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Urinary N-acetyl-beta-d-glucosaminidase (NAG) with neutrophil gelatinase-associated lipocalin (NGAL) improves the diagnostic value for proximal tubule damage in diabetic kidney disease.

ABSTRACT: Screening for diabetic kidney disease (DKD) remains a challenge; however, there has been an ongoing research to investigate the diagnostic value of different biomarkers to identify DKD. The aim of this study was to assess the diagnostic value of both N-acetyl-beta-d-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) in the progression of DKD. This cross-sectional case-control study included 92 type 2 diabetic patients with or without DKD. Urinary NAG and NGAL were measured to evaluate their diagnostic values as biochemical markers related to DKD. Both urinary NAG and NGAL levels were significantly higher among patients with DKD. In multiple linear regression analysis, NAG showed a positive significant association with NGAL in the three different adjusted models, while no significant correlation with fasting blood glucose, glycated hemoglobin, serum creatinine, estimated glomerular filtration rate, and albumin creatinine ratio were observed. The area under the curve for NGAL was 0.659 (p?=?0.01) and 0.564 (p?=?0.297) for NAG in DKD patients. This study demonstrates the association between urinary NAG and NGAL as a tubular damage marker for DKD although longitudinal studies are needed to evaluate its diagnostic value.

SUBMITTER: Siddiqui K

PROVIDER: S-EPMC6364253 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Urinary <i>N</i>-acetyl-beta-d-glucosaminidase (NAG) with neutrophil gelatinase-associated lipocalin (NGAL) improves the diagnostic value for proximal tubule damage in diabetic kidney disease.

Siddiqui Khalid K Al-Malki Basim B George Teena Puthiyaparampil TP Nawaz Shaik Sarfaraz SS Rubeaan Khalid Al KA

3 Biotech 20190204 3

Screening for diabetic kidney disease (DKD) remains a challenge; however, there has been an ongoing research to investigate the diagnostic value of different biomarkers to identify DKD. The aim of this study was to assess the diagnostic value of both <i>N</i>-acetyl-beta-d-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) in the progression of DKD. This cross-sectional case-control study included 92 type 2 diabetic patients with or without DKD. Urinary NAG and NGAL were ...[more]

PMID: 30729090

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Project description:BackgroundObstructive sleep apnea (OSA) is a well-established risk factor for hypertension and cardiovascular morbidity and mortality. More recently, OSA has been implicated as an independent risk factor for chronic kidney disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a well-accepted early biomarker of subclinical kidney tubular injury, preceding an increase in serum creatinine. The goal of this study was to determine if an association exists between OSA and increased urinary NGAL levels.MethodsWe prospectively enrolled adult patients from the sleep clinic of an academic medical center. Each underwent polysomnography and submitted a urine specimen upon enrollment. We measured NGAL and creatinine levels on all urine samples before participants received treatment with continuous positive airway pressure (CPAP), and, in a subset of OSA patients, after CPAP therapy. We compared the urinary NGAL/creatinine ratio between untreated participants with and without OSA, and within a subset of 11 OSA patients also after CPAP therapy.ResultsA total of 49 subjects were enrolled: 16 controls based on an apnea-hypopnea index (events with at least 4% oxygen desaturation; AHI-4%) <5 events/hour (mean AHI-4% = 0.59 +/- 0.60); 33 OSA patients based on an AHI-4% >5 events/hour (mean AHI-4% = 43.3 +/- 28.1). OSA patients had a higher mean body-mass index than the control group (36.58 +/- 11.02 kg/m2 vs. 26.81 +/- 6.55 kg/m2, respectively; p = 0.0005) and were more likely to be treated for hypertension (54.5% vs. 6.25% of group members, respectively; p = 0.0014). The groups were otherwise similar in demographics, and there was no difference in the number of diabetic subjects or in the mean serum creatinine concentration (control = 0.86 +/- 0.15 mg/dl, OSA = 0.87 +/- 0.19 mg/dl; p = 0.7956). We found no difference between the urinary NGAL-to-creatinine ratios among untreated OSA patients versus control subjects (median NGAL/creatinine = 6.34 ng/mg vs. 6.41 ng/mg, respectively; p = 0.4148). Furthermore, CPAP therapy did not affect the urinary NGAL-to-creatinine ratio (p = 0.7758 for two-tailed, paired t-test).ConclusionsIn this prospective case-control study comparing patients with severe, hypoxic OSA to control subjects, all with normal serum creatinine, we found no difference between urinary levels of NGAL. Furthermore, CPAP therapy did not change these levels pre- and post-treatment.

Project description:Neutrophil gelatinase associated lipocalin (NGAL), also known as oncogene 24p3, uterocalin, siderocalin or lipocalin 2, is a 24kDa secreted glycoprotein originally purified from a culture of mouse kidney cells infected with simian virus 40 (SV-40). Subsequent investigations have revealed that it is a member of the lipocalin family of proteins that transport small, hydrophobic ligands. Since then, NGAL expression has been reported in several normal tissues where it serves to provide protection against bacterial infection and modulate oxidative stress. Its expression is also dysregulated in several benign and malignant diseases. Its small size, secreted nature and relative stability have led to it being investigated as a diagnostic and prognostic biomarker in numerous diseases including inflammation and cancer. Functional studies, conducted primarily on lipocalin 2 (Lcn2), the mouse homologue of human NGAL have revealed that Lcn2 has a strong affinity for iron complexed to both bacterial siderophores (iron-binding proteins) and certain human proteins like norepinephrine. By sequestering iron-laden siderophores, Lcn2 deprives bacteria of a vital nutrient and thus inhibits their growth (bacteriostatic effect). In malignant cells, its proposed functions range from inhibiting apoptosis (in thyroid cancer cells), invasion and angiogenesis (in pancreatic cancer) to increasing proliferation and metastasis (in breast and colon cancer). Ectopic expression of Lcn2 also promotes BCR-ABL induced chronic myelogenous leukemia in murine models. By transporting iron into and out of the cell, NGAL also regulates iron responsive genes. Further, it stabilizes the proteolytic enzyme matrix metalloprotease-9 (MMP-9) by forming a complex with it, and thereby prevents its autodegradation. The factors regulating NGAL expression are numerous and range from pro-inflammatory cytokines like interleukins, tumor necrosis factor-? and interferons to vitamins like retinoic acid. The purpose of this review article is to examine the expression, structure, regulation and biological role of NGAL and critically assess its potential as a novel diagnostic and prognostic marker in both benign and malignant human diseases.

Dataset Information

Urinary N-acetyl-beta-d-glucosaminidase (NAG) with neutrophil gelatinase-associated lipocalin (NGAL) improves the diagnostic value for proximal tubule damage in diabetic kidney disease.

Publications

Urinary <i>N</i>-acetyl-beta-d-glucosaminidase (NAG) with neutrophil gelatinase-associated lipocalin (NGAL) improves the diagnostic value for proximal tubule damage in diabetic kidney disease.

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