Neutrophil gelatinase-associated lipocalin as a marker of tubular damage appears to be unrelated to fractional excretion of sodium as a marker of tubular function in septic patients, with or without AKI

Assessment of tubular function is more complicated than the measurement of glomerular filtration rate. Different functions may be affecting according to the different segments of tubule involved. Key tests include concentrating and diluting capacity, and fractional excretion of sodium. Tubular proteinuria occurs when glomerular function is normal, but when the proximal tubules have a diminished capacity to reabsorb and to catabolize proteins, causing an increased urinary excretion of the low-molecular-mass proteins that normally pass through the glomerulus. Proximal tubular dysfunction is characterized by hypophosphataemia, and a variety of other abnormalities characteristics of the renal Fanconi syndrome. Distinguishing the location of the lesion in Renal Tubular Acidosis is considered in Chapter 35.

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Urinary Excretion of Neutrophil Gelatinase-Associated Lipocalin in Diabetic Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2014/961326 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Abraham Said Arellano-Buendía ◽

Fernando Enrique García-Arroyo ◽

Magdalena Cristóbal-García ◽

María Lilia Loredo-Mendoza ◽

Edilia Tapia-Rodríguez ◽

...

Keyword(s):

Oxidative Stress ◽

Urinary Excretion ◽

Serum Levels ◽

Diabetic Rats ◽

Tubular Damage ◽

Tubular Dysfunction ◽

Sod Activity ◽

Expression Levels ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Neutrophil Gelatinase

Recent studies suggest that tubular damage precedes glomerular damage in the progression of diabetic nephropathy. Therefore, we evaluated oxidative stress and urinary excretion of tubular proteins as markers of tubular dysfunction.Methods.Diabetes was induced in rats by streptozotocin administration (50 mg/kg). Oxidative stress was assessed by measuring the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD); additionally, expression levels of 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), and oxidized protein (OP) were quantified. Whole glomerular filtration rate (GFR) was measured. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin (uOPN), and N-acetyl-β-D-glucosaminidase (uNAG) was also determined.Results.Diabetic rats showed an increase in uNGAL excretion 7 days following induction of diabetes. Diuresis, proteinuria, albuminuria, creatinine clearance, and GFR were significantly increased by 30 days after induction. Furthermore, there was an increase in both CAT and SOD activity, in addition to 3-NT, 4-HNE, and OP expression levels. However, GPx activity was lower. Serum levels of NGAL and OPN, as well as excretion levels of uNGAL, uOPN, and uNAG, were increased in diabetics. Tubular damage was observed by 7 days after diabetes induction and was further aggravated by 30 days after induction.Conclusion.The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes.

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Effect of a Single Intravenous Immunoglobulin Infusion on Neutrophil Gelatinase-Associated Lipocalin Levels in Proteinuric Patients With Normal Renal Function

Journal of Investigative Medicine ◽

10.2310/jim.0b013e31818e7e95 ◽

2008 ◽

Vol 56 (8) ◽

pp. 997-1003 ◽

Cited By ~ 20

Author(s):

Davide Bolignano ◽

Giuseppe Coppolino ◽

Carmela Aloisi ◽

Adolfo Romeo ◽

Giacomo Nicocia ◽

...

Keyword(s):

Renal Function ◽

Intravenous Immunoglobulin ◽

Kidney Diseases ◽

Stress Protein ◽

Fractional Excretion ◽

Close Correlation ◽

Renal Diseases ◽

High Dose ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Neutrophil Gelatinase

ABSTRACTThe aim of the present study was to evaluate levels of neutrophil gelatinase-associated lipocalin (NGAL), a stress protein increased after renal and systemic stimuli, in a cohort of 15 patients with severe proteinuria secondary to idiopathic membranous nephropathy and conserved renal function. Neutrophil gelatinase-associated lipocalin levels and the fractional excretion of this protein were higher in patients than in healthy controls. Furthermore, a close correlation was found between serum NGAL and urinary (uNGAL) (r = 0.81; P < 0.01) and between uNGAL and daily proteinuria (r = 0.44; P < 0.03). One hour after infusion of a single high-dose bolus of intravenous immunoglobulin (0.4 g/kg), a new and promising therapy for several kidney diseases, a marked reduction was found in NGAL levels (serum NGAL 194.1 ± 121 vs 370.1 ± 180.5 ng/mL, P < 0.05; urinary NGAL 153.3 ± 108.6 vs 502.2 ± 293.4 ng/mL, P < 0.03); this was maintained 24 hours after the treatment. The findings made suggest that the NGAL balance is altered in patients with severe proteinuria who have not yet developed overt chronic renal failure, thus confirming the potential use of this protein as an early biomarker of kidney damage preceding the increase in serum creatinine levels. Furthermore, also extra-renal cells (neutrophils, endothelium) may hyper-release NGAL, expressing systemic stress related to severe proteinuria. This would explain the impressive decrease occurring in NGAL values after intravenous immunoglobulin infusion, thus providing further evidence of the antiinflammatory properties of this particular therapeutic approach and indicating the possible value of NGAL measurement in monitoring the efficacy of treatment of renal diseases.

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Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients

Blood Purification ◽

10.1159/000506175 ◽

2020 ◽

Vol 49 (5) ◽

pp. 560-566 ◽

Cited By ~ 1

Author(s):

Keren-Lee Rozenfeld ◽

David Zahler ◽

Moshe Shtark ◽

Ilana Goldiner ◽

Gad Keren ◽

...

Keyword(s):

Myocardial Infarction ◽

Renal Damage ◽

Left Ventricular ◽

Adverse Outcomes ◽

Left Ventricular Ejection ◽

Tubular Damage ◽

Renal Tubular Damage ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Renal Tubular ◽

Neutrophil Gelatinase

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Methods: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(–) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(–) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. Results: Of the study patients, 56 (42%) were NGAL(–)/sCr(–), 58 (44%) NGAL(+)/sCr(–), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(–) patients developed the composite endpoint when compared to NGAL(–)/sCr(–) patients (64 vs. 46%; OR 2.1, [95% CI 1.1–4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. Conclusions: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr.

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Urinary Neutrophil Gelatinase-Associated Lipocalin Is Complementary to Albuminuria in Diagnosis of Early-Stage Diabetic Kidney Disease in Type 2 Diabetes

BioMed Research International ◽

10.1155/2017/4691389 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Agnieszka Gala-Błądzińska ◽

Paulina Dumnicka ◽

Beata Kuśnierz-Cabala ◽

Katarzyna Rybak ◽

Ryszard Drożdż ◽

...

Keyword(s):

Type 2 Diabetes ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Early Stage ◽

Control Group ◽

Tubular Damage ◽

Diabetic Kidney ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Neutrophil Gelatinase

Background. Two clinical phenotypes of diabetic kidney disease (DKD) have been reported, that is, with or without increased albuminuria. The aim of study was to assess the usefulness of urinary neutrophil gelatinase-associated lipocalin (uNGAL) for the early diagnosis of DKD in the type 2 diabetes mellitus (T2DM). Methods. The study group consisted of 123 patients with T2DM (mean age 62 ± 14 years), with urine albumin/creatinine ratio (uACR) < 300 mg/g and eGFR ≥ 60 ml/min/1.73 m2. The control group included 22 nondiabetic patients with comparable age, sex, and comorbidities. uNGAL, albumin, and creatinine were measured in the first morning urine samples. uACR and uNGAL/creatinine ratios (uNCR) were calculated. Results. In the control group, maximum uNCR was 39.64 µg/g. In T2DM group, 24 patients (20%) had higher results, with the maximum value of 378.6 µg/g. Among patients with uNCR > 39.64 µg/g, 13 (54%) did not have markedly increased albuminuria. Women with T2DM had higher uNCR than men (p<0.001), without difference in uACR (p=0.09). uNCR in T2DM patients correlated significantly with HbA1c. Sex, total cholesterol, and uACR were independent predictors of uNCR above 39.64 µg/g. Conclusions. Increased uNGAL and uNCR may indicate early tubular damage, associated with dyslipidemia and worse diabetes control, especially in females with T2DM.

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