Nephron最新文献

{"title":"Diosgenin improves lipid metabolism in diabetic nephropathy via regulation of miR-148b-3p/DNMT1/FOXO1 axis.","authors":"Min Luo, Zongren Hu, Jichang Yang, Jinhan Yang, Wen Sheng, Chengxiong Lin, Dian Li, Qinghu He","doi":"10.1159/000541690","DOIUrl":"https://doi.org/10.1159/000541690","url":null,"abstract":"<p><strong>Background: </strong>The progression of diabetic nephropathy (DN) is closely associated with lipid accumulation. Diosgenin (Dio) plays a beneficial role in the lipid metabolism associated with multiple diseases. Thus, the mechanism underlying Dio's function in DN associated with aberrant lipid accumulation warrants further investigation.</p><p><strong>Methods: </strong>To model DN in vitro, HK-2 cells were treated with high glucose (HG) and palmitic acid. Cell viability was evaluated using MTT assay. The triglyceride (TG) content in HK-2 cells was measured using a commercial assay kit. The formation of lipid droplets in HK-2 cells was observed using Oil Red O staining. The expression levels of mRNA and protein were detected using RT-qPCR and western blot, respectively. The DNA methylation of FOXO1 was assessed using MSP. The interaction between DNMT1 and the FOXO1 promoter was confirmed by ChIP assay.</p><p><strong>Results: </strong>Dio treatment reduced TG levels and lipid droplet formation in HK-2 cells co-treated with HG and palmitic acid. Simultaneously, the levels of miR-148b-3p and FOXO1 were increased by Dio, while Dio decreased the expression levels of DNMT1 and SREBP-2. Meanwhile, miR-148b-3p can bind to DNMT1, which in turn inhibits the expression of FOXO1 by mediating the DNA methylation of FOXO1. In addition, FOXO1 negatively regulates the expression of SREBP-2 by interacting with the SREBP-2 promoter. MiR-148b-3p inhibition or silencing of FOXO1 abolished the inhibitory effect of Dio on TG production and lipid droplet formation. This effect was further exacerbated by the downregulation of DNMT1. FOXO1 overexpression may counteract the promotive effects of miR-148b-3p inhibitor on lipid accumulation.</p><p><strong>Conclusion: </strong>Dio treatment reduced TG production and lipid droplet formation in HK-2 cells during the progression of DN by modulating the miR-148b-3p/DNMT1/FOXO1/SREBP-2 axis. This finding provides new evidence supporting the therapeutic potential of Dio for DN.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-23"},"PeriodicalIF":2.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739985","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}

{"title":"Urine miR-340-5p predicts the adverse prognosis of sepsis-associated acute kidney injury and regulates renal tubular epithelial cell injury by targeting KDM4C.","authors":"Mengmeng Pu, Huanhuan Zhao, Silei Xu, Xiaohui Gu, Qiang Feng, Peng Huang","doi":"10.1159/000541348","DOIUrl":"https://doi.org/10.1159/000541348","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis-associated acute kidney injury (SA-AKI) is a common complication of sepsis. miR-340-5p has been identified as an effective biomarker of various human diseases. As the downstream target, the involvement of Lysine (K)-specific demethylase 4C (KDM4C) in SA-AKI would help interpret the regulatory mechanism of miR-340-5p. The significance of miR-340-5p in the onset and progression of SA-AKI was evaluated to provide a potential therapeutic target for SA-AKI.</p><p><strong>Methods: </strong>This study enrolled 64 healthy individuals (control) and 159 sepsis patients (92 SA-AKI and 67 non-AKI) and collected urine samples. The urine level of miR-340-5p was analyzed by PCR, and a series of statistical analyses were conducted to assess the clinical significance of miR-340-5p in the occurrence and development of SA-AKI. The injured renal tubular epithelial cells were established with LPS induction. The roles of miR-340-5p in cellular processes were evaluated.</p><p><strong>Results: </strong>Increasing urine miR-340-5p discriminated SA-AKI patients from healthy individuals (AUC = 0.934) and non-AKI sepsis patients (AUC = 0.806) sensitively. Additionally, elevated miR-340-5p could predict the adverse prognosis (HR = 5.128, 95% CI = 1.259-20.892) and malignant development of SA-AKI patients. In vitro, lipopolysaccharide (LPS) also induced an increased level of miR-340-5p and significant cell injury in the renal tubular epithelial cell, silencing miR-340-5p could alleviate the suppressed proliferation, migration, and invasion caused by LPS. In mechanism, miR-340-5p negatively regulated KDM4C, which mediated the function of miR-340-5p.</p><p><strong>Conclusion: </strong>miR-340-5p served as a diagnostic and prognostic biomarker of SA-AKI and regulated renal tubular epithelial cell injury via modulating KDM4C.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-20"},"PeriodicalIF":2.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648456","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}

{"title":"Exploring the Critical Role of Tight Junction Proteins in Kidney Disease Pathogenesis.","authors":"David Jayne, Corentin Herbert, Vincent Anquetil, Geoffrey Teixeira","doi":"10.1159/000542498","DOIUrl":"https://doi.org/10.1159/000542498","url":null,"abstract":"<p><strong>Background: </strong>Kidney disease poses a significant global health challenge, marked by a rapid decline in renal function due to a variety of causative factors. A crucial element in the pathophysiology of kidney disease is the dysregulation of epithelial cells, which are vital components of renal tissue architecture. The integrity and functionality of these cells are largely dependent on tight junctions (TJ) proteins, complex molecular structures that link adjacent epithelial cells. These TJ not only confer cellular polarity and maintain essential barrier functions but also regulate epithelial permeability.</p><p><strong>Summary: </strong>TJ proteins are pivotal in their traditional role at cell junctions and in their non-junctional capacities. Recent research has shifted the perception of these proteins from mere structural elements to dynamic mediators of kidney disease, playing significant roles in various renal pathologies. This review explores the multifaceted roles of TJ proteins, focusing on their functions both within and external to the renal epithelial junctions. It highlights how these proteins contribute to mechanisms underlying kidney disease, emphasizing their impact on disease progression and outcomes.</p><p><strong>Key messages: </strong>TJ proteins have emerged as significant players in the field of nephrology, not only for their structural role but also for their regulatory functions in disease pathology. Their dual roles in maintaining epithelial integrity and mediating pathological processes make them promising therapeutic targets for kidney disease. Understanding the intricate contributions of TJ proteins in kidney pathology offers potential for novel therapeutic strategies, aiming to modulate these proteins to halt or reverse the progression of kidney disease.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-42"},"PeriodicalIF":2.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624128","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}

{"title":"Association of Serum Ferritin Levels with Short-Term Mortality Risk in Sepsis-associated Acute Kidney Injury: A Retrospective Cohort Study.","authors":"Jie Sun, Ying Qi, Yan Wang, Wenxin Wang, Pengpeng Meng, Changjin Han, Bing Chen","doi":"10.1159/000542410","DOIUrl":"https://doi.org/10.1159/000542410","url":null,"abstract":"<p><p>Abstract： Background: This study aimed to assess the prognostic significance of serum ferritin levels in sepsis-associated acute kidney injury (SA-AKI) and their correlation with short-term mortality. Despite the established predictive value of serum ferritin in various serious diseases, its specific prognostic relevance in SA-AKI remains unexplored. Therefore, this study aimed to fill this research gap by investigating the association between serum ferritin levels and short-term mortality in patients diagnosed with SA-AKI.</p><p><strong>Methods: </strong>This retrospective cohort study used clinical information from the Medical Information Mart for Intensive Care-IV(MIMIC-IV) database to include all patients with SA-AKI admitted to the Intensive Care Unit(ICU) for the first time. The relationship between serum ferritin levels and 28-day mortality was explored using restricted cubic splines. Kaplan Meier curves and Cox regression models were utilized to evaluate the association between serum ferritin levels and mortality. Subgroup analysis is used to verify the stability of previous results.</p><p><strong>Results: </strong>In this study, a total of 878 patients (486 males and 392 females) with a median age of 63.7 years were enrolled. The results showed that increasing serum ferritin levels were linearly associated with a gradual increase in 28-day mortality rates. Specifically, the highest quartile group had a significantly higher 28-day mortality compared to the reference group (the first ferritin quartile). After adjusting for various factors, the fully adjusted hazard ratios (HRs) were calculated to be 1.92 (95% CI: 1.25~2.97, p=0.003).</p><p><strong>Conclusion: </strong>In patients with SA-AKI, higher serum ferritin levels are associated with an increased 28-day mortality rate.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-16"},"PeriodicalIF":2.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624121","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}

{"title":"Renal endowment in men and women: start from the beginning.","authors":"Barbara Imberti, Ariela Benigni","doi":"10.1159/000542411","DOIUrl":"https://doi.org/10.1159/000542411","url":null,"abstract":"<p><p>The development of the human kidney leads to the establishment of nephron endowment through a process influenced by both genetic and environmental factors. There is individual variability regarding nephron endowment and factors including aging and pathological conditions contribute to the decline in the number of nephrons, impacting renal function. Genetic determinants, such as mutations in crucial developmental genes like Pax2, and epigenetic mechanisms mediated by key enzymes including sirtuin 3, play critical roles in the regulation of the number of nephrons, with implications for kidney disease susceptibility. Sexual dimorphism significantly influences kidney development and function, with the number of nephrons being significantly lower in females, consistent with lower female birth weight, which is considered a surrogate for nephron endowment. Also, although females have fewer nephrons, they experience a slower decline in GFR compared to males. Gender disparity in chronic kidney disease progression has been attributed to factors such as metabolism, oxidative stress, renal hemodynamics, and sex hormones. Understanding the complexities of nephron endowment variability, genetic determinants, and sexual dimorphism in kidney development and function is crucial for elucidating the mechanisms underlying individual kidney disease susceptibility and progression. Further research in this field holds promise for the development of personalized approaches to kidney disease prevention, management, and treatment.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604612","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}

{"title":"A case of IgG4-related disease manifesting as extensive abdominal periarteritis and membranous nephropathy, successfully controlled with low-dose steroid therapy without relapse or complications.","authors":"Minami Matsumoto, Shinya Yamamoto, Hideki Yokoi, Sho Koyasu, Shigeo Hara, Takahiro Tsuji, Minamiguchi Sachiko, Motoko Yanagita","doi":"10.1159/000542414","DOIUrl":"https://doi.org/10.1159/000542414","url":null,"abstract":"<p><p>IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disease that can affect nearly every organ system, including blood vessels and the kidney. IgG4-related vascular lesions mainly involve the aorta, and the dominant renal manifestation is tubulointerstitial nephritis (TIN). Here, we report a case of IgG4-RD demonstrating extensive abdominal periarteritis and membranous nephropathy (MN). The patient was a 71-year-old man with peptic ulcer who developed nephrotic syndrome, with a low serum albumin level (1.8 g/dL), massive urinary protein (6.1 g/day), and high serum IgG4 level (435 mg/dL). Computed tomography images revealed soft tissue mass around the medium-sized abdominal arteries. Renal pathological findings showed MN and focal infiltration of numerous IgG4-positive cells in the interstitium. The findings of high serum IgG4 levels, periarteritis, and focal inflammation with rich IgG4-positive plasma cells led to the diagnosis of IgG4-RD. We chose low-dose steroid therapy to prevent the recurrence of the peptic ulcer and aneurysm formation in the affected arteries, which can occur with medium to high doses of prednisolone. We successfully controlled IgG4-related periarteritis and kidney disease without relapse or complications. The varied clinical manifestations of IgG4-RD sometimes make the diagnosis challenging. However, clinicians should diagnose IgG4-RD based on serological, radiological, and pathological evaluations because, without appropriate therapy, IgG4-RD can lead to irreversible organ failure caused by swelling, obstruction, or fibrosis of the organs.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-17"},"PeriodicalIF":2.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576460","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}

{"title":"Advances in molecular imaging of kidney diseases.","authors":"Barbara Mara Klinkhammer, Ilknur Ay, Peter Caravan, Anna Caroli, Peter Boor","doi":"10.1159/000542412","DOIUrl":"https://doi.org/10.1159/000542412","url":null,"abstract":"<p><p>Background Diagnosing and monitoring kidney diseases traditionally rely on blood and urine analyses and invasive procedures such as kidney biopsies, the latter offering limited possibilities for longitudinal monitoring and a comprehensive understanding of disease dynamics. Current non-invasive methods lack specificity in capturing intrarenal molecular processes, hindering patient stratification and patient monitoring in clinical practice and clinical trials. Summary Molecular imaging enables non-invasive and quantitative assessment of physiological and pathological molecular processes. By using specific molecular probes and imaging technologies, e.g., magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), or ultrasound (US), molecular imaging allows the detection and longitudinal monitoring of disease activity with spatial and temporal resolution of different kidney diseases and disease-specific pathways. Several approaches have already shown promising results in kidneys and exploratory clinical studies, and validation is needed before implementation in clinical practice. Key messages Molecular imaging offers a non-invasive assessment of intrarenal molecular processes, overcoming the limitations of current diagnostic methods. It has the potential to serve as companion diagnostics, not only in clinical trials, aiding in patient stratification and treatment response assessment. By guiding therapeutic interventions, molecular imaging might contribute to the development of targeted therapies for kidney diseases.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-19"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576465","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}

{"title":"Characteristics of successful PTRA cases with severely impaired kidney function caused by bilateral atherosclerotic stenosis: A case series.","authors":"Hisashi Sugimoto, Shinya Yamamoto, Motoko Yanagita","doi":"10.1159/000542416","DOIUrl":"https://doi.org/10.1159/000542416","url":null,"abstract":"<p><p>Previous randomized controlled trials have not demonstrated the benefits of renal artery stenting with respect to kidney function. However, these trials did not focus on patients with severely impaired kidney function caused by severe bilateral stenosis. Therefore, the efficacy of stenting in such patients remains unclear. We report four cases of successful PTRA with severely impaired kidney function with rapid decline caused by bilateral atherosclerotic stenosis. The catheterization before irreversible parenchymal damages was useful in improving kidney function dramatically in these cases of severe bilateral renal artery stenosis. Furthermore, we examined the clinical characteristics of the four cases to identify the potential predictors of PTRA effectiveness. Notably, bilateral renal artery >90% stenosis, elevated plasma renin activity, eGFR <15 mL/min/1.73 m2 with an accelerated decline within 6 months before PTRA (> 50 mL/min/1.73 m2/6 months), and resistance index (RI) <0.7 were identified as common findings. PTRA should be considered a treatment strategy for patients with these features to preserve kidney function and avoid dialysis therapy.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-12"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576472","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}

{"title":"Sex Differences in Kidney Health and Disease.","authors":"Brian J Harvey, Diego Alvarez de la Rosa","doi":"10.1159/000541352","DOIUrl":"https://doi.org/10.1159/000541352","url":null,"abstract":"<p><strong>Background: </strong>Sex differences exist in kidney physiology and disease which are underpinned by the biological actions of the sex hormones estrogen, progesterone and testosterone. In this review, we present an up-to-date discussion of the hormonal and molecular signalling pathways implicated in sex differences in kidney health and disease.</p><p><strong>Summary: </strong>Estrogen and progesterone have protective effects on renal blood flow, glomerular filtration rate and nephron ion and water reabsorptive processes, whereas testosterone tends to compromise these functions. The biological effects of estrogen appear to be the most important in reinforcing kidney function and protecting against kidney diseases in females. The actions of estrogen are myriad but all tend to bolster kidney physiology to maintain a steady-state and adaptable extracellular fluid volume (ECFV) and blood pressure. Estrogen safeguards ECFV homeostasis by stimulating renal epithelial sodium channel (ENaC) and water channel (AQP2) expression and transport function. Renal maintenance of ECFV within narrow physiological limits is a first-line of defense against hypertension and lowers the risk of cardiovascular disease in women. The estrogenic and XX chromosome basis for a female advantage are evident in a wide range of kidney diseases including acute kidney injury, chronic kidney disease, end-stage kidney disease, diabetic kidney disease, and polycystic kidney disease. The molecular mechanisms involve estrogen regulation of nephron ion and water transport, genetic immunogenic responses, activation of the protective arm of the renin angiotensin-aldosterone system and XX chromosome reinforcement of immune responses. Kidney disease can also predispose patients to cancer and women are protected in renal cancer with lower incidence, morbidity, and mortality than age-matched men with the disease.</p><p><strong>Key messages: </strong>This review underscores the importance of incorporating sex-specific considerations into clinical practice and basic research to bridge the gap in understanding and addressing biological sex disparities in kidney disease and renal cancer.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-27"},"PeriodicalIF":2.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470479","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}

{"title":"Myths, Realities, and Pathways Forward: A Patient's Thoughts on Person-Centred Care.","authors":"Bill Wang","doi":"10.1159/000541730","DOIUrl":"10.1159/000541730","url":null,"abstract":"","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-7"},"PeriodicalIF":2.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470478","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}