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Urinary NGAL and RBP Are Biomarkers of Normoalbuminuric Renal Insufficiency in Type 2 Diabetes Mellitus.

ABSTRACT: Objectives:As a screening index of diabetic kidney disease (DKD), urinary albumin/creatine ratio (UACR) is commonly used. However, approximately 23.3%-56.6% of DKD patients with estimated?glomerular?filtration?rate?(eGFR) < 60?ml/min per 1.73?m2 are normoalbuminuric. Thus, urinary biomarkers of nonalbuminuric renal insufficiency in type 2 diabetes mellitus (T2DM) patients are urgently needed. Methods:This cross-sectional study enrolled 209 T2DM patients with normoalbuminuria whose diabetes duration was more than 5 years. The patients were classified into two groups, NO-CKD (eGFR ? 60?ml/min per 1.73?m2, n = 165) and NA-DKD (eGFR < 60?ml/min per 1.73?m2, n = 44). Levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein (RBP), plasminogen activator inhibitor-1 (PAI-1), vascular cell adhesion molecule-1 (VCAM-1), and E-cadherin were detected, and their correlations with eGFR, plasma TNF-?, IL-6, endothelin-1 (ET-1), and 8-hydroxydeoxyguanosine (8-OHdG) were assessed. Results:Among patients with renal insufficiency, 26.0% was normoalbuminuric. Compared to the NO-CKD group, the NA-DKD group was older with lower hemoglobin (HB) levels and higher systolic blood pressure (SBP), plasma TNF-?, IL-6, and 8-OHdG levels. Logistic regression analysis suggested that age, TNF-?, and 8-OHdG were independent risk factors for nonalbuminuric renal insufficiency. Compared to the NO-CKD group, the NA-DKD group exhibited significant increases in urinary NGAL and RBP levels but not PAI-1, VCAM-1, and E-cadherin. Urinary NGAL and RBP both correlated negatively with eGFR and positively with plasma IL-6 and 8-OHdG. Multiple linear regression indicated NGAL (? = -0.287, p = 0.008) and RBP (? = -44.545, p < 0.001) were independently correlated with eGFR. Conclusion:Age, plasma TNF-?, and 8-OHdG are independent risk factors for renal insufficiency in T2DM patients with normoalbuminuria. Urinary NGAL and RBP can serve as noninvasive biomarkers of normoalbuminuric renal insufficiency in T2DM.

SUBMITTER: Li A

PROVIDER: S-EPMC6766169 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Urinary NGAL and RBP Are Biomarkers of Normoalbuminuric Renal Insufficiency in Type 2 Diabetes Mellitus.

Li Aimei A Yi Bin B Liu Yan Y Wang Jianwen J Dai Qing Q Huang Yuxi Y Li Yan Chun YC Zhang Hao H

Journal of immunology research 20190915

<h4>Objectives</h4>As a screening index of diabetic kidney disease (DKD), urinary albumin/creatine ratio (UACR) is commonly used. However, approximately 23.3%-56.6% of DKD patients with estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m<sup>2</sup> are normoalbuminuric. Thus, urinary biomarkers of nonalbuminuric renal insufficiency in type 2 diabetes mellitus (T2DM) patients are urgently needed.<h4>Methods</h4>This cross-sectional study enrolled 209 T2DM patients with normoalbumi ...[more]

PMID: 31637265

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Project description:BackgroundDiabetic kidney disease is the most common cause of chronic kidney disease (CKD). An early event in diabetic kidney disease is alteration of the glomerular basement membrane and the mesangial expansion. Matrix metalloproteinases (MMP) are a family of endopeptidases responsible for controlling the pathophysiological remodeling of tissues, including renal tissues. MMP-9 in human urine has been proposed as a marker of diabetic nephropathy and urinary tract infections (UTI).MethodsA cross-sectional study was conducted in type 2 diabetes mellitus (T2DM) patients who receive first level medical attention in Mexico. We used ELISA to measure MMP-9 levels in the urine of subjects with T2DM ≥ 18 years of age, who fulfilled the clinical requirements for calculation of glomerular filtration rate (GFR), according to the K/DOQI guide, in an attempt to identify whether MMP-9 levels in T2DM differ in patients with and without renal impairment. Univariate and multivariable analyses were performed in order to identify the association between MMP-9 and renal impairment.ResultsIncluded in the study were 34 (45%) subjects with renal impairment and 42 (55%) without. In the group with renal impairment, 10 subjects corresponded to stages 1-2 and 24 subjects corresponded to stage 3, according to their values of GFR and urinary albumin, following that proposed by the K/DOQI. No differences were found relating to sex, age, having or not having a partner, education, being able to read and write a message and duration of T2DM. Moreover, no differences were found between the groups in terms of weight, height, body mass index, waist size in general and frequency of UTI. In contrast, serum creatinine and urinary albumin were higher in the group with renal impairment, while GFR was greater in the group without renal impairment. Levels of MMP-9 were greater in women compared to men. Through univariate analysis in the general population, the presence of MMP-9 and that of its percentile 90 (P90) P90 were associated with the renal impairment group; however, in patients without UTI, only the presence of MMP-9 was associated with the renal impairment group, and no association was found with its P90. Multivariate analysis revealed an association between MMP-9 and its P90 with renal impairment.DiscussionIt is necessary to validate sensitive and non-invasive biological markers of CKD. We demonstrate that the presence and P90 of urinary MMP-9 are associated with renal impairment in Mexican patients with T2DM. While high levels of MMP-9 were associated to females and UTI, the presence of UTI was not associated with the incidence of renal impairment.

Dataset Information

Urinary NGAL and RBP Are Biomarkers of Normoalbuminuric Renal Insufficiency in Type 2 Diabetes Mellitus.

Publications

Urinary NGAL and RBP Are Biomarkers of Normoalbuminuric Renal Insufficiency in Type 2 Diabetes Mellitus.

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