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 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 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 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.

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.

My Patient with Monoclonal Gammopathy of Undetermined Significance has a Kidney Problem

2017 ◽  
Vol 1 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Nelson Leung
Keyword(s):  
Kidney Disease ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Lymphoproliferative Disorder ◽  
Kidney Diseases ◽  
Organ Damage ◽  
Renal Diseases ◽  
Premalignant Condition ◽  
Definition Of ◽  
Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition signifying the presence of a B-cell lymphoproliferative disorder. By connotation, it should not meet the definition of multiple myeloma, Waldenström macroglobulinemia, or lymphoma. In addition, it cannot be responsible for any end-organ damage. Similar to polyclonal immunoglobulins (Ig), monoclonal gammopathy has been increasingly recognized as an important cause of kidney disease. The recent introduction of the term “monoclonal gammopathy of renal significance” (MGRS) highlights this importance. MGRS is similar to MGUS in which the B-cell lymphoproliferative disorder has not reached a state considered to be malignant, but differentiates itself by the presence of a monoclonal gammopathy related kidney disease. This distinction is important since it separates MGRS, which is not benign, from the MGUS condition, which is benign. It also allows for a better classification of kidney diseases caused by monoclonal gammopathies. There are many renal diseases and lesions that have been identified to be secondary to MGRS. In addition, MGRS-associated renal diseases can mimic polyclonal Ig mediated kidney diseases. Kidney biopsy with immunofluorescence is the key for diagnosing MGRS-related kidney diseases. Once the diagnosis is made, a specific evaluation is needed for the diagnosis and treatment of MGRS-related kidney diseases that differs from the polyclonal Ig counterparts.

scholarly journals It Comes As a Shock

Hypertension ◽  
2020 ◽  
Vol 76 (6) ◽  
pp. 1696-1703
Author(s):  
Nattawat Klomjit ◽  
Amir Lerman ◽  
Lilach O. Lerman
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Energy Levels ◽  
Renal Diseases ◽  
Unique Identifier ◽  
Shockwave Therapy ◽  
Low Intensity ◽  
Proximal Tubular ◽  
Global Health Care ◽  
Endothelial Growth Factors

Chronic kidney disease is a global health care burden, yet clinically-proven treatments are limited. Low-intensity shockwave, which utilizes ≈10% of the energy levels used in clinically indicated shockwave lithotripsy, is a promising technique to ameliorate ischemia and regenerate tissues. It has been demonstrated to improve healing in tissues such as bone, muscle, myocardium, and kidney via several mechanisms, particularly through promoting neovascularization. Low-intensity shockwave stimulates mechanoreceptors located primarily in endothelial and proximal tubular cells and subsequently upregulates vascular endothelial growth factors. This, in turn, promotes angiogenesis and ameliorates renal hypoxia, inflammation, and fibrosis, and ultimately preserves renal function. Furthermore, low-intensity shockwave can stimulate release of homing factors to attract endothelial progenitor or stem cells into injured kidneys for tissue repair. These effects may be beneficial in several kidney disease models, including renal artery stenosis, diabetic kidney disease, and various chronic kidney diseases, although most studies reported to date have been performed in animal models. Because of its low energy intensity, the procedure is relatively tolerable and safe, yet, more clinical studies are needed to establish its efficacy beyond currently existing strategies. Therefore, low-intensity shockwave therapy emerges as an alternative therapeutic approach that may offer a promising noninvasive intervention for treating renal diseases. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02515461; NCT03602807; and NCT03445247.

scholarly journals Hypoxia and Dysregulated Angiogenesis in Kidney Disease

2015 ◽  
Vol 1 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Shinji Tanaka ◽  
Tetsuhiro Tanaka ◽  
Masaomi Nangaku
Keyword(s):  
Kidney Disease ◽  
Adoptive Transfer ◽  
Kidney Diseases ◽  
Hypoxia Inducible Factor ◽  
Kidney Injury ◽  
Angiogenic Factor ◽  
Vegf Expression ◽  
Peritubular Capillaries ◽  
End Stage ◽  
Endothelial Growth Factor

Background: Accumulating evidence has demonstrated that renal hypoxia has a crucial role in the pathogenesis of acute kidney injury (AKI), chronic kidney disease (CKD), and AKI-to-CKD transition, ultimately culminating in end-stage kidney disease. Renal hypoxia in progressive CKD is intricately linked to persisting capillary loss, which is mainly due to dysregulated angiogenesis. Summary: In CKD, hypoxia-inducible factor (HIF) accumulates in the ischemic tubulointerstitium but fails to sufficiently stimulate angiogenic responses, partly because of blunted activation of HIF, which is best exemplified in diabetic kidney disease. In addition, vascular endothelial growth factor (VEGF) expression is downregulated, possibly because injured tubules are not able to express sufficient VEGF and inflammatory circumstances inhibit VEGF expression. The upregulation of antiangiogenic factors and the incompetence of endothelial progenitor cells (EPCs) may also play some roles in the inadequacy of capillary restoration. Administration of VEGF or angiopoietin-1 maintains peritubular capillaries in several kidney diseases; however, administration of a single angiogenic factor may lead to the formation of abnormal vessels and induce inflammation, resulting in worsening of hypoxia and tubulointerstitial fibrosis. HIF stabilization, which aims to achieve the formation of mature and stable vessels by inducing coordinated angiogenesis, is a promising strategy. Given that the effect of systemic HIF activation is highly context-dependent, further studies are needed to elucidate the precise roles of HIF in various kidney diseases. The adoptive transfer of EPCs or mesenchymal stem cells (MSCs) is a fascinating alternative strategy to restore the peritubular capillaries. Key Messages: Suppressed HIF activation and VEGF expression may be responsible for the dysregulated angiogenesis in progressive CKD. Administration of a single angiogenic factor can cause abnormal vessel formation and inflammation, leading to a detrimental result. Although further studies are warranted, HIF stabilization and adoptive transfer of EPCs or MSCs appear to be promising strategies to restore normal capillaries.

scholarly journals Efficacy and safety of sofosbuvir based antiviral therapy for chronic hepatitis C infection in patients with advanced chronic kidney disease

2019 ◽  
Vol 7 (10) ◽  
pp. 3679
Author(s):  
Shahid Rasool ◽  
Ahmad N. Babar ◽  
Muhammad Wasif Baig ◽  
Salman Azhar ◽  
Muhammad Saeed Akhtar
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Kidney Disease ◽  
Chronic Hepatitis C ◽  
Kidney Diseases ◽  
Renal Diseases ◽  
Efficacy And Safety ◽  
Hepatitis C Infection ◽  
Renal Deterioration ◽  
Direct Acting Antiviral

Background: Screening studies for hepatitis C have proved that it is more prevalent in patients with renal diseases. Chronic hepatitis C infection in patients with kidney disease not only accelerates renal deterioration but also adversely effects morbidity and mortality. Availability of direct acting antiviral drugs has revolutionized treatment of hepatitis C even in difficult patients. In advanced kidney diseases, selection of treatment is difficult. Aim of this study was to evaluate the efficacy and safety of Sofosbuvir based DAAs in patients with advanced CKD.Methods: In this Quasi experimental study, CHC patients with or without cirrhosis having advance CKD (eGFR <30 ml/min per 1.73 m2) and/or on dialysis were enrolled. End points of the study were documentation of SVR 12 or discontinuation of therapy. Different regimens of oral DAAs with or without Ribavirin were used.Results: 86 patients with a median age of 53 years were enrolled. 37 patients were on maintenance dialysis and 49 were not on dialysis with eGFR <30 ml/min per 1.73 m2. Virological response was 92.68% at the end of treatment and SVR was achieved by 90.2% twelve weeks after therapy. Insomnia 14%, headache 11% and anemia 7% were main dverse effects. Mean eGFR and creatinine before and after treatment remained the same. Only 2 patients relapsed, both were on dialysis thrice weekly.Conclusions: All Sofosbuvir based regimens used for the treatment of CHC in patients with end stage renal disease are effective and well tolerated. Close follow up is advised to monitor side effects.

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 Connexin 43: a New Therapeutic Target Against Chronic Kidney Disease

2018 ◽  
Vol 49 (3) ◽  
pp. 998-1009 ◽  
Author(s):  
Niki Prakoura ◽  
Panagiotis Kavvadas ◽  
Christos E.  Chadjichristos
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Animal Models ◽  
Renal Disease ◽  
Connexin 43 ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Kidney Diseases ◽  
In Vivo Studies ◽  
Renal Diseases

Chronic kidney disease is an incurable to date pathology with a continuously growing incidence that contributes to the increase of the number of deaths worldwide. With currently no efficient prognostic or therapeutic options being available, the only possibility for treatment of end-stage renal disease is renal replacement therapy through dialysis or transplantation. Understanding the molecular mechanisms participating in the progression of renal diseases and uncovering the pathways implicated will permit the identification of novel and more efficient targets of therapy. Connexin43 was recently identified as a novel player in the development of chronic kidney disease. It was found de novo expressed and/or differentially localized in various renal cell populations during progression of renal disease, indicating an abnormal connexin signaling, both in patients and animal models. Subsequent in vivo studies demonstrated that connexin43 is involved in mediating inflammatory and fibrotic processes contributing to renal damage. Genetic, pharmaco-genetic or peptide-based inhibition of connexin43 in animal models and cell culture systems was successful in preventing the progression of the pathology and preserving the cell phenotypes. This review will summarize the recent advances on connexin43 in the field of kidney diseases and discuss the potential of future connexin43-based therapies against chronic kidney disease.

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