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 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.

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 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.

scholarly journals Occupational chronic kidney disease: differential diagnosis and expert evaluation

2019 ◽  
Vol 4 (2) ◽  
pp. 32-37
Author(s):  
Strizhakov LA ◽  
Babanov SA ◽  
Garipova RV ◽  
Arkhipov EV ◽  
Lebedeva MV ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Differential Diagnosis ◽  
Kidney Disease ◽  
Environmental Factors ◽  
Prevalence Rate ◽  
Kidney Diseases ◽  
Renal Diseases ◽  
Expert Evaluation ◽  
Production Environment ◽  
Chemical Agents

This review focuses on kidney diseases resulting from exposure to chemical agents in production environment; special attention is given to diseases' classification, prevalence rate, specificity of clinical representation and diagnosis. The frequency of occupational renal diseases is underestimated due to poor manifestation of the symptoms and the influence of environmental factors; thus this problem requires further investigation.

scholarly journals Eosinophilia and Risk of Incident End Stage Kidney Disease

2019 ◽  
Author(s):  
Anam Tariq ◽  
Keisuke Okamato ◽  
Azka Tariq ◽  
Avi Z. Rosenberg ◽  
Karim Soliman ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Biopsy ◽  
Kidney Diseases ◽  
Renal Diseases ◽  
Peripheral Eosinophilia ◽  
End Stage Kidney Disease ◽  
Blood Leukocytes ◽  
Tissue Eosinophilia ◽  
Biopsy Tissue ◽  
End Stage

Abstract Background Eosinophils in kidney disease are poorly understood and are often incidental findings on kidney biopsy. Eosinophilia in blood and renal biopsy tissue is associated with a host of immune and non-immune kidney diseases. The significance of eosinophilia in renal diseases has not been well addressed. We evaluated the incidence of peripheral eosinophilia (>4% of blood leukocytes) with biopsy tissue eosinophilia and their association with end-stage-kidney-disease (ESKD). Methods A nested case-control of patients who underwent kidney biopsies at Johns Hopkins Hospital and Medical University of South Carolina from 2004-2018 were included in the study. From the 616 eligible patients, 178 patients were identified through the registry of kidney biopsies as 18 years or older without missing biopsy reports or hematology results. Controls had no ESKD at the time of case definition and assembled using incident density sampling, matched on age and sex. The association of peripheral eosinophilia (>4% of peripheral blood leukocytes) with the risk of progression to ESKD was evaluated using conditional logistic model after adjusting for clinical demographics. Results Among 178 patients, 65 (37%) had peripheral eosinophilia and 113 (63%) had no eosinophilia. Compared to patients without eosinophilia, patients with peripheral eosinophilia were notably male and had a higher serum creatinine at the time of their biopsy. Peripheral eosinophilia was significantly associated with higher risk of ESKD (OR 6.2 [1.6, 23.8]) adjusted for patient demographics including hypertension, proteinuria, race and eGFR at the time of kidney biopsy. Peripheral eosinophilia had a significant linear association with tissue eosinophilia, 22 (SD 20) per high power field (hpf) in 4-10% peripheral eosinophilia, 19 (SD 18) hpf in >10% eosinophilia and 3 (SD 7) hpf in no eosinophilia (P <0.001). Conclusions Peripheral eosinophilia is an independent predictor of tissue eosinophilia and subsequent progression to ESKD. Peripheral eosinophilia may be an early biomarker for underlying inflammation and disease, but further studies to investigate this clinical association are warranted.

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