Role of Urinary Neutrophil Gelatinase–Associated Lipocalin for Predicting the Severity of Renal Functions in Patients With Autosomal-Dominant Polycystic Kidney Disease

Vareesangthip, K.; Limwongse, Chanin; Reesukumal, Kanit

doi:10.1016/j.transproceed.2017.03.061

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) is frequently proposed as an early marker for renal progression in ADPKD adult patients. Similar to a previous study conducted in the adult ADPKD population by Vareesangthip et al (29), we found no significant difference in uNGAL values between the two groups. This finding is in contrast to our hypothesis and other observations in adults (17, 20), reporting higher uNGAL values when compared to controls.…”

Section: Discussionsupporting

confidence: 91%

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Early Urinary Biomarkers in Pediatric Autosomal Dominant Polycystic Kidney Disease (ADPKD): No Evidence in the Interest of Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL)

et al. 2019

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Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is increasingly diagnosed during childhood by the presence of renal cysts in patients with a positive familial history. No curative treatment is available and early detection and diagnosis confronts pediatricians with the lack of early markers to decide whether to introduce renal-protective agents and prevent the progression of renal failure. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a tubular protein that has been recently proposed as an early biomarker of renal impairment in the ADPKD adult population. Methods: Urinary NGAL (uNGAL) levels were measured in 15 ADPKD children and compared with 15 age and gender matched controls using parametric, non-parametric, and Bayesian statistics. We also tested the association of uNGAL levels with markers of disease progression, such as proteinuria, albuminuria, blood pressure, and Total Kidney Volume (TKV) using correlation analysis. TKV was calculated by ultrasound, using the ellipsoid method. Results: No difference in mean uNGAL levels was observed between groups (ADPKD: 26.36 ng/ml; Controls: 27.24 ng/ml; P = 0.96). Moreover, no correlation was found between uNGAL and proteinuria ( P = 0.51), albuminuria ( P = 0.69), TKV ( P = 0.68), or mean arterial pressure ( P = 0.90). By contrast, TKV was positively correlated with proteinuria ( P = 0.04), albuminuria ( P = 0.001), and mean arterial pressure ( P = 0.03). Conclusion: uNGAL did not confirm its superiority as a marker of disease progression in a pediatric ADPKD population. In the contrary, TKV appears to be an easy measurable variable and may be promising as a surrogate marker to follow ADPKD progression in children.

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Section: Discussionsupporting

confidence: 91%

“…However, as hypothesized by the authors, these results may be due to the lack of communication between the cystic space and the urinary collection system (30). On the other hand, several studies showed a positive correlation between uNGAL values and a worsening of renal function or creatininemia (17, 21, 29).…”

Section: Discussionmentioning

confidence: 99%

Early Urinary Biomarkers in Pediatric Autosomal Dominant Polycystic Kidney Disease (ADPKD): No Evidence in the Interest of Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL)

et al. 2019

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“…Since an increase in the NGAL level of diabetic nephropathy occurs in the early stage of kidney injury, even in patients with normoalbuminuria, NGAL can play a role as a predictor of renal failure [ 66 ]. The role of NGAL in patients with autosomal dominant policystic kidney disease (ADPKD) has also been studied [ 130 , 131 , 132 ]. NGAL concentrations elevate with the impairment of renal function and with an increase in the number of cysts.…”

Section: Ngal In Kidney Diseasesmentioning

confidence: 99%

The Review of Current Knowledge on Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Romejko¹,

Markowska²,

Niemczyk³

2023

IJMS

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Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein that is secreted mostly by immune cells such as neutrophils, macrophages, and dendritic cells. Its production is stimulated in response to inflammation. The concentrations of NGAL can be measured in plasma, urine, and biological fluids such as peritoneal effluent. NGAL is known mainly as a biomarker of acute kidney injury and is released after tubular damage and during renal regeneration processes. NGAL is also elevated in chronic kidney disease and dialysis patients. It may play a role as a predictor of the progression of renal function decreases with complications and mortality due to kidney failure. NGAL is also useful in the diagnostic processes of cardiovascular diseases. It is highly expressed in injured heart tissue and atherosclerostic plaque; its serum concentrations correlate with the severity of heart failure and coronary artery disease. NGAL increases inflammatory states and its levels rise in arterial hypertension, obesity, diabetes, and metabolic complications such as insulin resistance, and is also involved in carcinogenesis. In this review, we present the current knowledge on NGAL and its involvement in different pathologies, especially its role in renal and cardiovascular diseases.

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“…In most clinical cases, ADPKD patients show higher levels of NGAL in their urine than normal people [19,[47][48][49]. The ADPKD mouse model used in this study also has higher NGAL and NGAL-R expression levels [31].…”

Section: Discussionmentioning

confidence: 89%

Secreted Neutrophil Gelatinase-Associated Lipocalin Shows Stronger Ability to Inhibit Cyst Enlargement of ADPKD Cells Compared with Nonsecreted Form

Chuang

Jeng

Wang

et al. 2022

Cells

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Polycystic kidney disease (PKD) is one of the most common inherited diseases and is characterized by the development of fluid-filled cysts along multiple segments of the nephron. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of PKD, which is caused by mutations in either PKD1 or PKD2 genes that encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. As ADPKD progresses, cysts enlarge and disrupt normal kidney architecture, eventually leading to kidney failure. Our previous study showed that overexpression of exogenous kidney-specific neutrophil gelatinase-associated lipocalin (NGAL) reduced cyst progression and prolonged the lifespan of ADPKD mice (Pkd1L3/L3, 2L3 for short). In this study, we attempted to explore the underlying mechanism of reduced cyst progression in the presence of NGAL using immortalized 2L3 cells. The results of MTT and BrdU incorporation assays showed that recombinant mouse NGAL (mNGAL) protein significantly decreased the viability and proliferation of 2L3 cells. Flow cytometry and western blot analyses showed that mNGAL inhibited activation of the ERK and AKT pathways and induced apoptosis and autophagy in 2L3 cells. In addition, a 3D cell culture platform was established to identify cyst progression in 2L3 cells and showed that mNGAL significantly inhibited cyst enlargement in 2L3 cells. Overexpression of secreted mNGAL (pN + LS) and nonsecreted mNGAL (pN − LS) repressed cell proliferation and cyst enlargement in 2L3 cells and had effects on markers involved in proliferation, apoptosis, and autophagy. However, secreted mNGAL had a more pronounced and consistent effect than that of nonsecreted form. These results reveal that secreted mNGAL has stronger ability to inhibit cyst enlargement of ADPKD cells than that of nonsecreted form. These findings could help to identify strategies for the future clinical treatment of ADPKD.

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Role of Urinary Neutrophil Gelatinase–Associated Lipocalin for Predicting the Severity of Renal Functions in Patients With Autosomal-Dominant Polycystic Kidney Disease

Cited by 5 publications

References 29 publications

Early Urinary Biomarkers in Pediatric Autosomal Dominant Polycystic Kidney Disease (ADPKD): No Evidence in the Interest of Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL)

Early Urinary Biomarkers in Pediatric Autosomal Dominant Polycystic Kidney Disease (ADPKD): No Evidence in the Interest of Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL)

The Review of Current Knowledge on Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Secreted Neutrophil Gelatinase-Associated Lipocalin Shows Stronger Ability to Inhibit Cyst Enlargement of ADPKD Cells Compared with Nonsecreted Form

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