scholarly journals NGAL and Metabolomics: The Single Biomarker to Reveal the Metabolome Alterations in Kidney Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
A. Noto ◽  
F. Cibecchini ◽  
V. Fanos ◽  
M. Mussap
Keyword(s):  
Structural Changes ◽  
Biomarker Discovery ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Functional Change ◽  
Therapeutic Interventions ◽  
Cellular Damage ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Cellular Processes ◽  
And Function

Conditions affecting kidney structure and function can be considered acute or chronic, depending on their duration. Acute kidney injury (AKI) is one of a number of acute kidney diseases and consists of an abrupt decline in kidney function after an injury leading to functional and structural changes. The widespread availability of enabling technologies has accelerated the rate of novel biomarker discovery for kidney injury. The introduction of novel biomarkers in clinical practice will lead to better preventative and therapeutic interventions and to improve outcomes of critically ill patients. A number of biomarkers of functional change and cellular damage are under evaluation for early diagnosis, risk assessment, and prognosis of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as the most promising biomarker of kidney injury; this protein can be measured by commercially available methods in whole blood, plasma, serum, and urine. Concomitantly, metabolomics appears to be a snapshot of the chemical fingerprints identifying specific cellular processes. In this paper, we describe the role of NGAL for managing AKI and the potential benefits deriving from the combined clinical use of urine NGAL and metabolomics in kidney disease.

scholarly journals Reduced O-GlcNAcylation and tubular hypoxia contribute to the antifibrotic effect of SGLT2 inhibitor dapagliflozin in the diabetic kidney

2020 ◽  
Vol 318 (4) ◽  
pp. F1017-F1029 ◽  
Author(s):  
Judit Hodrea ◽  
Dora B. Balogh ◽  
Adam Hosszu ◽  
Lilla Lenart ◽  
Balazs Besztercei ◽  
...  
Keyword(s):  
High Glucose ◽  
Kidney Diseases ◽  
Combined Treatment ◽  
Hypoxia Inducible Factor ◽  
Sglt2 Inhibitor ◽  
Kidney Injury ◽  
Diabetic Kidney ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Male Wistar Rats ◽  
Kidney Injury Molecule 1

Diabetic kidney disease is a worldwide epidemic, and therapies are incomplete. Clinical data suggest that improved renal outcomes by Na+-glucose cotransporter 2 inhibitor (SGLT2i) are partly beyond their antihyperglycemic effects; however, the mechanisms are still elusive. Here, we investigated the effect of the SGLT2i dapagliflozin (DAPA) in the prevention of elevated O-GlcNAcylation and tubular hypoxia as contributors of renal fibrosis. Type 1 diabetes was induced by streptozotocin in adult male Wistar rats. After the onset of diabetes, rats were treated for 6 wk with DAPA or DAPA combined with losartan (LOS). The effect of hyperglycemia was tested in HK-2 cells kept under normal or high glucose conditions. To test the effect of hypoxia, cells were kept in 1% O2 for 2 h. Cells were treated with DAPA or DAPA combined with LOS. DAPA slowed the loss of renal function, mitigated renal tubular injury markers (kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin), and reduced tubulointerstitial fibrosis. DAPA diminished high glucose-induced protein O-GlcNAcylation and moderated the tubular response to hypoxia through the hypoxia-inducible factor pathway. DAPA alone was as effective as combined treatment with LOS in all outcome parameters. These data highlight the role of ameliorated O-GlcNAcylation and diminished tubular hypoxia as important benefits of SGLT2i treatment. Our results support the link between glucose toxicity, tubular hypoxia, and fibrosis, a vicious trio that could be targeted by SGLT2i in kidney diseases of other origins as well.

scholarly journals iTRAQ-based comparative proteomics analysis reveals specific urinary biomarkers for various kidney diseases

2019 ◽  
Author(s):  
Juan Jin ◽  
Jianguang Gong ◽  
Li Zhao ◽  
Yiwen Li ◽  
Qiang He
Keyword(s):  
Biomarker Discovery ◽  
Bioinformatics Analysis ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Urinary Proteins ◽  
Proteomics Analysis ◽  
Kegg Pathway Analysis ◽  
Go Enrichment ◽  
Differentially Abundant Proteins

Abstract Background Urinary proteomics has been extensively applied to investigate renal diseases including acute kidney injury (AKI), chronic kidney disease (CKD), IgA nephropathy (IgAN) and diabetic CKD. However, differential urinary proteome studies have not been reported for multiple diseases. The present study was aimed to explore early clinical diagnosis biomarkers for patients with AKI, AKI+CKD, diabetic CKD, non-diabetic CKD with IgAN and non-diabetic CKD without IgAN. Methods Differentially expressed proteins (DEPs) were screened by iTRAQ labeling and 2-D LC-MS/MS. Bioinformatics analysis was performed by subsequent GO enrichment and KEGG pathway analysis. DEPs were authenticated by ELISA assay. Results 156, 156, 286, 187 and 184 differentially abundant proteins were identified in patients with AKI, AKI+CKD, diabetic CKD, and non-diabetic CKD with or without IgAN. Comparative analysis indicated that 34, 35 and 17 unique DEPs were found in AKI, AKI+CKD and CKD samples, respectively. 91 and 14 specific DEPs were screened out in diabetic CKD and non-diabetic CKD. In comparison with Non-diabetic CKD with IgAN (38 DEPs), 47 unique urinary proteins were found in Non-diabetic CKD without IgAN. Among these DEPs, urinary SAA1 and HGFAC were only unregulated in AKI and Non-diabetic CKD without IgAN implying that they might be employed as the potential indicators of the two diseases. C5, APOC1 and Reg3A upregulation was not exclusively expressed in each disease which suggested that they could not be used for biomarker to distinguish one disease from the other. Conclusion Collectively, this research contributes to the urinary biomarker discovery from multiple renal diseases.

Autophagy in Kidney Disease

2020 ◽  
Vol 82 (1) ◽  
pp. 297-322 ◽  
Author(s):  
Mary E. Choi
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Therapeutic Benefit ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Kidney Diseases ◽  
Cellular Processes ◽  
Autophagy Pathway

Autophagy is a cellular homeostatic program for the turnover of cellular organelles and proteins, in which double-membraned vesicles (autophagosomes) sequester cytoplasmic cargos, which are subsequently delivered to the lysosome for degradation. Emerging evidence implicates autophagy as an important modulator of human disease. Macroautophagy and selective autophagy (e.g., mitophagy, aggrephagy) can influence cellular processes, including cell death, inflammation, and immune responses, and thereby exert both adaptive and maladaptive roles in disease pathogenesis. Autophagy has been implicated in acute kidney injury, which can arise in response to nephrotoxins, sepsis, and ischemia/reperfusion, and in chronic kidney diseases. The latter includes comorbidities of diabetes and recent evidence for chronic obstructive pulmonary disease–associated kidney injury. Roles of autophagy in polycystic kidney disease and kidney cancer have also been described. Targeting the autophagy pathway may have therapeutic benefit in the treatment of kidney disorders.

scholarly journals SERUM NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) AS A PREDICTIVE BIOMARKER OF KIDNEY INJURY IN RENAL TRANSPLANTED PATIENTS and CHRONIC KIDNEY DISEASE

2017 ◽  
Vol 9 (6) ◽  
pp. 59
Author(s):  
Zainab A.a. Al-shamma ◽  
Nahla Ghanim Alklyali ◽  
Intesar Yousif Alani
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Color Change ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
High Serum ◽  
Post Transplantation ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Healthy Control ◽  
Neutrophil Gelatinase

Objective: Neutrophil gelatinase-associated lipocalin has emerged as a promising biomarker of kidney injury better than creatinine to early predict the acute kidney injury in both chronic kidney diseases and early diagnosis of kidney allograft dysfunction.Methods: Neutrophil gelatinase-associated lipocalin was evaluated as a new biomarker for acute renal injury in 69 patients were divided in two groups chronic kidney disease patients (stage5), (n=34), and renal transplant patients, (n=35) comparing with apparently healthy control (n= 35) of matching age and weight. Neutrophil gelatinase-associated lipocalin, hsCRP and Cystatin-C were measured by enzyme-linked immune sorbent assay which is included first incubating the test serum in an antigen-coated polystyrene plate, then enzyme labelled anti-immunoglobulin is added and the enzyme then remaining in plate after washing provides a measure of the amount of specific antibody in the serum and in the final step a substance is added that the enzyme can convert to some detectable signal, most commonly a color change in a chemical substrate.Results: There was a significant increase in serum NGAL of renal transplantation patients, and CKD patients (stage5) than in healthy control subjects (455±145 ng/ml vs. 296.4±83.5 ng/ml 486±153 ng/ml vs296. 4±83.5 ng/ml) respectively. A high serum Neutrophil gelatinase-associated lipocalin is noted in renal transplanted patients after one month, then after six months (480±188ng/ml vs. 409±78ng/ml). There was a significant negative correlation between serum Neutrophil gelatinase-associated lipocalin in renal transplanted patients, and chronic kidney disease patients (stage 5) with an estimated glomerular filtration rate (p<0.05).Conclusion: Serum neutrophil gelatinase-associated lipocalin seems to be an early predictor of kidney injury and post-transplantation management, including dialysis and grafting function of the kidney.

scholarly journals Aquaporins in Renal Diseases

2019 ◽  
Vol 20 (2) ◽  
pp. 366 ◽  
Author(s):  
Jinzhao He ◽  
Baoxue Yang
Keyword(s):  
Kidney Diseases ◽  
Kidney Injury ◽  
Concentration Function ◽  
Urine Concentration ◽  
Renal Diseases ◽  
Chronic Kidney Diseases ◽  
Transmembrane Channels ◽  
Normal Urine ◽  
And Function ◽  
Urine Concentrating Ability

Aquaporins (AQPs) are a family of highly selective transmembrane channels that mainly transport water across the cell and some facilitate low-molecular-weight solutes. Eight AQPs, including AQP1, AQP2, AQP3, AQP4, AQP5, AQP6, AQP7, and AQP11, are expressed in different segments and various cells in the kidney to maintain normal urine concentration function. AQP2 is critical in regulating urine concentrating ability. The expression and function of AQP2 are regulated by a series of transcriptional factors and post-transcriptional phosphorylation, ubiquitination, and glycosylation. Mutation or functional deficiency of AQP2 leads to severe nephrogenic diabetes insipidus. Studies with animal models show AQPs are related to acute kidney injury and various chronic kidney diseases, such as diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma. Experimental data suggest ideal prospects for AQPs as biomarkers and therapeutic targets in clinic. This review article mainly focuses on recent advances in studying AQPs in renal diseases.

scholarly journals 2140

2017 ◽  
Vol 1 (S1) ◽  
pp. 12-12
Author(s):  
Pinaki Sarder ◽  
Rabi Yacoub ◽  
John E. Tomaszewski
Keyword(s):  
Structural Changes ◽  
Computational Study ◽  
Kidney Diseases ◽  
Quantitative Information ◽  
Renal Tissue ◽  
Therapeutic Interventions ◽  
Theoretical Physics ◽  
Computational Pipeline ◽  
Disease Trajectory ◽  
Digital Biomarkers

OBJECTIVES/SPECIFIC AIMS: (i) Digitally quantify pathologically relevant glomerular microcompartmental structures in murine renal tissue histopathology images. (ii) Digitally model disease trajectory in a mouse model of diabetic nephropathy (DN). METHODS/STUDY POPULATION: We have developed a computational pipeline for glomerular structural compartmentalization based on Gabor filtering and multiresolution community detection (MCD). The MCD method employs improved, efficient optimization of a Potts model Hamiltonian, adopted from theoretical physics, modeling interacting electron spins. The method is parameter-free and capable of simultaneously selecting relevant structure at all biologically relevant scales. It can segment glomerular compartments from a large image containing hundreds of glomeruli in seconds for quantification—which is not possible manually. We will analyze the performance of our computational pipeline in healthy and streptozotocin induced DN mice using renal tissue images, and model the structural distributions of automatically quantified glomerular features as a function of DN progression. The performance of this structural-disease model will be compared with existing visual quantification methods used by pathologists in the clinic. RESULTS/ANTICIPATED RESULTS: Computational modeling will reveal digital biomarkers for early proteinuria in DN, able to predict disease trajectory with greater precision and accuracy than manual inspection alone. DISCUSSION/SIGNIFICANCE OF IMPACT: Automated detection of microscopic structural changes in renal tissue will eventually lead to objective, standardized diagnosis, reflecting cost savings for DN through discovery of digital biomarkers hidden within numerical structural distributions. This computational study will pave the path for the creation of new digital tools which provide clinicians invaluable quantitative information about expected patient disease trajectory, enabling earlier clinical predictions and development of early therapeutic interventions for kidney diseases.

scholarly journals Macrophage Phenotype in Kidney Injury and Repair

2015 ◽  
Vol 1 (2) ◽  
pp. 138-146 ◽  
Author(s):  
Xiao-Ming Meng ◽  
Patrick Ming-Kuen Tang ◽  
Jun Li ◽  
Hui Yao Lan
Keyword(s):  
Renal Injury ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
Chronic Kidney Diseases ◽  
Chronic Kidney Injury ◽  
Injury And Repair ◽  
And Function

Background: Glomerular and interstitial macrophage infiltration is a feature for both the acute and chronic kidney diseases. Macrophages have been shown to play a diverse role in kidney injury and repair. Thus, macrophages may be a key cell type in acute and chronic kidney injury and repair. Summary and Key Messages: During renal inflammation, circulating monocytes are recruited and then become activated and polarized. By adapting to the local microenvironment, macrophages can differentiate into different phenotypes and function as a double-bladed sword in different stages of kidney disease. In general, M1 macrophages play a pathogenic role in boosting inflammatory renal injury, whereas M2 macrophages exert an anti-inflammatory and wound healing (or profibrotic) role during renal repair. In this review, we highlight the phenotypic polarization of macrophages in renal diseases and dissect their distinct functions in renal injury and repair processes, respectively. Moreover, the current understanding of regulatory mechanisms on the phenotypic switch and macrophage-related therapy are also intensively discussed.

scholarly journals Dual Actions of A2A and A3 Adenosine Receptor Ligand Prevents Obstruction-Induced Kidney Fibrosis in Mice

2021 ◽  
Vol 22 (11) ◽  
pp. 5667
Author(s):  
Eun Seon Pak ◽  
Lak Shin Jeong ◽  
Xiyan Hou ◽  
Sushil K. Tripathi ◽  
Jiyoun Lee ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Tubulointerstitial Fibrosis ◽  
Cellular Damage ◽  
Kidney Fibrosis ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
A3 Adenosine Receptor ◽  
Kidney Morphology ◽  
Neutrophil Gelatinase ◽  
First Time ◽  
And Oxidative Stress

Kidney fibrosis is the final outcome of chronic kidney disease (CKD). Adenosine plays a significant role in protection against cellular damage by activating four subtypes of adenosine receptors (ARs), A1AR, A2AAR, A2BAR, and A3AR. A2AAR agonists protect against inflammation, and A3AR antagonists effectively inhibit the formation of fibrosis. Here, we showed for the first time that LJ-4459, a newly synthesized dual-acting ligand that is an A2AAR agonist and an A3AR antagonist, prevents the progression of tubulointerstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed on 6-week-old male C57BL/6 mice. LJ-4459 (1 and 10 mg/kg) was orally administered for 7 days, started at 1 day before UUO surgery. Pretreatment with LJ-4459 improved kidney morphology and prevented the progression of tubular injury as shown by decreases in urinary kidney injury molecular-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) excretion. Obstruction-induced tubulointerstitial fibrosis was attenuated by LJ-4459, as shown by a decrease in fibrotic protein expression in the kidney. LJ-4459 also inhibited inflammation and oxidative stress in the obstructed kidney, with reduced macrophage infiltration, reduced levels of pro-inflammatory cytokines, as well as reduced levels of reactive oxygen species (ROS). These data demonstrate that LJ-4459 has potential as a therapeutic agent against the progression of tubulointerstitial fibrosis.

scholarly journals Mitochondrial DNA-Mediated Inflammation in Acute Kidney Injury and Chronic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Lini Jin ◽  
Binfeng Yu ◽  
Ines Armando ◽  
Fei Han
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Mitochondrial Dna ◽  
Kidney Disease ◽  
Inflammatory Responses ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Inflammasome Activation ◽  
Mtdna Copy Number ◽  
And Function

The integrity and function of mitochondria are essential for normal kidney physiology. Mitochondrial DNA (mtDNA) has been widely a concern in recent years because its abnormalities may result in disruption of aerobic respiration, cellular dysfunction, and even cell death. Particularly, aberrant mtDNA copy number (mtDNA-CN) is associated with the development of acute kidney injury and chronic kidney disease, and urinary mtDNA-CN shows the potential to be a promising indicator for clinical diagnosis and evaluation of kidney function. Several lines of evidence suggest that mtDNA may also trigger innate immunity, leading to kidney inflammation and fibrosis. In mechanism, mtDNA can be released into the cytoplasm under cell stress and recognized by multiple DNA-sensing mechanisms, including Toll-like receptor 9 (TLR9), cytosolic cGAS-stimulator of interferon genes (STING) signaling, and inflammasome activation, which then mediate downstream inflammatory cascades. In this review, we summarize the characteristics of these mtDNA-sensing pathways mediating inflammatory responses and their role in the pathogenesis of acute kidney injury, nondiabetic chronic kidney disease, and diabetic kidney disease. In addition, we highlight targeting of mtDNA-mediated inflammatory pathways as a novel therapeutic target for these kidney diseases.

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