Proximal Tubule Dysfunction Is Associated with Podocyte Damage Biomarkers Nephrin and Vascular Endothelial Growth Factor in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study

Petrică, Ligia; Vlad, Adrian; Gluhovschi, Gheorghe; Gădălean, Florica; Dumitraşcu, Victor; Gluhovschi, Cristina; Velciov, Silvia; Bob, Flaviu; Vlad, Daliborca; Popescu, Roxana; Milaş, Oana; Ursoniu, Sorin

doi:10.1371/journal.pone.0112538

Cited by 57 publications

(71 citation statements)

References 34 publications

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“…The increased uNep level in neonates with high uCysC concentration indicates that glomerular immaturity and/or injury parallel the degree of tubular immaturity and/or injury in critically ill neonates. Increased levels of glomerular damage markers, which paralleled the elevated levels of tubule dysfunction markers, such as CysC and neutrophil gelatinase-associated lipocalin, have been shown in previous studies [16, 24]. In addition, both the initial urinary levels of nephrin and CysC were significantly higher in AKI than in non-AKI neonates, suggesting that glomerular injuries are induced at the early phase of AKI in critically ill neonates.…”

Section: Discussionsupporting

confidence: 73%

Urinary Nephrin as a Biomarker of Glomerular Maturation and Injury Is Associated with Acute Kidney Injury and Mortality in Critically Ill Neonates

Chen

Wang

et al. 2019

Neonatology

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Background: Nephrin is a key component of the slit diaphragm of the glomerular podocyte, and increased urinary nephrin level may reflect glomerular injury. Objectives: To determine whether urinary nephrin is a useful biomarker of glomerular maturation and injury and whether it is associated with acute kidney injury (AKI) and neonatal intensive care unit (NICU) mortality in critically ill neonates. Methods: Urinary samples were serially collected in 234 neonates during NICU stay for measurements of nephrin, cystatin C (CysC), and albumin. AKI diagnosis was based on neonatal Kidney Disease: Improving Global Outcome (KDIGO) criteria. Results: Of the neonates, 26 developed AKI and 24 died during NICU stay. The independent contributors to the initial urinary nephrin level obtained on the first 24 h admitted to NICU were gestational age (p = 0.004) and initial urinary CysC level (p < 0.001). Both initial (p = 0.037) and peak (p = 0.039) urinary nephrin were significantly associated with AKI, even after controlling for significant covariates, and had an area under the receiver-operating characteristic curve (AUC) of 0.71 and 0.70, respectively, for predicting AKI. At the optimal cutoff value of 0.375 μg/mg urinary creatinine, the initial urinary nephrin displayed sensitivity of 61.5% and specificity of 76.9% for predicting AKI. The AUCs for initial and peak urinary nephrin to predict NICU mortality were 0.81 and 0.83, respectively. Conclusions: Urinary nephrin, which may decrease with increasing glomerular maturity, is significantly associated with increased risk for AKI and NICU mortality even after adjustment for potential confounders. A higher level of urinary nephrin may be independently predictive of AKI and NICU mortality in critically ill neonates.

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Section: Discussionsupporting

confidence: 73%

Urinary Nephrin as a Biomarker of Glomerular Maturation and Injury Is Associated with Acute Kidney Injury and Mortality in Critically Ill Neonates

Chen

Wang

et al. 2019

Neonatology

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“…This observation suggests a potential role of the PT in urinary nephrin and urinary vascular endothelial growth factor processing in early diabetic nephropathy, a fact which could be related to advanced glycation end-products intervention [13]. …”

Section: Discussionmentioning

confidence: 99%

“…Urinary excretion of VEGF may increase even in the normoalbuminuria stage, a fact which suggests that urinary VEGF may be used as a sensitive biomarker in the diagnosis of early DN [13, 14]. …”

Section: Introductionmentioning

confidence: 99%

Urinary podocyte-associated mRNA levels correlate with proximal tubule dysfunction in early diabetic nephropathy of type 2 diabetes mellitus

Petrică

Ursoniu

Gădălean

et al. 2017

Diabetol Metab Syndr

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AimThe study assessed mRNA expression of podocyte-associated molecules in urinary sediments of patients with type 2 diabetes mellitus (DM) in relation to urinary podocytes, biomarkers of podocyte injury and of proximal tubule (PT) dysfunction.MethodsA total of 76 patients with type 2 DM and 20 healthy subjects were enrolled in a cross-sectional study, and assessed concerning urinary podocytes, urinary mRNA of podocyte-associated genes, urinary biomarkers of podocyte damage and of PT dysfunction.ResultsWe found significant differences between urinary mRNA of podocyte-associated molecules in relation with albuminuria stage. In multivariable regression analysis, urinary mRNA of nephrin, podocin, alpha-actinin-4, CD2-associated protein, glomerular epithelial protein 1 (GLEPP1), ADAM 10, and NFκB correlated directly with urinary podocytes, albuminuria, urinary alpha1-microglobulin, urinary kidney-injury molecule-1, nephrinuria, urinary vascular endothelial growth factor, urinary advanced glycation end-products (AGE), and indirectly with eGFR (p < 0.0001, R2 = 0.808; p < 0.0001, R2 = 0.825; p < 0.0001, R2 = 0.805; p < 0.0001, R2 = 0.663; p < 0.0001, R2 = 0.726; p < 0.0001, R2 = 0.720; p < 0.0001, R2 = 0.724).ConclusionsIn patients with type 2 DM there is an association between urinary mRNA of podocyte-associated molecules, biomarkers of podocyte damage, and of PT dysfunction. GLEPP1, ADAM10, and NFκB may be considered additional candidate molecules indicative of early diabetic nephropathy. AGE could be involved in this association.

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“…Moreover, microalbuminuric patients have higher urinary KIM-1 levels than those with normoalbuminuria. 108 Another tubular biomarker with good predictive ability for diabetic kidney disease is urinary L-FABP. Elevated levels of this biomarker were found in normoalbuminuric T1DM patients; urinary L-FABP has a predictive role with respect to the evolution toward microalbuminuria, and of microalbuminuria toward macroalbuminuria.…”

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confidence: 99%

The role of novel biomarkers in predicting diabetic nephropathy: a review

Uwaezuoke

2017

IJNRD

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Diabetic nephropathy (DN) is one of the microvascular complications of the kidney arising commonly from type 1 diabetes mellitus (T1DM), and occasionally from type 2 diabetes mellitus (T2DM). Microalbuminuria serves as an early indicator of DN risk and a predictor of its progression as well as cardiovascular disease risk in both T1DM and T2DM. Although microalbuminuria remains the gold standard for early detection of DN, it is not a sufficiently accurate predictor of DN risk due to some limitations. Thus, there is a paradigm shift to novel biomarkers which would help to predict DN risk early enough and possibly prevent the occurrence of end-stage kidney disease. These new biomarkers have been broadly classified into glomerular biomarkers, tubular biomarkers, biomarkers of inflammation, biomarkers of oxidative stress, and miscellaneous biomarkers which also include podocyte biomarkers, some of which are also considered as tubular and glomerular biomarkers. Although they are potentially useful for the evaluation of DN, current data still preclude the routine clinical use of majority of them. However, their validation using high-quality and large longitudinal studies is of paramount importance, as well as the subsequent development of a biomarker panel which can reliably predict and evaluate this renal microvascular disease. This paper aims to review the predictive role of these biomarkers in the evaluation of DN.

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Proximal Tubule Dysfunction Is Associated with Podocyte Damage Biomarkers Nephrin and Vascular Endothelial Growth Factor in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study

Cited by 57 publications

References 34 publications

Urinary Nephrin as a Biomarker of Glomerular Maturation and Injury Is Associated with Acute Kidney Injury and Mortality in Critically Ill Neonates

Urinary Nephrin as a Biomarker of Glomerular Maturation and Injury Is Associated with Acute Kidney Injury and Mortality in Critically Ill Neonates

Urinary podocyte-associated mRNA levels correlate with proximal tubule dysfunction in early diabetic nephropathy of type 2 diabetes mellitus

The role of novel biomarkers in predicting diabetic nephropathy: a review

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