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.

The Emerging Role of Epigenetic Methylation in Kidney Disease

2021 ◽  
Vol 28 ◽  
Author(s):  
Li Wen ◽  
Hong-liu Yang ◽  
Lin Lin ◽  
Liang Ma ◽  
Ping Fu
Keyword(s):  
Dna Methylation ◽  
Kidney Disease ◽  
Histone Methylation ◽  
Kidney Diseases ◽  
Therapeutic Approaches ◽  
Promoter Regions ◽  
Recent Advances ◽  
Epigenetic Methylation

: Kidney disease has complex and multifactorial pathophysiology and pathogenesis. Recent studies have revealed that epigenetic methylation changes, namely DNA methylation, histone methylation and non-histone methylation, are strongly implicated in various forms of kidney diseases. This review provides a perspective on the emerging role of epigenetic methylation in kidney disease, including the effects of DNA methylation in diverse promoter regions, regulation and implication of histone methylation, and recent advances and potential directions related to non-histone methylation. Monitoring or targeting epigenetic methylation has potential to contribute to development of therapeutic approaches for multiple kidney 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.

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 Endoplasmic Reticulum Stress and Unfolded Protein Response in Breast Cancer: The Balance between Apoptosis and Autophagy and Its Role in Drug Resistance

2019 ◽  
Vol 20 (4) ◽  
pp. 857 ◽  
Author(s):  
Lorenza Sisinni ◽  
Michele Pietrafesa ◽  
Silvia Lepore ◽  
Francesca Maddalena ◽  
Valentina Condelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Inflammatory Diseases ◽  
Unfolded Protein ◽  
Chronic Activation ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
The Relationship

The unfolded protein response (UPR) is a stress response activated by the accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER) and its uncontrolled activation is mechanistically responsible for several human pathologies, including metabolic, neurodegenerative, and inflammatory diseases, and cancer. Indeed, ER stress and the downstream UPR activation lead to changes in the levels and activities of key regulators of cell survival and autophagy and this is physiologically finalized to restore metabolic homeostasis with the integration of pro-death or/and pro-survival signals. By contrast, the chronic activation of UPR in cancer cells is widely considered a mechanism of tumor progression. In this review, we focus on the relationship between ER stress, apoptosis, and autophagy in human breast cancer and the interplay between the activation of UPR and resistance to anticancer therapies with the aim to disclose novel therapeutic scenarios. The hypothesis that autophagy and UPR may provide novel molecular targets in human malignancies is discussed.

scholarly journals P0192RELATIONSHIP BETWEEN SERUM HEPCIDIN AND THE PROGRESSION OF CHRONIC KIDNEY DISEASE: KOREAN COHORT STUDY FOR OUTCOME IN PATIENTS WITH CHRONIC KIDNEY DISEASE (KNOW-CKD)

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Su Ah Sung ◽  
Kum Hyun Han ◽  
Jien Lee ◽  
Taehee Lee
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Large Scale ◽  
Hemoglobin Level ◽  
Renal Diseases ◽  
Hepcidin Level ◽  
Replacement Treatment ◽  
Serum Hepcidin ◽  
The Relationship

Abstract Background and Aims Hepcidin plays a central role in iron metabolism. However, few studies have evaluated the relationship between serum hepcidin and the progression of chronic kidney disease (CKD). This study aimed to determine the relationship between serum hepcidin levels and the progression of renal diseases in patients with CKD. Method We reviewed data of 2,016 patients from a large-scale multicenter, prospective study enrolled between 2011 and 2016, who had data regarding the serum hepcidin level, hemoglobin level, iron indices, usage of erythopoiesis-stimulating agents (ESA) or iron, and follow-up of renal events. Renal events were defined as a >50% decrease in kidney function from the baseline values, doubling of the serum creatinine level, or initiation of renal-replacement treatment. Results During a mean 3.6 years, 556 patients developed renal events (27.6%). In multivariate Cox proportional hazard regression analysis adjusted for confounders including kidney function, the hemoglobin level, conventional iron indices, usage of ESA or iron, and other chronic diseases, the hazard of serum hepcidin for renal events was evident in the comparison between only the first and fourth quartiles (hazard ratio 1.603, 95% confidence interval, 1.187-2.163, P = 0.002). In the multivariate penalized spline curve analysis, the relationship between serum hepcidin and renal events was J-shaped, and the renal hazard was particularly evident at a serum hepcidin level ≥60 ng/ml. Conclusion Increased serum hepcidin levels independently predict the progression of CKD in non-dialysis patients with CKD. The potential direct renal hazard of serum hepcidin needs to be confirmed in future randomized controlled trials.

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.

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.

Environmental Toxins and the Kidney

2019 ◽  
pp. 147-154
Author(s):  
Joshua D. King ◽  
Bernard G. Jaar
Keyword(s):  
Heavy Metals ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Food Additives ◽  
Kidney Injury ◽  
Toxic Agent ◽  
Toxic Agents ◽  
Relationship Of ◽  
The Relationship

While many compounds are known to be environmental and occupational nephrotoxins, it is often difficult to define the exact contribution of individual toxins to the development of kidney disease. This chapter discusses the relationship of environmental and occupational toxins to kidney diseases, explores the pathogenesis of nephrotoxicity of specific agents, stresses the importance of removal from the toxic agent(s), and describes considerations relevant to medical treatment of selected toxic exposures causative of kidney disease. A number of individual nephrotoxins such as heavy metals, silica compounds, herbal medications, and food additives are discussed in more detail, as is the epidemiology of chronic kidney disease and acute kidney injury due to environmental and occupational toxins. Options for treatment and controversies pertaining to the therapy of toxic agents causative of kidney disease are explored, particularly the role of chelation of heavy metals.

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.

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