scholarly journals Role of Macrophages and Related Cytokines in Kidney Disease

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.

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.

Circulating Soluble Fms-Like Tyrosine Kinase in Renal Diseases Other Than Preeclampsia

2021 ◽  
pp. ASN.2020111579
Author(s):  
Theresa Wewers ◽  
Annika Schulz ◽  
Ingo Nolte ◽  
Hermann Pavenstaedt ◽  
Marcus Brand ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Impairment ◽  
Tyrosine Kinase ◽  
Kidney Diseases ◽  
Experimental Studies ◽  
Clinical Findings ◽  
Renal Diseases ◽  
Renal Complication ◽  
Distant Target ◽  
Endothelial Growth Factor

Soluble Fms-like tyrosine kinase (sFlt-1/sVEGFR1) is a natural occurring antagonist of vascular endothelial growth factor (VEGF). Despite being a secreted, soluble protein lacking cytoplasmic and transmembrane domains, sFlt-1 can act locally and be protective against excessive microenvironmental VEGF concentration, or exert autocrine functions independently of VEGF. Circulating sFlt-1 may indiscriminately affect endothelial function and the microvasculature on distant target organs. The clinical significance of excess sFlt-1 in kidney disease was first shown in preeclampsia, a major renal complication of pregnancy. However, circulating sFlt-1 levels appear to be increased in different diseases with varying degrees of renal impairment. Relevant clinical associations between circulating sFlt-1 and severe outcomes (e.g., endothelial dysfunction, renal impairment, cardiovascular disease, and all-cause mortality) have been observed in patients with chronic kidney disease and following kidney transplantation. However, sFlt-1 appears to be protective against renal dysfunction-associated aggravation of atherosclerosis and diabetic nephropathy. Therefore, in this review, we provide an update on sFlt-1 in several kidney diseases other than preeclampsia, discuss clinical findings and experimental studies, and briefly consider its use in clinical practice.

scholarly journals The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

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

<b><i>Background:</i></b> 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<sup>+</sup>) 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. <b><i>Summary:</i></b> 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<sup>+</sup> production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. <b><i>Key Messages:</i></b> 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.

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.

scholarly journals Therapeutic Approaches Targeting Proteostasis in Kidney Disease and Fibrosis

2021 ◽  
Vol 22 (16) ◽  
pp. 8674
Author(s):  
Jia-Huang Chen ◽  
Chia-Hsien Wu ◽  
Chih-Kang Chiang
Keyword(s):  
Kidney Disease ◽  
Er Stress ◽  
Kidney Diseases ◽  
Trigger Factor ◽  
Renal Diseases ◽  
Therapeutic Approaches ◽  
Adaptive Process ◽  
Unfolded Protein ◽  
Molecular Signals ◽  
The Relationship

Pathological insults usually disturb the folding capacity of cellular proteins and lead to the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which leads to so-called “ER stress”. Increasing evidence indicates that ER stress acts as a trigger factor for the development and progression of many kidney diseases. The unfolded protein responses (UPRs), a set of molecular signals that resume proteostasis under ER stress, are thought to restore the adaptive process in chronic kidney disease (CKD) and renal fibrosis. Furthermore, the idea of targeting UPRs for CKD treatment has been well discussed in the past decade. This review summarizes the up-to-date literature regarding studies on the relationship between the UPRs, systemic fibrosis, and renal diseases. We also address the potential therapeutic possibilities of renal diseases based on the modulation of UPRs and ER proteostasis. Finally, we list some of the current UPR modulators and their therapeutic potentials.

scholarly journals The Immunomodulatory Effect of the Gut Microbiota in Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Mingxuan Chi ◽  
Kuai Ma ◽  
Jing Wang ◽  
Zhaolun Ding ◽  
Yunlong Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Renal Diseases

The human gut microbiota is a complex cluster composed of 100 trillion microorganisms, which holds a symbiotic relationship with the host under normal circumstances. Intestinal flora can facilitate the treatment of human metabolic dysfunctions and interact with the intestinal tract, which could influence intestinal tolerance, immunity, and sensitivity to inflammation. In recent years, significant interests have evolved on the association of intestinal microbiota and kidney diseases within the academic circle. Abnormal changes in intestinal microbiota, known as dysbiosis, can affect the integrity of the intestinal barrier, resulting in the bacterial translocation, production, and accumulation of dysbiotic gut-derived metabolites, such as urea, indoxyl sulfate (IS), and p-cresyl sulfate (PCS). These processes lead to the abnormal activation of immune cells; overproduction of antibodies, immune complexes, and inflammatory factors; and inflammatory cell infiltration that can directly or indirectly cause damage to the renal parenchyma. The aim of this review is to summarize the role of intestinal flora in the development and progression of several renal diseases, such as lupus nephritis, chronic kidney disease, diabetic nephropathy, and renal ischemia-reperfusion injury. Further research on these mechanisms should provide insights into the therapeutic potential of regulating intestinal flora and intervening related molecular targets for the abovementioned nephropathy.

scholarly journals SARS-CoV-2 infection in hospitalized pediatric patients with kidney disease

2020 ◽  
Vol 10 (3) ◽  
Author(s):  
Flávia Silveira ◽  
Káthia Zuntini ◽  
Márcia Silveira ◽  
Lohanna Tavares ◽  
Juliana Mendes ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Pediatric Patients ◽  
Kidney Diseases ◽  
Pediatric Population ◽  
Transplant Rejection ◽  
Kidney Injury ◽  
Underlying Disease ◽  
Great Divergence ◽  
Stage 1

OBJECTIVES: This study aims to present the confirmed cases of SARS-CoV-2 infection in pediatric patients with chronic and acute kidney diseases admitted to a tertiary pediatric hospital. METHODS: Descriptive and retrospective observational study with all children hospitalized between March and June 2020 who had, simultaneously, SARS-CoV-2 infection and renal pathologies. Of this total of patients, those who had another underlying disease besides the renal disease were excluded. RESULTS: During the period, nine children with kidney disease were admitted to the hospital and had infection confirmed by the new coronavirus through positive RT-PCR. Regarding the underlying disease, seven had only kidney disease, three of whom had stage 5 chronic kidney disease; one, with stage 1 chronic kidney disease; one, with cortic-sensitive nephrotic syndrome; and two, with acute kidney injury. Two patients in this study had already undergone kidney transplantation, used immunosuppressants and had their doses reduced due to the infectious condition. Only one required oxygen therapy and transfer to the intensive care unit, but was not intubated and returned to the ward within 24 hours. CONCLUSIONS: According to the cases described, the pediatric population with kidney disease, including those using immunosuppressants due to acute transplant rejection, seems to evolve without severe COVID-19, therefore there is no great divergence in relation to the population of the same healthy age group.

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

scholarly journals Stem cell-based treatment of kidney diseases

2020 ◽  
Vol 245 (10) ◽  
pp. 902-910
Author(s):  
Binbin Pan ◽  
Guoping Fan
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Acute Kidney Injury ◽  
Stem Cell ◽  
Kidney Disease ◽  
Cell Therapy ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Great Promise ◽  
Kidney Organoids

Kidney dysfunction, including chronic kidney disease and acute kidney injury, is a globally prevalent health problem. However, treatment regimens are still lacking, especially for conditions involving kidney fibrosis. Stem cells hold great promise in the treatment of chronic kidney disease and acute kidney injury, but success has been hampered by insufficient incorporation of the stem cells in the injured kidney. Thus, new approaches for the restoration of kidney function after acute or chronic injury have been explored. Recently, kidney organoids have emerged as a useful tool in the treatment of kidney diseases. In this review, we discuss the mechanisms and approaches of cell therapy in acute kidney injury and chronic kidney disease, including diabetic kidney disease and lupus nephritis. We also summarize the potential applications of kidney organoids in the treatment of kidney diseases. Impact statement Stem cells hold great promise in regenerative medicine. Pluripotent stem cells have been differentiated into kidney organoids to understand human kidney development and to dissect renal disease mechanisms. Meanwhile, recent studies have explored the treatment of kidney diseases using a variety of cells, including mesenchymal stem cells and renal derivatives. This mini-review discusses the diverse mechanisms underlying current renal disease treatment via stem cell therapy. We postulate that clinical applications of stem cell therapy for kidney diseases can be readily achieved in the near future.

scholarly journals PROTON PUMP INHIBITORS AND THE RISK OF CHRONIC KIDNEY DISEASES: A CRITICAL REVIEW

2020 ◽  
pp. 11-14
Author(s):  
SHAREEF J. ◽  
SRIDHAR S. B. ◽  
SHARIFF A.
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
End Stage Renal Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Stage Renal Disease ◽  
End Stage

Proton pump inhibitors (PPIs) are most widely used medications for acid related gastrointestinal disorders. Accessible evidence based studies suggest that the increased use of PPI is linked to a greater risk of developing kidney diseases. This review aims to determine the association of kidney disease with the use of proton pump inhibitor with various study designs. PubMed, Scopus and Google Scholar databases as well as a reference list of relevant articles were systematically searched for studies by using the following search terms; ‘proton pump inhibitors’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘end stage renal disease’. Both observational and randomized controlled trials (RCTs) exploring the association of PPI use with kidney disease were eligible for inclusion. A total of 8 articles, including 9 studies (n = 794,349 participants) were identified and included in the review. Majority of the studies showed a higher risk of kidney outcomes in patients taking PPIs, with effect higher of acute kidney injury (4-to 6-fold) compared with chronic kidney disease and end stage renal disease (1.5-to 2.5-fold). However, the studies suggest that the strength of evidence is weak and could not prove causation. The risk increased considerably with the use of high dose of PPIs and prolonged duration of exposure necessitates the monitoring of renal function. Exercising vigilance in PPI use and cessation of proton pump inhibitor when there is no clear indication may be a reasonable approach to reduce the population burden of kidney diseases.

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