Insights on urinary NGAL obtained in a primary care setting

Tomonaga, Yuki; Szucs, Thomas D.; Ambühl, Patrice M.; Nock, Stefan; Risch, Martin; Risch, Lorenz

doi:10.1016/j.cca.2012.01.001

Cited by 19 publications

(12 citation statements)

References 45 publications

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“…Along the same lines, women had 82% higher levels of NGAL (95% CI 48%-125%, p < 0.0001)[15, 16]. For NGAL, IL-18 and L-FABP, storage time was not significantly associated with biomarker levels in the primary analysis (Table 3), and results were largely consistent for both inpatient and outpatient samples.…”

Section: Resultsmentioning

confidence: 83%

Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study

et al. 2016

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BackgroundAlthough stored urine samples are often used in biomarker studies focused on acute and chronic kidney disease, how storage time impacts biomarker levels is not well understood.Methods866 subjects enrolled in the NIDDK-sponsored ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study were included. Samples were processed under standard conditions and stored at -70°C until analyzed. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and liver fatty acid binding protein (L-FABP) were measured in urine samples collected during the index hospitalization or an outpatient visit 3 months later. Mixed effects models were used to determine the effect of storage time on biomarker levels and stratified by visit.ResultsMedian storage was 17.8 months (25–75% IQR 10.6–23.7) for samples from the index hospitalization and 14.6 months (IQR 7.3–20.4) for outpatient samples. In the mixed effects models, the only significant association between storage time and biomarker concentration was for KIM-1 in outpatient samples, where each month of storage was associated with a 1.7% decrease (95% CI -3% to -0.3%). There was no relationship between storage time and KIM-1 levels in samples from the index hospitalization.ConclusionThere was no significant impact of storage time over a median of 18 months on urine KIM-1, NGAL, IL-18 or L-FABP in hospitalized samples; a statistically significant effect towards a decrease over time was noted for KIM-1 in outpatient samples. Additional studies are needed to determine whether longer periods of storage at -70°C systematically impact levels of these analytes.

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Section: Resultsmentioning

confidence: 83%

Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study

et al. 2016

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“…Of course, flow rates could be calculated subsequent to this but we feel these would be uninterpretable without a baseline. There has also been suggestion that urine osmolality and conductivity could be used as an alternative normalization measures [31]. Assuming a steady state, it could be useful.…”

Section: Discussionmentioning

confidence: 99%

Does Proteinuria-Inducing Physical Activity Increase Biomarkers of Acute Kidney Injury?

Junglee

Lemmey

et al. 2012

Kidney Blood Press Res

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Aim: We sought to determine if an acute kidney injury biomarker, neutrophil gelatinaseassociated lipocalin (NGAL), would be up-regulated by high-intensity proteinuria-inducing exercise. Methods: A prospective cohort design was utilised. 100 healthy, active adults (mean age 24 ± 4 (SD) years) were screened for post-exercise proteinuria (PeP); 10 PeP positive and 10 PeP negative participants then completed a high-intensity exercise protocol involving an 800 meter sprint. Plasma and urinary NGAL, urinary creatinine, urinary albumin and urine volume were obtained at the following time points: pre-run, immediately post-, 25 minutes, one hour and two hours post-run. Results: Following high-intensity exercise, 64% of participants had urinary NGAL concentrations above the normal range, particularly at 25 minutes post (P = 0.002). However, there was no difference in NGAL response between PeP positive and negative groups and plasma NGAL was decreased, not elevated, following exercise (P = 0.002). In some individuals normalizing urinary NGAL for urinary creatinine attenuated elevations. Urinary NGAL was also negatively correlated with urine volume (r = -0.701, P = 0.005). Conclusion: Proteinuria susceptibility did not influence an acute injury biomarker response to exercise. Nevertheless, urinary NGAL was elevated by exercise, possibly due to increased production by the proximal tubule, increased plasma clearance (given the decrease in plasma NGAL) and/or a concentrating effect of exercise-induced oliguria. Until correct normalisation of urinary biomarkers is determined, NGAL should be interpreted cautiously in exercise and acute kidney injury-induced oliguria. The inter-individual NGAL response to exercise also warrants further investigation.

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“…Hence, non-renal diseases may constitute important confounders, when NGAL levels are interpreted with regard to acute kidney injury. Tomonaga et al (2012) showed in a large and heterogenous primary care population that urinary NGAL levels are also dependent on gender, age and liver function and that they correlate with inflammatory parameters. Increased urinary NGAL levels were found in 6.5% of patients in the absence of AKI based on conventional criteria.…”

Section: Ngal In Acute Kidney Injury: From Biology To Pathophysiologymentioning

confidence: 99%

Neutrophil gelatinase‐associated lipocalin: pathophysiology and clinical applications

et al. 2013

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Neutrophil gelatinase-associated lipocalin (NGAL), a 25 kDa protein produced by injured nephron epithelia, is one of the most promising new markers of renal epithelial injury. In contrast to serum creatinine and urinary output, which are measures of kidney function, NGAL is specifically induced in the damaged nephron and then released into blood and urine, where it can be readily measured. Careful proof-of-concept studies using defined animal models have uncovered the sources and trafficking of NGAL in acute kidney injury (AKI) and have addressed the contributions of renal and non-renal sources. Clinical studies indicate that NGAL, unlike creatinine, is a marker responsive to tissue stress and nephron injury, but less so to adaptive hemodynamic responses. In certain clinical settings, NGAL is an earlier marker compared with serum creatinine. In addition, clinical studies have shown that NGAL is a powerful predictor of poor clinical outcomes, which can be used to risk stratify patients when combined with serum creatinine. NGAL has important limitations, including its responsiveness in systemic inflammation, which is partially uncoupled from its response to kidney injury and which needs to be considered when interpreting NGAL results clinically. This review covers the biology and pathophysiology of NGAL and summarizes the results of the growing body of clinical studies that have addressed the utility of NGAL in the early diagnosis of AKI, in the distinction of intrinsic AKI and in the prognostic assessment of broad patient populations.

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Insights on urinary NGAL obtained in a primary care setting

Cited by 19 publications

References 45 publications

Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study

Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study

Does Proteinuria-Inducing Physical Activity Increase Biomarkers of Acute Kidney Injury?

Neutrophil gelatinase‐associated lipocalin: pathophysiology and clinical applications

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