Urinary Neutrophil Gelatinase Associated Lipocalin as a Marker of Tubular Damage in Type 2 Diabetic Patients with and without Albuminuria

ALrefai, Abeer Ahmed; Tayel, Safaa I.; Ragheb, Ahmed; Dala, Ashraf G; Zahran, Ahmed

doi:10.4236/ojneph.2014.41006

Cited by 20 publications

(17 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies reported that renal tubular injury markers including NGAL and KIM-1 were elevated in T2D patients even prior to the incidence of microalbuminuria [39] and in OLETF rats, a rat model of spontaneous T2D, with the presence of marked histopathological tubular damage before obvious albuminuria [40]. These findings are in keeping with those reported herein.…”

Section: Discussionsupporting

confidence: 82%

Amelioration of Early Markers of Diabetic Nephropathy by Linagliptin in Fructose-Streptozotocin-Induced Type 2 Diabetic Rats

Oraby

El-Yamany

Safar

et al. 2019

Nephron

View full text Add to dashboard Cite

Background: Early prediction and clinical intervention are extremely important in order to delay or hinder diabetic nephropathy (DN) progression. Objectives: This study aimed to detect early signs of DN and study the potential ameliorating effect of the dipeptidyl peptidase-4 inhibitor, linagliptin, on some early markers for DN in fructose-streptozotocin (Fr-STZ)-induced diabetic rats. Method: Fr-STZ rats were treated with either linagliptin (3 mg/kg p.o. daily), metformin (350 mg/kg p.o. daily), or their combination for 6 weeks. Results: Fr-STZ DN rats exhibited obvious tubular renal damage and glomerular podocyte injury as confirmed by renal kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and vanin-1 mRNA, as well as urinary N-acetyl-β-D-glucosaminidase elevation and nephrin mRNA suppression, associated with the appearance of marked renal interstitial fibrosis and glomerulosclerosis despite the absence of microalbuminuria. Initiation of oxidative, inflammatory, fibrotic, and apoptotic reactions was evident in the settings of renal hyperglycemia. Linagliptin significantly modulated the aforementioned renal tubular injury makers and restored glomerular nephrin expression as well as reversed renal histopathological alterations. Oxidative, inflammatory, fibrotic and apoptotic processes were also alleviated. Conclusions: This study suggests that linagliptin exerts renoprotection against early features of DN in rats probably by inhibition of high glucose-induced renal tubular and glomerular injury thereby hampering KIM-1 and NGAL as well as vanin-1 associated with renal inflammation, fibrosis and oxidative stress.

show abstract

Section: Discussionsupporting

confidence: 82%

Amelioration of Early Markers of Diabetic Nephropathy by Linagliptin in Fructose-Streptozotocin-Induced Type 2 Diabetic Rats

Oraby

El-Yamany

Safar

et al. 2019

Nephron

View full text Add to dashboard Cite

show abstract

“…A more recent study has reported that U.NGAL was significantly higher in type 2 diabetes patients than in controls and in micro- and macro-albuminuric than in normoalbuminuric patients and was positively correlated to urinary albumin excretion. [ 26 ]…”

Section: Discussionmentioning

confidence: 99%

Evaluation of neutrophil gelatinase-associated lipocalin and cystatin C as early markers of diabetic nephropathy

et al. 2017

View full text Add to dashboard Cite

Introduction:Diabetes mellitus (DM) is a major cause of concern because of its increasing prevalence rate and related microvascular as well as macrovascular complications, including kidney disease. Microalbuminuria has been accepted as the earliest marker for diabetic nephropathy; however, a large proportion of renal impairment occurs in nonalbuminuric state. We planned to investigate the serum and urinary levels of the tubular damage markers (neutrophil gelatinase-associated lipocalin [NGAL] and cystatin C [Cys C]) in patients of type 2 diabetes to detect early kidney injury.Materials and Methods:This cross-sectional hospital-based study included 180 patients with type 2 DM according to the American Diabetes Association criteria. Serum NGAL (S.NGAL) and urine NGAL (U.NGAL) and Cys C were measured in all study participants and investigated for correlation with microalbuminuria.Results:Our results showed that U.NGAL and S.NGAL levels were significantly high in patients with microalbuminuria as compared to normoalbuminuric controls. Serum Cys C was also higher in microalbuminuric patients than who had normoalbuminuria. A positive correlation of urinary albumin excretion with S.NGAL and U.NGAL was noted. U.NGAL also showed positive correlation with duration of diabetes, glycated hemoglobin, and dyslipidemia. Receiver operating characteristic curve analysis showed that the area under the curve for U.NGAL and S.NGAL were 1 and 0.8, respectively, which indicates that they are sensitive markers for early renal damage.Conclusion:Urinary biomarkers were significantly elevated in normoalbuminuric type 2 diabetic patients compared with nondiabetic controls and could be used as markers of nephropathy at a very early stage even before the development of microalbuminuria, the current gold standard for early diagnosis. Despite the promise of these new biomarkers, further large, multicenter prospective studies are still needed.

show abstract

“…It is established that in most cases tubulointerstitial injury determines rather progression of DN than its onset [4, 21]. However, recent studies have shown that elevation of tubular injury markers could occur very early in the settings of DM2 and metabolic disorders, prior to the development of evident DN [31, 32, 40]. …”

Section: Discussionmentioning

confidence: 99%

“…This affirmation is based on the knowledge that hyperglycemia per se could injure tubulointerstitium [4, 21]. Moreover, several clinical studies have indicated high correlation between KIM-1 and NGAL urinary excretion and degree of diabetes compensation [31, 32, 46]. Second limitation is related to the absence of data on ultrastructural renal changes in LD-STZ group at both time points because of the technical issues described above.…”

Section: Discussionmentioning

confidence: 99%

Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes

Bayrasheva

Бабенко

Добронравов

et al. 2016

Journal of Diabetes Research

View full text Add to dashboard Cite

Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) as well as STZ in high doses with preliminary nicotinamide (NA) administration. However, STZ could induce tubulotoxicity. Aim. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks after uninephrectomy, adult male Wistar rats were fed five-week high-fat diet and then received intraperitoneally either LD-STZ (40 mg/kg) or NA (230 mg/kg) followed by STZ (65 mg/kg). Control uninephrectomized vehicle-injected rats received normal chow. At weeks 10, 20, and 30 (the end of the study), metabolic parameters, creatinine clearance, albuminuria, and urinary tubular injury markers (NGAL, KIM-1) were evaluated as well as renal ultrastructural and light microscopic changes at weeks 20 and 30. NA-STZ-group showed higher reproducibility and stability of metabolic parameters. By week 10, in NA-STZ-group NGAL level was significantly lower compared to LD-STZ-group. By week 30, diabetic groups showed early features of DN. However, morphofunctional changes in NA-STZ-group appeared to be more pronounced than those in STZ-group despite lower levels of KIM-1 and NGAL. We proposed a new rat model of DM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes.

show abstract

Urinary Neutrophil Gelatinase Associated Lipocalin as a Marker of Tubular Damage in Type 2 Diabetic Patients with and without Albuminuria

Cited by 20 publications

References 40 publications

Amelioration of Early Markers of Diabetic Nephropathy by Linagliptin in Fructose-Streptozotocin-Induced Type 2 Diabetic Rats

Amelioration of Early Markers of Diabetic Nephropathy by Linagliptin in Fructose-Streptozotocin-Induced Type 2 Diabetic Rats

Evaluation of neutrophil gelatinase-associated lipocalin and cystatin C as early markers of diabetic nephropathy

Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes

Contact Info

Product

Resources

About