Kidney Diseases最新文献

{"title":"The Growth Factors: Potential Biomarkers and Therapeutic Targets in Kidney Diseases.","authors":"Wei Tang,&nbsp;Yufeng Zhang,&nbsp;Sijia Cui,&nbsp;Fan Yi","doi":"10.1159/000526208","DOIUrl":"https://doi.org/10.1159/000526208","url":null,"abstract":"<p><strong>Background: </strong>Kidney diseases are a prevalent health problem worldwide. Although substantial progress has been made in understanding the pathophysiology of kidney disease, currently there is no satisfactory clinical treatment available to prevent or treat kidney disease. Therefore, strategies to establish early diagnosis, identify the key molecules, and develop novel therapeutic interventions to slow the progression of kidney diseases and reduce their complications are encouraged.</p><p><strong>Summary: </strong>The growth factors play a crucial role in the development of kidney diseases. The altered levels of growth factors are usually detected in circulation and urine in the disease course. A growing body of studies has suggested that growth factors, receptors, and related regulators are promising biomarkers for the diagnosis and/or prognosis and potential therapeutic targets for the treatment of kidney diseases. In this review, we summarize recent advances in the potential applications of growth factors for diagnostic biomarkers and therapeutic targets in kidney diseases and highlight their performances in clinical trials.</p><p><strong>Key messages: </strong>Most diagnostic and therapeutic strategies targeting growth factors are still far from clinical implementation. The better understanding of growth factor-regulated pathophysiology and the progress of new intervention approaches are expected to facilitate the clinical translation of growth factor-based diagnosis and therapy of kidney diseases.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"8 5","pages":"368-380"},"PeriodicalIF":3.7,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/94/23/kdd-0008-0368.PMC9710479.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35207965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SENP3 Aggravates Renal Tubular Epithelial Cell Apoptosis in Lipopolysaccharide-Induced Acute Kidney Injury via deSUMOylation of Drp1.","authors":"Lirui Wang,&nbsp;Jiangtao Li,&nbsp;Chen Yu","doi":"10.1159/000525308","DOIUrl":"https://doi.org/10.1159/000525308","url":null,"abstract":"<p><strong>Background: </strong>Sepsis causes acute kidney injury (AKI) in critically ill patients, although the mechanisms underlying the pathophysiology are not fully understood. SUMO-specific proteases 3 (SENP3), a member of the deSUMOylating enzyme family, is known as a redox sensor and could regulate multiple cellular signaling pathways. However, the role of SENP3 in septic AKI remains unclear.</p><p><strong>Objectives: </strong>The purpose of this study was to investigate the role of SENP3 in lipopolysaccharide (LPS)-induced AKI model.</p><p><strong>Methods: </strong>C57BL/6 mice were given intraperitoneal injection of LPS (10 mg/kg). NRK-52E cells were treated with LPS in vitro. The SENP3 protein expression was analyzed by Western blotting. The levels of reactive oxygen species (ROS) in cells were measured using DCFH-DA. SENP3-siRNA or SENP3-plasmid was, respectively, transfected into NRK-52E cells to knock down or overexpress the SENP3 expression. Western blotting was performed to analyze the protein expression of cleaved caspase 3, cytochrome c, and dynamin-related protein 1 (Drp1). The mitochondrial membrane potential was measured using JC-1 assay kit. Co-immunoprecipitation was used to determine the interaction of Drp1 and SMUO2/3.</p><p><strong>Results: </strong>SENP3 protein expression was obviously increased in renal tissues from the mouse model of LPS-induced AKI. Accordingly, SENP3 expression was upregulated in NRK-52E cells treated with LPS in a ROS-dependent manner in vitro. Knockdown of SENP3 dramatically ameliorated LPS-induced apoptosis of NRK-52E cells, whereas overexpression of SENP3 further aggravated LPS-induced apoptosis of NRK-52E cells. Mechanistically, SENP3 triggered Drp1 recruitment to mitochondria by increasing the deSUMOylation of Drp1.</p><p><strong>Conclusion: </strong>SENP3 aggravated renal tubular epithelial cell apoptosis in LPS-induced AKI via Drp1 deSUMOylation manner.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"8 5","pages":"424-435"},"PeriodicalIF":3.7,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a7/0f/kdd-0008-0424.PMC9710481.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35207964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Should More Patients with Kidney Failure Bring Treatment Home? What We Have Learned from COVID-19.","authors":"Xueqing Yu,&nbsp;Vivekanand Jha,&nbsp;Hidetomo Nakamoto","doi":"10.1159/000525046","DOIUrl":"https://doi.org/10.1159/000525046","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic is challenging healthcare systems worldwide and has placed hospitals and healthcare providers (HCPs) at the center of a global crisis. Disruptions to hospital priorities, and limitations placed on the mobility of societies, have contributed to changes in the way HCPs and patients view and access dialysis for kidney failure, including which dialysis modality is preferred.</p><p><strong>Summary: </strong>This article explores the dialysis experience within the COVID-19 pandemic environment in the Asia Pacific region and presents evidence that peritoneal dialysis (PD) provides benefits to patients, HCPs, and health systems. As the number of people infected with COVID-19 has increased, the advantages of PD as a dialysis modality for limiting the spread of COVID-19 infection has been recognized.</p><p><strong>Key message: </strong>The utility of PD has been demonstrated during the COVID-19 pandemic; thus, ensuring that the usage of PD is maintained and increased in a post-pandemic future is key. Such a scenario could enhance our ability to care for patients without interruption in circumstances of unforeseen obstacles and supports the ability of healthcare systems and patients to overcome barriers to dialysis access.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":" ","pages":"357-367"},"PeriodicalIF":3.7,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/8a/kdd-0008-0357.PMC9372457.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40723160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Immune-Related Genetic and Epigenetic Alterations with Lupus Nephritis.","authors":"Xiaole Mei,&nbsp;Hui Jin,&nbsp;Ming Zhao,&nbsp;Qianjin Lu","doi":"10.1159/000524937","DOIUrl":"https://doi.org/10.1159/000524937","url":null,"abstract":"<p><strong>Background: </strong>The familial clustering phenomenon together with environmental influences indicates the presence of a genetic and epigenetic predisposition to systematic lupus erythematosus (SLE). Interestingly, regarding lupus nephritis (LN), the worst complication of SLE, mortality, and morbidity were not consistent with SLE in relation to sexuality and ethnicity.</p><p><strong>Summary: </strong>Genetic and epigenetic alterations in LN include genes and noncoding RNAs that are involved in antigen-presenting, complements, immune cell infiltration, interferon pathways, and so on. Once genetic or epigenetic change occurs alone or simultaneously, they will promote the formation of immune complexes with autoantibodies that target various autoantigens, which results in inflammatory cytokines and autoreactive immune cells colonizing renal tissues and contributing to LN.</p><p><strong>Key messages: </strong>Making additional checks for immunopathology-related heredity and epigenetic factors may lead to a more holistic perspective of LN.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"8 4","pages":"286-296"},"PeriodicalIF":3.7,"publicationDate":"2022-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/6d/kdd-0008-0286.PMC9386430.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33483210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"suPAR: An Inflammatory Mediator for Kidneys.","authors":"Yashwanth Reddy Sudhini,&nbsp;Changli Wei,&nbsp;Jochen Reiser","doi":"10.1159/000524965","DOIUrl":"https://doi.org/10.1159/000524965","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is a common feature of many kidney diseases. The implicated inflammatory mediators and their underlying molecular mechanisms however are often not clear.</p><p><strong>Summary: </strong>suPAR is the soluble form of urokinase-type plasminogen activator receptor (uPAR), associated with inflammation and immune activation. It has evolved into a unique circulating kidney disease factor over the last 10 years. In particular, suPAR has multiple looks due to enzymatic cleavage and alternative transcriptional splicing of the uPAR gene. Most recently, suPAR has emerged as a systemic mediator for COVID-19 infection, associated with lung as well as kidney dysfunction. Like membrane-bound uPAR, suPAR could interact with integrins (e.g., αvβ3 integrin) on podocytes, providing the molecular basis for some glomerular kidney diseases. In addition, there have been numerous studies suggesting that suPAR connects acute kidney injury to chronic kidney disease as a special kidney risk factor. Moreover, the implication of circulating suPAR levels in kidney transplantation and plasmapheresis not only indicates its relevance in monitoring for recurrence but also implies suPAR as a possible therapeutic target. In fact, the therapeutic concept of manipulating suPAR function has been evidenced in several kidney disease experimental models.</p><p><strong>Key messages: </strong>The last 10 years of research has established suPAR as a unique inflammatory mediator for kidneys. While open questions remain and deserve additional studies, modulating suPAR function may represent a promising novel therapeutic strategy for kidney disease.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":" ","pages":"265-274"},"PeriodicalIF":3.7,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/02/kdd-0008-0265.PMC9251480.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40601575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning-Based Model Significantly Improves Diagnostic Performance for Assessing Renal Histopathology in Lupus Glomerulonephritis.","authors":"Luping Shen,&nbsp;Wenyi Sun,&nbsp;Qixiang Zhang,&nbsp;Mengru Wei,&nbsp;Huanke Xu,&nbsp;Xuan Luo,&nbsp;Guangji Wang,&nbsp;Fang Zhou","doi":"10.1159/000524880","DOIUrl":"https://doi.org/10.1159/000524880","url":null,"abstract":"<p><strong>Background: </strong>Assessment of glomerular lesions and structures plays an essential role in understanding the pathological diagnosis of glomerulonephritis and prognostic evaluation of many kidney diseases. Renal pathophysiological assessment requires novel high-throughput tools to conduct quantitative, unbiased, and reproducible analyses representing a central readout. Deep learning may be an effective tool for glomerulonephritis pathological analysis.</p><p><strong>Methods: </strong>We developed a murine renal pathological system (MRPS) model to objectify the pathological evaluation via the deep learning method on whole-slide image (WSI) segmentation and feature extraction. A convolutional neural network model was used for accurate segmentation of glomeruli and glomerular cells of periodic acid-Schiff-stained kidney tissue from healthy and lupus nephritis mice. To achieve a quantitative evaluation, we subsequently filtered five independent predictors as image biomarkers from all features and developed a formula for the scoring model.</p><p><strong>Results: </strong>Perimeter, shape factor, minimum internal diameter, minimum caliper diameter, and number of objects were identified as independent predictors and were included in the establishment of the MRPS. The MRPS showed a positive correlation with renal score (<i>r</i> = 0.480, <i>p</i> < 0.001) and obtained great diagnostic performance in discriminating different score bands (Obuchowski index, 0.842 [95% confidence interval: 0.759, 0.925]), with an area under the curve of 0.78-0.98, sensitivity of 58-93%, specificity of 72-100%, and accuracy of 74-94%.</p><p><strong>Conclusion: </strong>Our MRPS for quantitative assessment of renal WSIs from MRL/lpr lupus nephritis mice enables accurate histopathological analyses with high reproducibility, which may serve as a useful tool for glomerulonephritis diagnosis and prognosis evaluation.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"8 4","pages":"347-356"},"PeriodicalIF":3.7,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/47/kdd-0008-0347.PMC9386416.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33483207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activated Platelets, the Booster of Chronic Kidney Disease and Cardiovascular Complications.","authors":"Shuiqin Gong,&nbsp;Chenyu Wang,&nbsp;Jiachuan Xiong,&nbsp;Jinghong Zhao,&nbsp;Ke Yang","doi":"10.1159/000525090","DOIUrl":"https://doi.org/10.1159/000525090","url":null,"abstract":"<p><p>Background Chronic kidney disease (CKD) has become a global public health problem nowadays. As cardiovascular diseases (CVDs) are the primary cause of death in advanced CKD patients, much attention has been paid to resolving their cardiovascular complications. However, managing CKD and cardiovascular complications is still a big challenge for nephrologists, as satisfactory treatments are still lacking. Platelets, the second most abundant cells in the blood, are the major participants of hemostasis, thrombosis, and wound healing. In recent years, platelets have been reported in various physiological and pathological processes, including CKD and CKD-related CVDs.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"8 4","pages":"297-307"},"PeriodicalIF":3.7,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3b/4f/kdd-0008-0297.PMC9386414.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33483211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Membranous Nephropathy by Disulfiram through Inhibition of Podocyte Pyroptosis.","authors":"Daoyuan Lv,&nbsp;Song Jiang,&nbsp;Mingchao Zhang,&nbsp;Xiaodong Zhu,&nbsp;Fan Yang,&nbsp;Hui Wang,&nbsp;Shen Li,&nbsp;Feng Liu,&nbsp;Caihong Zeng,&nbsp;Weisong Qin,&nbsp;Limin Li,&nbsp;Zhihong Liu","doi":"10.1159/000524164","DOIUrl":"https://doi.org/10.1159/000524164","url":null,"abstract":"<p><strong>Introduction: </strong>Membranous nephropathy (MN) is a common chronic kidney disease in adults and a major challenge of clinical practice for its treatment. Despite major advances, since the discovery of the phospholipase A2 receptor as the major autoantigen of podocytes in MN, the mechanisms leading to glomerular damage remain elusive. Pyroptosis, a newly discovered type of programed necrotic cell death mainly mediated by gasdermin, was found to be responsible for podocyte injury in MN in our recent work.</p><p><strong>Objectives: </strong>The aim of this study was to explore the therapeutic effect of an FDA-approved drug, disulfiram (DSF), in the treatment of MN by inhibiting pyroptosis.</p><p><strong>Methods and results: </strong>DSF significantly alleviated C3a/C5a-induced podocyte injury in vitro and renal lesions in passive Heymann nephritis (PHN) rats, as reflected by the decreased percentage of propidium iodide staining podocytes, decreased lactate dehydrogenase release from cultured podocytes and improvement in 24-h urine protein, serum albumin, serum creatinine, abnormal alterations of podocyte injury markers Desmin and WT-1 and podocyte foot process fusion in PHN rats. The protective effect of DSF on podocyte injury in vitro and in vivo can be ascribed to its inhibition of the activation and membrane translocation of the pyroptosis executor gasdermin D (GSDMD) in podocytes. DSF also inhibited the increase and activation of the pyroptosis signaling pathway NLRP3-ASC-Caspase-1/IL-18/GSDMD in C3a/C5a-treated podocytes and renal tissue of PHN rats.</p><p><strong>Conclusion: </strong>DSF is a potential drug for MN treatment, and its clinical application needs to be further investigated.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"8 4","pages":"308-318"},"PeriodicalIF":3.7,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/71/90/kdd-0008-0308.PMC9386405.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33482337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Prognostic Nomogram to Predict 30-Day Mortality Risk in Patients with Sepsis-Induced Cardiorenal Syndrome.","authors":"Yiguo Liu,&nbsp;Yingying Zhang,&nbsp;Yuqiu Lu,&nbsp;Hao Tian Li,&nbsp;Chen Yu","doi":"10.1159/000524483","DOIUrl":"https://doi.org/10.1159/000524483","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis-induced cardiorenal syndrome (sepsis-induced CRS) is a devastating medical condition that is frequently associated with a high fatality rate. In this study, we aimed to develop an individualized nomogram that may help clinicians assess 30-day mortality risk in patients diagnosed with sepsis-induced CRS.</p><p><strong>Methods: </strong>A total of 340 patients with sepsis-induced CRS admitted from January 2015 to May 2019 in Shanghai Tongji Hospital were used as a training cohort to develop a nomogram prognostic model. The model was constructed using multivariable logistic analyses and was then externally validated by an independent cohort of 103 patients diagnosed with sepsis-induced CRS from June 2019 to December 2020. The prognostic ability of the nomogram was assessed through discrimination, calibration, and accuracy.</p><p><strong>Results: </strong>Five prognostic factors were determined and included in the nomogram: age, Sequential (sepsis-related) Organ Failure Assessment (SOFA) score, vasopressors, baseline serum creatinine, and the rate of change in myoglobin. Our prognostic nomogram showed well-fitted calibration curves and yielded strong discrimination power with the area under the curve of 0.879 and 0.912 in model development and validation, respectively. In addition, the nomogram prognostic model exhibited an evidently higher predictive accuracy than the SOFA score.</p><p><strong>Conclusions: </strong>We developed a prognostic nomogram model for patients with sepsis-induced CRS and externally validated the model in another independent cohort. The nomogram exhibited greater strength in predicting 30-day mortality risk than the SOFA score, which may help clinicians estimate short-term prognosis and modulate therapeutic strategies.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"8 4","pages":"334-346"},"PeriodicalIF":3.7,"publicationDate":"2022-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/9e/kdd-0008-0334.PMC9386441.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33482338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles That Herald the Scarcity of Oxygen","authors":"Sekyung Oh, Sang-Ho Kwon","doi":"10.1159/000524423","DOIUrl":"https://doi.org/10.1159/000524423","url":null,"abstract":"The natural, membrane-bound nanoscale particles, called extracellular vesicles (EVs) have emerged as an effective, versatile vehicle to transport desired drugs specifically to injury sites. Heralding the presence of the scarcity of oxygen, EVs produced from the cells upregulating the expression of the critical transcriptional regulator of hypoxia, HIF-1, can induce a response in ischemia-reperfusion-damaged cells to ameliorate renal tubular injury and inflammation.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"294 1","pages":"202 - 205"},"PeriodicalIF":3.7,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77549401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}