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

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.

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Renal medicine

10.1093/med/9780198810858.003.0008 ◽

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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Use of Lipid-Modifying Agents for the Treatment of Glomerular Diseases

Journal of Personalized Medicine ◽

10.3390/jpm11080820 ◽

2021 ◽

Vol 11 (8) ◽

pp. 820

Author(s):

Mengyuan Ge ◽

Sandra Merscher ◽

Alessia Fornoni

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Recent Progress ◽

Kidney Diseases ◽

Kidney Injury ◽

Glomerular Diseases ◽

Intracellular Lipids ◽

Lipid Modifying Agents ◽

Made In

Although dyslipidemia is associated with chronic kidney disease (CKD), it is more common in nephrotic syndrome (NS), and guidelines for the management of hyperlipidemia in NS are largely opinion-based. In addition to the role of circulating lipids, an increasing number of studies suggest that intrarenal lipids contribute to the progression of glomerular diseases, indicating that proteinuric kidney diseases may be a form of “fatty kidney disease” and that reducing intracellular lipids could represent a new therapeutic approach to slow the progression of CKD. In this review, we summarize recent progress made in the utilization of lipid-modifying agents to lower renal parenchymal lipid accumulation and to prevent or reduce kidney injury. The agents mentioned in this review are categorized according to their specific targets, but they may also regulate other lipid-relevant pathways.

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Renal involvement in pediatric patients with COVID-19: an up-to-date

Current Pediatric Reviews ◽

10.2174/1573396317666210924121550 ◽

2021 ◽

Vol 17 ◽

Author(s):

Yuri Márcio Campos ◽

André Luís Vieira Drumond ◽

Mariane de Matos Gamonal ◽

Milena Pereira Parreira ◽

Ana Cristina Simões e Silva

Keyword(s):

At Risk ◽

Acute Kidney Injury ◽

Pediatric Patients ◽

Chronic Renal Disease ◽

Kidney Diseases ◽

Renal Involvement ◽

Kidney Injury ◽

Renal Diseases ◽

Glomerular Diseases ◽

Report Data

Background: In pediatric patients, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has been mostly associated with mild symptoms. However, as in adults, renal involvement has been reported in children and adolescents with Coronavirus Disease 2019 (COVID-19). Objective: This review aimed to report data about renal involvement in pediatric COVID-9. The focuses were on the pathophysiology of acute kidney injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated (PIMS-TS) with SARS-CoV-2 and the possible impact of SARS-CoV-2 infection upon kidney function, as well as data concerning patients with previous kidney diseases, including Nephrotic Syndrome and Chronic Renal Disease. The implications for COVID-19 outcome in pediatric patients were also discussed. Methods: This integrative review searched for articles on renal involvement in pediatric COVID-19 patients. The databases evaluated were PubMed and Scopus. Results: The emergence of PIMS-TS with SARS-CoV-2 has shown that pediatric patients are at risk of severe COVID-19, with multi-organ involvement and dysfunction. In addition to intense inflammation, several systems are affected in this syndrome, collectively creating a combination of factors that results in acute kidney injury. Several studies have proposed that kidney cells, including the podocytes, might be at risk of direct infection by SARS-CoV-2, as high levels of ACE2, the virus receptor, are expressed on the membrane of such cells. Some cases of glomerular diseases triggered by SARS-CoV-2 infection and relapses of previous renal diseases have been reported. Conclusion: Further studies are necessary to establish risk factors for renal involvement in pediatric COVID-19 and to predict disease outcome.

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The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

American Journal of Nephrology ◽

10.1159/000519811 ◽

2021 ◽

pp. 1-17

Author(s):

Hai Ning Wee ◽

Jian-Jun Liu ◽

Jianhong Ching ◽

Jean-Paul Kovalik ◽

Su Chi Lim

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Animal Models ◽

Kidney Diseases ◽

Kidney Injury ◽

Kynurenine Pathway ◽

T Cell Subsets ◽

Renal Diseases ◽

Tryptophan Degradation

Background: The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. Summary: This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD+ production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. Key Messages: KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.

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Circular RNAs Serve as Novel Biomarkers and Therapeutic Targets in Cancers

Current Gene Therapy ◽

10.2174/1566523218666181109142756 ◽

2019 ◽

Vol 19 (2) ◽

pp. 125-133 ◽

Cited By ~ 12

Author(s):

Shuai Fang ◽

Jinchang Pan ◽

Chengwei Zhou ◽

Hui Tian ◽

Jinxian He ◽

...

Keyword(s):

Therapeutic Targets ◽

Cancer Gene Therapy ◽

Circular Rnas ◽

Specific Expression ◽

Closed Loops ◽

Diagnosis And Prognosis ◽

Cell Tissue ◽

Novel Biomarkers ◽

Non Coding Rnas ◽

Cancer Tissues

Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) that structurally form closed loops without 5'-end cap and 3'-end poly(A) tail unlike linear RNAs. CircRNAs are widely present in eukaryotic cells with the capabilities of structural stability, high abundance and cell- /tissue-specific expression. A growing body of researches suggest that the dysregulated circRNAs are intimately relevant to the occurrence and development of cancer. In this review, we mainly discuss the differentially expressed circRNAs in cancer tissues, plasma and exosomes, which makes it possible for clinicians to use certain circRNAs as novel biomarkers for cancer diagnosis and prognosis. In particular, we primarily focus on circRNAs as potential therapeutic targets, which will provide promising applications in cancer gene therapy.

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Urinary microRNA in kidney disease: utility and roles

AJP Renal Physiology ◽

10.1152/ajprenal.00368.2018 ◽

2019 ◽

Vol 316 (5) ◽

pp. F785-F793 ◽

Cited By ~ 3

Author(s):

In O. Sun ◽

Lilach O. Lerman

Keyword(s):

Kidney Disease ◽

Biological Fluids ◽

Expression Patterns ◽

Systemic Circulation ◽

Renal Tissue ◽

Renal Physiology ◽

Renal Diseases ◽

Specific Expression ◽

Disease States ◽

Cell Proliferation And Differentiation

MicroRNAs (miRNAs) are small, noncoding single-stranded RNA oligonucleotides that modulate physiological and pathological processes by modulating target gene expression. Many miRNAs display tissue-specific expression patterns, the dysregulation of which has been associated with various disease states, including kidney disease. Mounting evidence implicates miRNAs in various biological processes, such as cell proliferation and differentiation and cancer. Because miRNAs are relatively stable in tissue and biological fluids, particularly when carried by extracellular vesicles, changes in their levels may reflect the development of human disease. Urinary miRNAs originate from primary kidney and urinary tract cells, cells infiltrating the renal tissue and shed in the urine, or the systemic circulation. Although their validity as biomarkers for kidney disease has not been fully established, studies have been applying analysis of miRNAs in the urine in an attempt to detect and monitor acute and chronic renal diseases. Because appreciation of the significance of miRNAs in the renal field is on the rise, an understanding of miRNA pathways that regulate renal physiology and pathophysiology is becoming critically important. This review aims to summarize new data obtained in this field of research. It is hoped that new developments in the use of miRNAs as biomarkers and/or therapy will help manage and contain kidney disease in affected subjects.

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Renal Diseases Associated with Hematologic Malignancies and Thymoma in the Absence of Renal Monoclonal Immunoglobulin Deposits

Diagnostics ◽

10.3390/diagnostics11040710 ◽

2021 ◽

Vol 11 (4) ◽

pp. 710

Author(s):

Antoine Morel ◽

Marie-Sophie Meuleman ◽

Anissa Moktefi ◽

Vincent Audard

Keyword(s):

Kidney Diseases ◽

Specific Treatment ◽

Kidney Injury ◽

Myeloproliferative Disorders ◽

Hematologic Malignancies ◽

Lymphocytic Leukemia ◽

Renal Diseases ◽

Diagnostic Strategy ◽

Monoclonal Immunoglobulin ◽

Glomerular Diseases

In addition to kidney diseases characterized by the precipitation and deposition of overproduced monoclonal immunoglobulin and kidney damage due to chemotherapy agents, a broad spectrum of renal lesions may be found in patients with hematologic malignancies. Glomerular diseases, in the form of paraneoplastic glomerulopathies and acute kidney injury with various degrees of proteinuria due to specific lymphomatous interstitial and/or glomerular infiltration, are two major renal complications observed in the lymphoid disorder setting. However, other hematologic neoplasms, including chronic lymphocytic leukemia, thymoma, myeloproliferative disorders, Castleman disease and hemophagocytic syndrome, have also been associated with the development of kidney lesions. These renal disorders require prompt recognition by the clinician, due to the need to implement specific treatment, depending on the chemotherapy regimen, to decrease the risk of subsequent chronic kidney disease. In the context of renal disease related to hematologic malignancies, renal biopsy remains crucial for accurate pathological diagnosis, with the aim of optimizing medical care for these patients. In this review, we provide an update on the epidemiology, clinical presentation, pathophysiological processes and diagnostic strategy for kidney diseases associated with hematologic malignancies outside the spectrum of monoclonal gammopathy of renal significance.

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Role of Macrophages and Related Cytokines in Kidney Disease

Frontiers in Medicine ◽

10.3389/fmed.2021.688060 ◽

2021 ◽

Vol 8 ◽

Author(s):

Elena Cantero-Navarro ◽

Sandra Rayego-Mateos ◽

Macarena Orejudo ◽

Lucía Tejedor-Santamaria ◽

Antonio Tejera-Muñoz ◽

...

Keyword(s):

Kidney Disease ◽

Immune Cells ◽

Kidney Diseases ◽

Experimental Studies ◽

Kidney Injury ◽

Chronic Inflammatory Disease ◽

Renal Diseases ◽

Circulating Cells ◽

Functional Homolog ◽

Nephron Loss

Inflammation is a key characteristic of kidney disease, but this immune response is two-faced. In the acute phase of kidney injury, there is an activation of the immune cells to fight against the insult, contributing to kidney repair and regeneration. However, in chronic kidney diseases (CKD), immune cells that infiltrate the kidney play a deleterious role, actively participating in disease progression, and contributing to nephron loss and fibrosis. Importantly, CKD is a chronic inflammatory disease. In early CKD stages, patients present sub-clinical inflammation, activation of immune circulating cells and therefore, anti-inflammatory strategies have been proposed as a common therapeutic target for renal diseases. Recent studies have highlighted the plasticity of immune cells and the complexity of their functions. Among immune cells, monocytes/macrophages play an important role in all steps of kidney injury. However, the phenotype characterization between human and mice immune cells showed different markers; therefore the extrapolation of experimental studies in mice could not reflect human renal diseases. Here we will review the current information about the characteristics of different macrophage phenotypes, mainly focused on macrophage-related cytokines, with special attention to the chemokine CCL18, and its murine functional homolog CCL8, and the macrophage marker CD163, and their role in kidney pathology.

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Mitochondrial dysfunction in the pathophysiology of renal diseases

AJP Renal Physiology ◽

10.1152/ajprenal.00571.2013 ◽

2014 ◽

Vol 306 (4) ◽

pp. F367-F378 ◽

Cited By ~ 183

Author(s):

Ruochen Che ◽

Yanggang Yuan ◽

Songming Huang ◽

Aihua Zhang

Keyword(s):

Mitochondrial Dna ◽

Mitochondrial Dysfunction ◽

Nuclear Dna ◽

Kidney Diseases ◽

Mitochondrial Dynamics ◽

Critical Role ◽

Kidney Injury ◽

High Energy ◽

Renal Diseases ◽

Glomerular Diseases

Mitochondrial dysfunction has gained recognition as a contributing factor in many diseases. The kidney is a kind of organ with high energy demand, rich in mitochondria. As such, mitochondrial dysfunction in the kidney plays a critical role in the pathogenesis of kidney diseases. Despite the recognized importance mitochondria play in the pathogenesis of the diseases, there is limited understanding of various aspects of mitochondrial biology. This review examines the physiology and pathophysiology of mitochondria. It begins by discussing mitochondrial structure, mitochondrial DNA, mitochondrial reactive oxygen species production, mitochondrial dynamics, and mitophagy, before turning to inherited mitochondrial cytopathies in kidneys (inherited or sporadic mitochondrial DNA or nuclear DNA mutations in genes that affect mitochondrial function). Glomerular diseases, tubular defects, and other renal diseases are then discussed. Next, acquired mitochondrial dysfunction in kidney diseases is discussed, emphasizing the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease and acute kidney injury, as their prevalence is increasing. Finally, it summarizes the possible beneficial effects of mitochondrial-targeted therapeutic agents for treatment of mitochondrial dysfunction-mediated kidney injury-genetic therapies, antioxidants, thiazolidinediones, sirtuins, and resveratrol-as mitochondrial-based drugs may offer potential treatments for renal diseases.

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The Spectrum of Children's Kidney Diseases—2403 Renal Biopsy-proven Cases from a Single Centre in China between 1999 and 2019

10.21203/rs.3.rs-140880/v1 ◽

2021 ◽

Author(s):

Li-Jun Jiang ◽

Xue Zhao ◽

Zhi-Yan Dou ◽

Zan-Hua Rong ◽

Lin Yang

Keyword(s):

Kidney Disease ◽

Alport Syndrome ◽

Kidney Diseases ◽

Membranous Glomerulonephritis ◽

Proliferative Glomerulonephritis ◽

Renal Diseases ◽

Glomerular Diseases ◽

Common Cause ◽

Thin Basement Membrane Nephropathy ◽

Renal Biopsies

Abstract Background: This study aimed to investigate the clinical and pathological characteristics and the profile of and temporal changes in glomerular diseases in 2403 paediatric renal biopsies from 1999 to 2019.Methods: Renal biopsies performed on children aged ≤18 years between 1999 and 2019 were analysed at our centre. We analysed the clinical and histological characteristics, distribution of paediatric renal diseases with various clinical presentations, and changes in the pattern of kidney disease during the study period.Results: The most common primary glomerular disease was IgA nephropathy (IgAN) (24.3%), followed by minimal change disease (MCD) (15.3%) and membranous glomerulonephritis (MN) (13.1%). Henoch-Schonlein purpura nephritis (HSPN) (18.1%) and lupus nephritis (LN) (7.2%) were the most frequently recorded secondary glomerular diseases. Alport syndrome and thin basement membrane nephropathy (TBMN) were the most common inherited glomerular diseases, accounting for 1.2% and 0.6% of the total glomerular diseases in children, respectively. The number of boys with IgAN, MCD and IgM nephropathy (IgMN) was significantly higher than that of girls, while the number of girls with MN and LN was significantly higher than that of boys. The frequencies of MCD, MN, IgMN and endocapillary proliferative glomerulonephritis (EnPGN) in the 13-18-year-old group were significantly higher than those in the 0-12-year-old group, while the frequencies of IgAN, mesangial proliferative glomerulonephritis (MsPGN) and focal proliferative glomerulonephritis (FPGN) were lower than those in the 0-12-year-old group. The ratio of Alport syndrome and TBMN in the 0-12-year-old group was significantly higher than that in the 13-18-year-old group. The proportion of patients with MCD and MN in 2010-2019 was significantly higher than that in 1999-2009, while the ratio of IgAN, MsPGN, IgMN, EnPGN, membranoproliferative glomerulonephritis (MPGN), HSPN and HBV-associated glomerulonephritis (HBV-GN) decreased. MCD (28.5%) was the most common cause of nephrotic syndrome (NS). In children with haematuria and proteinuria, HSPN (38.8%) and IgAN (36.9%) were more common than other glomerular diseases. IgAN (39.4%) was the most common cause of AKI. Sclerosing glomerulonephritis (SGN) (21.1%) was the main cause of progressive chronic kidney disease (CKD).Conclusions: Glomerular diseases in children were related to sex and age. From 1999 to 2019, the spectrum of children's kidney disease in our centre changed significantly.

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