A comparison of three commercial platforms for urinary NGAL in critically ill adults.

BACKGROUND: Early biomarkers for acute kidney injury (AKI) diagnosis are needed since an increase in serum creatinine levels is a late marker. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most promising AKI biomarkers. Prior to routine clinical use, it is necessary to evaluate and validate a high-throughput commercially available method for NGAL detection. The aim of this study was to do an independent validation and comparison of the analytical performance of three different commercially available urine NGAL (uNGAL) assays. METHODS: Urine samples (n=110) were obtained from various patient groups with and without AKI. All urine samples were processed using Architect NGAL assay, Siemens Advia® 2400 NGAL test, and Siemens Dimension Vista® NGAL Test™, based on the three different platforms. RESULTS: Overall, there was good agreement among the three assays: Spearman's rank correlation coefficient between Architect and Vista was 0.989 (95% confidence interval [CI], 0.983-0.993), between Architect and Advia, 0.962 (95% CI, 0.937-0.977), between Vista and Advia 2400, 0.975 (95% CI, 0.961-0.984). We observed a negative bias of Architect compared with the other assays: comparing Architect to Vista, the mean bias was -55.7 ng/mL (95% CI, -74.3 to -37.0 ng/mL); comparing Architect to Advia 2400, the mean bias was -40.9 ng/mL (95% CI, -56.4 to -25.4 ng/nL). The bias is proportional to the concentration of uNGAL and is more pronounced at higher levels, while irrelevant near the tested cutoff levels of 100 and 190 ng/mL. Comparing Vista and Advia 2400, the mean bias was 10.1 ng/mL (95% CI, 1.5-18.8 ng/mL). Intra-assay imprecision was generally acceptable across all assays; coefficient of variation ranged from 0.8% to 5.3%. CONCLUSIONS: All three methods for uNGAL showed acceptable performance for the tested parameters and are comparable with each other at clinically relevant cutoffs. However, Architect yields lower results than the other two methods, with a bias more pronounced at higher uNGAL concentrations, suggesting additional standardization efforts will likely be necessary to better harmonize the uNGAL methods at various clinically relevant cutoffs.

Reference ranges for serum ß-trace protein in neonates and children younger than 1 year of age.

BACKGROUND: ß-Trace protein (BTP) has been proposed as an alternative endogenous marker of glomerular filtration rate. Data on BTP reference ranges in young children are scarce. We therefore aim to establish reference ranges and examine the developmental course of serum BTP in basically healthy children younger than 1 year of age. METHODS: Single blood samples were taken from healthy children (born at gestational age ≥37 weeks) <12 months of age. Serum BTP was measured using the N latex B-trace protein assay (Siemens Diagnostics, Deerfield, IL, USA) on an Immage® 800 Rate Nephelometer (Beckman Coulter Inc. Brea, CA, USA). Serum creatinine and cystatin C were additionally determined and compared to reference values to confirm a normal renal function. RESULTS: From June 2010 to January 2014, 95 blood samples were collected from 95 children {67.4% male; median age 120 days [inter quartile range 57-166]}. BTP was normally distributed (mean concentration 0.84±standard deviation 0.35 mg/L). Considering all children, the 50th centile BTP reference concentration was 0.82 mg/L (5th-95th centiles; 0.27-1.38). BTP concentrations were the highest in neonates and steadily declined with increasing age (Spearman's rank correlation was -0.415, p=0.002). No gender differences were found. CONCLUSIONS: Our data provide a BTP reference range for the first year of life. Seeing the biological pattern of BTP, with only a limited postnatal decline, this marker might offer a promising alternative to serum creatinine-based methods for estimating glomerular filtration rate in newborns.

Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney injury: a review of the laboratory characteristics and clinical evidences.

Acute kidney injury (AKI) is a common and serious condition, currently diagnosed by functional biomarkers, such as serum creatinine measurements. Unfortunately, creatinine increase is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury has hampered our ability to translate promising experimental therapies to human AKI. The recent discovery, translation and validation of neutrophil gelatinase-associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed here. NGAL may be measured by several methods both in plasma and urine for the early diagnosis of AKI and for the prediction of clinical outcomes, such as dialysis requirement and mortality, in several common clinical scenarios, including in the intensive care unit, cardiac surgery and renal damage due the exposition to toxic agent and drugs, and renal transplantation. Furthermore, the predictive properties of NGAL, may play a critical role in expediting the drug development process. A systematic review of literature data indicates that further studies are necessary to establish accurate reference population values according to age, gender and ethnicity, as well as reliable and specific decisional values concerning the more common clinical settings related to AKI. Furthermore, proper randomized clinical trials on renal and systemic outcomes comparing the use of NGAL vs. standard clinical practice are still lacking and accurate cost-benefit and/or cost-utility analyses for NGAL as biomarker of AKI are also needed. However, it is important to note that NGAL, in the absence of diagnostic increases in serum creatinine, is able to detect some patients affected by subclinical AKI who have an increased risk of adverse outcomes. These results also suggest that the concept and definition of AKI might need to be reassessed.

Preliminary reference intervals for cystatin C and beta-trace protein in preterm and term neonates.

OBJECTIVE: To determine the reference intervals for serum cystatin C (CysC) and beta-trace protein (BTP) as markers of renal function in preterm and term neonates. DESIGN AND METHODS: Blood samples of 128 neonates (34% female) admitted to the NICU were analyzed to determine the levels of serum creatinine (enzymatically), CysC and BTP (nephelometric, Siemens Health Care). RESULTS: The reference intervals, categorized by age, were reported for the 128 neonates. Median (lower/upper limit) BTP were 1.85 (0.57/3.16) and 1.27 (0.51/2.07) mg/L on days 1 and 3. In keeping with maturation of renal function after birth, CysC and BTP fell from days one to day three after birth, whereas creatinine did not. CONCLUSION: Our data provides reference intervals for the levels of creatinine, CysC, and BTP in neonates on days 1 and 3 after birth and demonstrates that CysC and BTP reflect neonatal renal function, whereas creatinine reflects maternal renal function.

Changes in the concentrations of creatinine, cystatin C and NGAL in patients with acute paraquat self-poisoning.

An increase in creatinine > 3 µmol/L/h has been suggested to predict death in patients with paraquat self-poisoning and the value of other plasma biomarkers of acute kidney injury has not been assessed. The aim of this study was to validate the predictive value of serial creatinine concentrations and to study the utility of cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) as predictors of outcome in patients with acute paraquat poisoning. The rate of change of creatinine (dCr/dt) and cystatin C (dCyC/dt) concentrations were compared between survivors and deaths. Receiver-operating characteristic (ROC) curves were constructed to determine the best threshold for predicting death. Paraquat was detected in 20 patients and 7 of these died between 18 h and 20 days post-ingestion. The dCr/dt ROC curve had an area of 0.93 and the cut-off was > 4.3 µmol/L/h (sensitivity 100%, specificity 85%, likelihood ratio 7). The dCyC/dt ROC curve had an area of 0.97 and the cutoff was > 0.009 mg/L/h (sensitivity 100%, specificity 91%, likelihood ratio 11). NGAL did not separate survivors from deaths. Death due to acute paraquat poisoning is associated with changes in creatinine and cystatin concentrations. Further validation of these measurements is needed before they can be adopted in guiding intensive treatments.