Toll-Like Receptor as a Potential Biomarker in Renal Diseases

One of the major challenges faced by modern nephrology is the identification of biomarkers associated with histopathological patterns or defined pathogenic mechanisms that may assist in the non-invasive diagnosis of kidney disease, particularly glomerulopathy. The identification of such molecules may allow prognostic subgroups to be established based on the type of disease, thereby predicting response to treatment or disease relapse. Advances in understanding the pathogenesis of diseases, such as membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, IgA (immunoglobulin A) nephropathy, and diabetic nephropathy, along with the progressive development and standardization of plasma and urine proteomics techniques, have facilitated the identification of an increasing number of molecules that may be useful for these purposes. The growing number of studies on the role of TLR (toll-like receptor) receptors in the pathogenesis of kidney disease forces contemporary researchers to reflect on these molecules, which may soon join the group of renal biomarkers and become a helpful tool in the diagnosis of glomerulopathy. In this article, we conducted a thorough review of the literature on the role of TLRs in the pathogenesis of glomerulopathy. The role of TLR receptors as potential marker molecules for the development of neoplastic diseases is emphasized more and more often, as prognostic factors in diseases on several epidemiological backgrounds.

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Role of Chemokine (C–X–C Motif) Ligand 10 (CXCL10) in Renal Diseases

Mediators of Inflammation ◽

10.1155/2020/6194864 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Jie Gao ◽

Lingling Wu ◽

Siyang Wang ◽

Xiangmei Chen

Keyword(s):

Kidney Disease ◽

Mesangial Cells ◽

Human Kidney ◽

Inflammatory Cells ◽

Prognostic Indicator ◽

Renal Diseases ◽

Inflammatory Conditions ◽

Potential Biomarker ◽

Inducible Protein

Chemokine C–X–C ligand 10 (CXCL10), also known as interferon-γ-inducible protein 10 (IP-10), exerts biological function mainly through binding to its specific receptor, CXCR3. Studies have shown that renal resident mesangial cells, renal tubular epithelial cells, podocytes, endothelial cells, and infiltrating inflammatory cells express CXCL10 and CXCR3 under inflammatory conditions. In the last few years, strong experimental and clinical evidence has indicated that CXCL10 is involved in the development of renal diseases through the chemoattraction of inflammatory cells and facilitation of cell growth and angiostatic effects. In addition, CXCL10 has been shown to be a significant biomarker of disease severity, and it can be used as a prognostic indicator for a variety of renal diseases, such as renal allograft dysfunction and lupus nephritis. In this review, we summarize the structures and biological functions of CXCL10 and CXCR3, focusing on the important role of CXCL10 in the pathogenesis of kidney disease, and provide a theoretical basis for CXCL10 as a potential biomarker and therapeutic target in human kidney disease.

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Proteomics and metabolomics studies exploring the pathophysiology of renal dysfunction in autosomal dominant polycystic kidney disease and other ciliopathies

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz121 ◽

2019 ◽

Vol 35 (11) ◽

pp. 1853-1861 ◽

Cited By ~ 1

Author(s):

Miriam Zacchia ◽

Emanuela Marchese ◽

Elena Martina Trani ◽

Marianna Caterino ◽

Giovanna Capolongo ◽

...

Keyword(s):

Kidney Disease ◽

Clinical Signs ◽

Research Area ◽

Clinical Proteomics ◽

Clinical Feature ◽

Physiological Importance ◽

Non Invasive ◽

Human Disorders ◽

Autosomal Dominant Polycystic Kidney

Abstract The primary cilium (PC) was considered as a vestigial organelle with no significant physiological importance, until the discovery that PC perturbation disturbs several signalling pathways and results in the dysfunction of a variety of organs. Genetic studies have demonstrated that mutations affecting PC proteins or its anchoring structure, the basal body, underlie a class of human disorders (known as ciliopathies) characterized by a constellation of clinical signs. Further investigations have demonstrated that the PC is involved in a broad range of biological processes, in both developing and mature tissues. Kidney disease is a common clinical feature of cilia disorders, supporting the hypothesis of a crucial role of the PC in kidney homoeostasis. Clinical proteomics and metabolomics are an expanding research area. Interestingly, the application of these methodologies to the analysis of urine, a biological sample that can be collected in a non-invasive fashion and possibly in large amounts, makes these studies feasible also in patients. The present article describes the most recent proteomic and metabolomic studies exploring kidney dysfunction in the setting of ciliopathies, showing the potential of these methodologies in the elucidation of disease pathophysiology and in the discovery of biomarkers.

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Role of liver biopsy versus non-invasive biomarkers for diagnosis of significant fibrosis and cirrhosis: a web-based survey

Egyptian Liver Journal ◽

10.1186/s43066-021-00166-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mohamed Alboraie ◽

Marwa Khairy ◽

Aisha Elsharkawy ◽

Noha Asem ◽

Mohamed El Kassas ◽

...

Keyword(s):

Liver Cirrhosis ◽

Liver Biopsy ◽

Hepatic Fibrosis ◽

Serum Biomarkers ◽

Response To Treatment ◽

Web Based ◽

Non Invasive ◽

Single Method ◽

Radiological Methods

Abstract Background Liver biopsy is the standard reference for staging hepatic fibrosis. Non-invasive methods for assessment of hepatic fibrosis and cirrhosis are becoming increasingly popular. Objective We aimed at exploring the change in practice regarding the use of liver biopsy and non-invasive methods for staging hepatic fibrosis and cirrhosis among hepatologists. Methods We performed a survey-based study that recruited hepatologists from various Egyptian institutions. Physicians were deemed eligible if they had a degree in internal medicine with hepatology as a subspecialty. We utilized an online-based survey that assessed the acceptability and reliability of liver biopsy, serum biomarkers, and radiological tools for evaluating liver fibrosis and cirrhosis. Results A total of 573 responses were retrieved (response rate = 80.3%). Out of them, 58% were having more than 15 years of experience as a hepatologist. Liver biopsy is still considered the gold standard for assessment of hepatic fibrosis and cirrhosis by 61% of participants. Liver biopsy was accepted by 44% of their patients. 84% reported the need for a more practical alternative to liver biopsy to assess disease progression or response to treatment. 78.34% of participants know serum biomarkers, 84.08% reported that they were acceptable by their patients, 37.79% thought they are reliable. 95.4% were familiar with radiological methods of non-invasive assessment of hepatic fibrosis, 89.1% reported that radiological methods were acceptable by their patients, 62% think that they are reliable and 78% reported they were applicable in clinical practice. Sixty-five percent think that combining non-invasive methods is better than using a single method. Forty percent of participants thought that radiological methods are easier to use for assessment of hepatic fibrosis followed by a combination of non-invasive methods, serum biomarkers, and liver biopsy respectively. Conclusion In conclusion, liver biopsy is still considered the most reliable method for evaluation and staging of liver cirrhosis by hepatologists in Egyptian institutions, despite the modest acceptance by the patients. Nonetheless, non-invasive methods are gaining acceptance by Egyptian physicians and patients, and most of them consider these methods as reliable and applicable tools for predicting the course of liver cirrhosis.

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The Key Role of Epithelial to Mesenchymal Transition (EMT) in Hypertensive Kidney Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20143567 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3567 ◽

Cited By ~ 3

Author(s):

Teresa Seccia ◽

Brasilina Caroccia ◽

Maria Piazza ◽

Gian Paolo Rossi

Keyword(s):

Kidney Disease ◽

Molecular Mechanisms ◽

Epithelial To Mesenchymal Transition ◽

Renal Diseases ◽

Hypertensive Nephropathy ◽

Mesenchymal Transition ◽

Afferent Arterioles ◽

Stage Renal Disease ◽

End Stage

Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT), originally described as a key process for organ development and metastasis budding in cancer, plays a key role in the development of renal fibrosis in several diseases, including hypertensive nephroangiosclerosis. We herein reviewed the concept of EMT and its role in renal diseases, with particular focus on hypertensive kidney disease, the second leading cause of end-stage renal disease after diabetes mellitus. After discussing the pathophysiology of hypertensive nephropathy, the ‘classic’ view of hypertensive nephrosclerosis entailing hyalinization, and sclerosis of interlobular and afferent arterioles, we examined the changes occurring in the glomerulus and tubulo-interstitium and the studies that investigated the role of EMT and its molecular mechanisms in hypertensive kidney disease. Finally, we examined the reasons why some studies failed to provide solid evidence for renal EMT in hypertension.

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Update of ALDH as a Potential Biomarker and Therapeutic Target for AML

BioMed Research International ◽

10.1155/2018/9192104 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Xiangchou Yang ◽

Rongxin Yao ◽

Hong Wang

Keyword(s):

Stem Cells ◽

Residual Disease ◽

Target Therapy ◽

Hematopoietic Stem ◽

Potential Marker ◽

Potential Biomarker ◽

Potential Strategy ◽

New Perspective ◽

Minimal Residual

Studies employing mouse transplantation have illustrated the role of aldehyde dehydrogenase (ALDH) defining hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs). Besides being a molecular marker, ALDH mediates drug resistance in AML, which induces poor prognosis of the patients. In AML patients, either CD34+ALDHbrpopulation or CD34+CD38−ALDHintpopulation was found to denote LSCs and minimal residual disease (MRD). A bunch of reagents targeting ALDH directly or indirectly have been evaluated. ATRA, disulfiram, and dimethyl ampal thiolester (DIMATE) are all shown to be potential candidates to open new perspective for AML treatment. However, inconsistent results have been shown for markers of LSCs, which makes it even more difficult to differentiate LSCs and HSCs. In this review, we elevated the role of ALDH to be a potential marker to define and distinguish HSCs and LSCs and its importance in prognosis and target therapy in AML patients. In addition to immunophenotypical markers, ALDH is also functionally active in defining and distinguishing HSCs and LSCs and offers intracellular protections against cytotoxic drugs. Targeting ALDH may be a potential strategy to improve AML treatment. Additional studies concerning specific targeting ALDH and mechanisms of its roles in LSCs are warranted.

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MiR-4668 as a Novel Potential Biomarker for Eosinophilic Esophagitis

Allergy & Rhinology ◽

10.1177/2152656720953378 ◽

2020 ◽

Vol 11 ◽

pp. 215265672095337

Author(s):

Neeti Bhardwaj ◽

Maria Sena ◽

Gisoo Ghaffari ◽

Faoud Ishmael

Keyword(s):

Eosinophilic Esophagitis ◽

Mirna Expression ◽

Saliva Sample ◽

Allergic Diseases ◽

Response To Therapy ◽

Response To Treatment ◽

Potential Biomarker ◽

Before And After ◽

Interesting Candidate

Introduction Eosinophilic esophagitis (EoE) is a clinico-pathological diagnosis characterized by esophageal dysfunction and eosinophilic infiltration of the esophagus. Demonstration of esophageal eosinophilia (more than 15 eosinophils/hpf) in biopsy specimen obtained by esophagogastroduodenoscopy (EGD) continues to be the gold standard for diagnosis and monitoring of response to therapy. There is a growing necessity for non-invasive biomarkers that can accurately diagnose this condition and assess response to therapy. While microRNAs (miRNA) are being investigated in allergic diseases, including EoE, not many studies have explored the role of salivary miRNAs in EoE. MiR-4668-5p is a particularly interesting candidate, as it is predicted to regulate TGF-beta signaling and has not previously been identified as a target in any allergy disease. We sought to further investigate the role of miR-4668 as a biomarker to characterize and monitor response to treatment with swallowed topical glucocorticoids. Methods After IRB approval, twenty-two adult patients with EoE were randomly enrolled to provide a saliva sample before and after 2 months of swallowed fluticasone therapy. Differences of miRNA expression before and after treatment were analyzed by paired T-test. A significance cutoff of <0.05 was used for all analyses. Results Expression of miR-4668 was higher in EoE vs. non-EoE subjects. The level of miR-4668 decreased in all subjects except one, with a mean fold change 0.49 ± 0.25. There was an association between miRNA expression and number of positive aeroallergens. The miR-4668 high group had a higher number of positive aeroallergen tests, while the miR-4668 low group had a greater number of subjects with drug allergies. Conclusions In this study, we identified that salivary miRNAs may serve as biomarkers to characterize EoE and response to topical corticosteroids. We specifically identified miR-4668 as a novel potential biomarker, which was not previously discovered as a target in EoE or any other allergic disease.

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Role of hypoxia‐inducible factor 1α as a potential biomarker for renal diseases—A systematic review

Cell Biochemistry and Function ◽

10.1002/cbf.3425 ◽

2019 ◽

Vol 37 (6) ◽

pp. 443-451 ◽

Cited By ~ 2

Author(s):

Jéssica Freitas Araújo Encinas ◽

Carlos Henrique Foncesca ◽

Matheus Moreira Perez ◽

Diogo Pimenta Simões ◽

Beatriz Costa Aguiar Alves ◽

...

Keyword(s):

Systematic Review ◽

Hypoxia Inducible Factor ◽

Renal Diseases ◽

Hypoxia Inducible Factor 1Α ◽

Potential Biomarker

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Critical Role for AMPK in Metabolic Disease-Induced Chronic Kidney Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21217994 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7994 ◽

Cited By ~ 1

Author(s):

Florian Juszczak ◽

Nathalie Caron ◽

Anna V. Mathew ◽

Anne-Emilie Declèves

Keyword(s):

Metabolic Disease ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Mammalian Cells ◽

Critical Role ◽

Public Health Problem ◽

Nutrient Sensing ◽

Renal Diseases ◽

Renal Cells

Chronic kidney disease (CKD) is prevalent in 9.1% of the global population and is a significant public health problem associated with increased morbidity and mortality. CKD is associated with highly prevalent physiological and metabolic disturbances such as hypertension, obesity, insulin resistance, cardiovascular disease, and aging, which are also risk factors for CKD pathogenesis and progression. Podocytes and proximal tubular cells of the kidney strongly express AMP-activated protein kinase (AMPK). AMPK plays essential roles in glucose and lipid metabolism, cell survival, growth, and inflammation. Thus, metabolic disease-induced renal diseases like obesity-related and diabetic chronic kidney disease demonstrate dysregulated AMPK in the kidney. Activating AMPK ameliorates the pathological and phenotypical features of both diseases. As a metabolic sensor, AMPK regulates active tubular transport and helps renal cells to survive low energy states. AMPK also exerts a key role in mitochondrial homeostasis and is known to regulate autophagy in mammalian cells. While the nutrient-sensing role of AMPK is critical in determining the fate of renal cells, the role of AMPK in kidney autophagy and mitochondrial quality control leading to pathology in metabolic disease-related CKD is not very clear and needs further investigation. This review highlights the crucial role of AMPK in renal cell dysfunction associated with metabolic diseases and aims to expand therapeutic strategies by understanding the molecular and cellular processes underlying CKD.

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Deprivation and kidney disease—a predictor of poor outcomes

Clinical Kidney Journal ◽

10.1093/ckj/sfz151 ◽

2019 ◽

Vol 13 (2) ◽

pp. 128-132

Author(s):

Greg D Guthrie ◽

Samira Bell

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Renal Disease ◽

Kidney Injury ◽

Renal Diseases ◽

Confounding Factors ◽

Growing Body ◽

Poor Outcomes

Abstract There is a growing body of evidence for the role of deprivation in a broad spectrum of diseases including renal disease. Deprivation has been demonstrated to be associated with poorer outcomes across a range of renal diseases including acute kidney injury (AKI), chronic kidney disease and transplantation. In this issue of Clinical Kidney Journal, Hounkpatin et al. describe the association of socioeconomic deprivation with incidence, mortality and resolution of AKI in a large UK cohort. Investigating deprivation as a factor influencing either incidence or outcome of disease is challenging due to variations in measures of deprivation used and other confounding factors that may be contributing to the observed differences. In this editorial, we review the current literature examining the role of deprivation in renal disease.

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