scholarly journals Urinary Extracellular Vesicles as Biomarkers of Kidney Disease: From Diagnostics to Therapeutics

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 311 ◽  
Author(s):  
In O. Sun ◽  
Lilach O. Lerman
Keyword(s):  
Renal Disease ◽  
Extracellular Vesicles ◽  
Kidney Diseases ◽  
Therapeutic Option ◽  
Kidney Injury ◽  
Human Kidney ◽  
Renal Diseases ◽  
Potential Implication ◽  
Cellular Components

Cell-derived extracellular vesicles (EVs) can be isolated from various body fluids, including urine. Urinary EVs have gained important recognition as potential diagnostic biomarkers in renal disease since their cargo includes nucleic acids, proteins, and other cellular components, which likely mirror the physiological and possibly pathophysiological state of cells along the nephron. Accumulating evidence highlights the feasibility of using EVs as biomarkers for diagnostic, prognostic, and therapeutic purposes in several forms of renal disease, such as acute kidney injury, glomerulonephritis, and renal transplantation. Additionally, exogenous delivery of EVs released in vitro by cells in culture may have salutary benefits for renal diseases. In this review, we introduce recent studies that attempt to identify urinary EVs as candidate biomarkers for human kidney diseases and consider their potential implication as a therapeutic option in key kidney diseases.

scholarly journals Urinary Extracellular Vesicles as Biomarkers of Kidney Disease

2021 ◽  
Vol 96 (1) ◽  
pp. 36-41
Author(s):  
In O Sun
Keyword(s):  
Renal Disease ◽  
Extracellular Vesicles ◽  
Kidney Diseases ◽  
Therapeutic Option ◽  
Extracellular Fluid ◽  
Kidney Injury ◽  
Human Kidney ◽  
Cell Types ◽  
Diagnostic Biomarkers ◽  
Membrane Bound

Extracellular vesicles (EVs) are membrane-bound vesicles produced and released into the extracellular fluid by cells under physiological and stressful conditions. They play a role as intracellular communicators by carrying and delivering biomolecules, such as proteins, lipids, or nucleic acids. Urinary EVs have gained important recognition as potential diagnostic biomarkers in renal disease, as they can originate from diverse cell types, including glomerular podocytes, tubular epithelial cells, or endothelial cells. Accumulating evidence has emphasized the feasibility of using EVs as biomarkers for diagnostic, prognostic, and therapeutic purposes in several forms of renal disease, such as acute kidney injury, glomerulonephritis, and renal transplantation. In this review, we introduce recent studies that attempt to identify urinary EVs as candidate biomarkers for human kidney diseases and consider their potential implications as a therapeutic option in significant kidney diseases.

scholarly journals Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuan-Qiu Cheng ◽  
Yu-Xin Yue ◽  
Hong-Mei Cao ◽  
Wen-Chao Geng ◽  
Lan-Xing Wang ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Self Assembly ◽  
Near Infrared ◽  
Ischemia Reperfusion Injury ◽  
Kidney Diseases ◽  
Therapeutic Option ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
M2 Macrophage ◽  
Novel Strategy

Abstract Background Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). Results In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4β1 and αLβ2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. Conclusion This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs. Graphical Abstract

scholarly journals Assessment of Clinical Spectrum of Renal Diseases in children – A Descriptive Study at Benazir Bhutto Hospital, Rawalpindi

2021 ◽  
Vol 25 (1) ◽  
pp. 42-47
Author(s):  
Maria Shamsher ◽  
Sadaf Ijaz ◽  
Mobeen Tabassum ◽  
Rai Muhammad Asghar
Keyword(s):  
Acute Kidney Injury ◽  
Nephrotic Syndrome ◽  
Renal Disease ◽  
Kidney Diseases ◽  
Heart Diseases ◽  
Health Planning ◽  
Kidney Injury ◽  
Descriptive Study ◽  
Renal Diseases ◽  
Institutional Review

Introduction: Childhood kidney diseases are a frequent presentation. Most of the affected pediatric populations are from under-developed and developing countries. Noting the epidemiology of childhood renal diseases is very important as it helps in health planning, allows for adequate resource allocation, and enables adequate renal services provision. This study aimed to determine the etiological spectrum of renal disease in pediatric patients. Material and Methods: A descriptive study was conducted in Benazir Bhutto Hospital, Rawalpindi over a period of 6 months. Ethical clearance was taken from the institutional review board and written informed consent was administered before enrollment of subject per study criteria. A total of 100 children of both genders, aged up to 12 years with the diagnosis of any renal disease condition were included in the study. Patients having other comorbidities like chronic liver disease and heart diseases were excluded. The study information as age, sex, detailed history, and physical examination, and details of laboratory investigations. Statistical analysis was conducted in SPSS version 20.0. Results: Mean age of patients was 2.1 years. Most patients had a fever, edema, burning micturition, and high blood pressure. In two-thirds of the children RFTs were deranged and 19.0% had positive urinary culture reports. The common kidney diseases were UTI (42.0%), nephrotic syndrome (29.0%), acute kidney injury/ disease (19.0%), and chronic kidney disease (6.0%). Conclusion: UTIs and nephrotic syndrome along with acute kidney injury were the main kidney conditions. Females were more likely to have UTIs whereas nephrotic syndrome was common in male children.  

scholarly journals CD73 Overexpression in Podocytes: A Novel Marker of Podocyte Injury in Human Kidney Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7642
Author(s):  
Zoran V. Popovic ◽  
Felix Bestvater ◽  
Damir Krunic ◽  
Bernhard K. Krämer ◽  
Raoul Bergner ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Membranous Glomerulonephritis ◽  
Human Kidney ◽  
Protective Role ◽  
Control Group ◽  
Podocyte Injury ◽  
Ccr2 Expression ◽  
Cd73 Expression

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, p = 0.0031; Pearson r = −0.4705, p = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.

Antibodies to kidney endothelial cells contribute to a “leaky” glomerular barrier in patients with chronic kidney diseases

2012 ◽  
Vol 302 (7) ◽  
pp. F884-F894 ◽  
Author(s):  
Nidia Maritza Hernandez ◽  
Anna Casselbrant ◽  
Meghnad Joshi ◽  
Bengt R. Johansson ◽  
Suchitra Sumitran-Holgersson
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Kidney Diseases ◽  
Clinical Importance ◽  
Human Kidney ◽  
Cell Permeability ◽  
Chronic Kidney Diseases ◽  
Esrd Patients

Anti-endothelial cell antibodies (AECA) have been reported to cause endothelial dysfunction, but their clinical importance for tissue-specific endothelial cells is not clear. We hypothesized that AECA reactive with human kidney endothelial cells (HKEC) may cause renal endothelial dysfunction in patients with chronic kidney diseases. We report that a higher fraction (56%) of end-stage renal disease (ESRD) patients than healthy controls (5%) have AECA reactive against kidney endothelial cells ( P <0.001). The presence of antibodies was associated with female gender ( P < 0.001), systolic hypertension ( P < 0.01), and elevated TNF-α ( P < 0.05). These antibodies markedly decrease expression of both adherens and tight junction proteins VE-cadherin, claudin-1, and zonula occludens-1 and provoked a rapid increase in cytosolic free Ca2+and rearrangement of actin filaments in HKEC compared with controls. This was followed by an enhancement in protein flux and phosphorylation of VE-cadherin, events associated with augmented endothelial cell permeability. Additionally, kidney biopsies from ESRD patients with AECA but not controls demonstrated a marked decrease in adherens and tight junctions in glomerular endothelium, confirming our in vitro data. In summary, our data demonstrate a causal link between AECA and their capacity to induce alterations in glomerular vascular permeability.

SOX9 is required for kidney fibrosis and activates NAV3 to drive renal myofibroblast function

2021 ◽  
Vol 14 (672) ◽  
pp. eabb4282 ◽  
Author(s):  
Sayyid Raza ◽  
Elliot Jokl ◽  
James Pritchett ◽  
Katherine Martin ◽  
Kim Su ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Actin Polymerization ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Pharmacological Intervention ◽  
Kidney Fibrosis ◽  
Genome Wide ◽  
Vitro Model ◽  
Sustained Activation

Renal fibrosis is a common end point for kidney injury and many chronic kidney diseases. Fibrogenesis depends on the sustained activation of myofibroblasts, which deposit the extracellular matrix that causes progressive scarring and organ failure. Here, we showed that the transcription factor SOX9 was associated with kidney fibrosis in humans and required for experimentally induced kidney fibrosis in mice. From genome-wide analysis, we identified Neuron navigator 3 (NAV3) as acting downstream of SOX9 in kidney fibrosis. NAV3 increased in abundance and colocalized with SOX9 after renal injury in mice, and both SOX9 and NAV3 were present in diseased human kidneys. In an in vitro model of renal pericyte transdifferentiation into myofibroblasts, we demonstrated that NAV3 was required for multiple aspects of fibrogenesis, including actin polymerization linked to cell migration and sustained activation of the mechanosensitive transcription factor YAP1. In summary, our work identifies a SOX9-NAV3-YAP1 axis involved in the progression of kidney fibrosis and points to NAV3 as a potential target for pharmacological intervention.

scholarly journals Insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinases-2: differential expression and secretion in human kidney tubule cells

2017 ◽  
Vol 312 (2) ◽  
pp. F284-F296 ◽  
Author(s):  
David R. Emlet ◽  
Nuria Pastor-Soler ◽  
Allison Marciszyn ◽  
Xiaoyan Wen ◽  
Hernando Gomez ◽  
...  
Keyword(s):  
Cell Culture ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Human Kidney ◽  
Distal Tubule ◽  
Cell Types ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tubule Cell ◽  
Tubule Cells

We have characterized the expression and secretion of the acute kidney injury (AKI) biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in human kidney epithelial cells in primary cell culture and tissue. We established cell culture model systems of primary kidney cells of proximal and distal tubule origin and observed that both proteins are indeed expressed and secreted in both tubule cell types in vitro. However, TIMP-2 is both expressed and secreted preferentially by cells of distal tubule origin, while IGFBP7 is equally expressed across tubule cell types yet preferentially secreted by cells of proximal tubule origin. In human kidney tissue, strong staining of IGFBP7 was seen in the luminal brush-border region of a subset of proximal tubule cells, and TIMP-2 stained intracellularly in distal tubules. Additionally, while some tubular colocalization of both biomarkers was identified with the injury markers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, both biomarkers could also be seen alone, suggesting the possibility for differential mechanistic and/or temporal profiles of regulation of these early AKI biomarkers from known markers of injury. Last, an in vitro model of ischemia-reperfusion demonstrated enhancement of secretion of both markers early after reperfusion. This work provides a rationale for further investigation of these markers for their potential role in the pathogenesis of acute kidney injury.

scholarly journals Extracellular vesicles as immune mediators in response to kidney injury

2018 ◽  
Vol 314 (1) ◽  
pp. F9-F21 ◽  
Author(s):  
Eva Feigerlová ◽  
Shyue-Fang Battaglia-Hsu ◽  
Thierry Hauet ◽  
Jean-Louis Guéant
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Bioactive Molecules ◽  
Renal Diseases ◽  
Cytokine Signaling ◽  
Renal Tubular ◽  
Tissue Recovery

Important progress has been made on cytokine signaling in response to kidney injury in the past decade, especially cytokine signaling mediated by extracellular vesicles (EVs). For example, EVs released by injured renal tubular epithelial cells (TECs) can regulate intercellular communications and influence tissue recovery via both regulating the expression and transferring cytokines, growth factors, as well as other bioactive molecules at the site of injury. The effects of EVs on kidney tissue seem to vary depending on the sources of EVs; however, the literature data are often inconsistent. For example, in rodents EVs derived from mesenchymal stem cells (MSC-EVs) and endothelial progenitor cells (EPC-EVs) can have both beneficial and harmful effects on injured renal tissue. Caution is thus needed in the interpretation of these data as contradictory findings on EVs may not only be related to the origin of EVs, they can also be caused by the different methods used for EV isolation and the physiological and pathological states of the tissues/cells under which they were obtained. Here, we review and discuss our current understanding related to the immunomodulatory function of EVs in renal tubular repair in the hope of encouraging further investigations on mechanisms related to their antiinflammatory and reparative role to better define the therapeutic potential of EVs in renal diseases.

scholarly journals Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwen Yu ◽  
Danli Xie ◽  
Naya Huang ◽  
Qin Zhou
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Circular Rnas ◽  
Specific Expression ◽  
Glomerular Diseases ◽  
Diagnosis And Prognosis

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

Renal medicine

2021 ◽  
pp. 353-382
Author(s):  
Gopesh K. Modi ◽  
Vivekanand Jha
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Rapidly Progressive Glomerulonephritis ◽  
Kidney Injury ◽  
Renal Stones ◽  
Renal Diseases ◽  
Acute Glomerulonephritis ◽  
Glomerular Diseases ◽  
Stage Renal Disease ◽  
End Stage

Assessing renal function, Urinalysis, Proteinuria, Hematuria, Chyluria, Imaging in renal disease, Kidney biopsy, Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), Diabetic Nephropathy, End Stage Renal Disease and Dialysis, Kidney Transplantation, Glomerular diseases, Acute glomerulonephritis, Urinary schistosomiasis (bilharzia), Infections and Kidney Disease, Rapidly Progressive glomerulonephritis, Tubulointerstitial Disease, Urinary Tract Infection, Vesico-ureteric reflux, Renal Stones, Renal Disease in Pregnancy, Renal Artery Stenosis, Renal Mass, Inherited Renal Diseases

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