clinical data and serum creatinine were collected daily for up to 14 days from enrollment, and urine was collected once daily for up to 4 days for uNGAL measurement. AKI was graded using pRIFLE (pediatric modified Risk, Injury, Failure, Loss, End Stage Kidney Disease) criteria. Day 0 was defined as the day on which the AKI initially occurred, and pRIFLEmax was defined as the worst pRIFLE AKI grade recorded during the study period. The χ2 test was used to compare associations between categorical variables. Mann-Whitney and Kruskal-Wallis tests were used to compare continuous variables between groups. Diagnostic characteristics were evaluated by calculating sensitivity and specificity, and constructing receiver operating characteristic curves. Results A total of 140 patients (54% boys, mean ± standard deviation Pediatric Risk of Mortality II score 15.0 ± 8.0, 23% sepsis) were included. Mean and peak uNGAL concentrations increased with worsening pRIFLEmax status (P < 0.05). uNGAL concentrations rose (at least sixfold higher than in controls) in AKI, 2 days before and after a 50% or greater rise in serum creatinine, without change in control uNGAL. The parameter uNGAL was a good diagnostic marker for AKI development (area under the receiver operating characteristic curve [AUC] 0.78, 95% confidence interval [CI] 0.62 to 0.95) and persistent AKI for 48 hours or longer (AUC 0.79, 95% CI 0.61 to 0.98), but not for AKI severity, when it was recorded after a rise in serum creatinine had occurred (AUC 0.63, 95% CI 0.44 to 0.82). Conclusion We found uNGAL to be a useful early AKI marker that predicted development of severe AKI in a heterogeneous group of patients with unknown timing of kidney injury.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nephrourol Mon
                Journal ID (iso-abbrev): Nephrourol Mon
                Journal ID (doi): 10.5812/numonthly
                Journal ID (publisher-id): Kowsar
                Title: Nephro-urology Monthly
                Publisher: Kowsar
                ISSN (Print): 2251-7006
                ISSN (Electronic): 2251-7014
                Publication date (Electronic): 30 March 2013
                Publication date (Print): Spring 2013
                Volume: 5
                Issue: 2
                Pages: 745-752
                Affiliations
                [1 ]Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
                Author notes
                [* ]Corresponding author: Zohreh Rostami, Corresponding author: Zohreh Rostami, Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran. Tel: +98-9121544897, Fax: +98-2181262073, E-mail: rostami@ 123456numonthly.com .
                Article
                DOI: 10.5812/numonthly.9385
                PMC ID: 3703133
                PubMed ID: 23841038
                SO-VID: 4005ace3-c210-40e0-98ed-f6bac239730d
                Copyright © Copyright © 2013, Nephrology and Urology Research Center
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 01 December 2012
                Date revision received : 12 December 2012
                Date accepted : 29 December 2012
                Categories
                Subject: Research Article

                Keywords: neutrophil gelatinase-associated lipocalin protein, rat,acute kidney injury,kidney transplantation
                Data availability:
                Keywords: neutrophil gelatinase-associated lipocalin protein, rat, acute kidney injury, kidney transplantation

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