Nephron Clinical Practice最新文献_第7页

Abstracts of the 10th International Podocyte Conference, June 4-6, 2014, Freiburg, Germany. 第十届国际足细胞会议，2014年6月4-6日，德国弗莱堡。

Nephron Clinical Practice Pub Date : 2014-01-01 Epub Date: 2014-05-28 DOI: 10.1159/000363118

引用次数: 1

Maladaptive proximal tubule repair: cell cycle arrest. 近端小管修复不良:细胞周期阻滞。

Nephron Clinical Practice Pub Date : 2014-01-01 Epub Date: 2014-09-24 DOI: 10.1159/000363673

Joseph V Bonventre

{"title":"Maladaptive proximal tubule repair: cell cycle arrest.","authors":"Joseph V Bonventre","doi":"10.1159/000363673","DOIUrl":"https://doi.org/10.1159/000363673","url":null,"abstract":"Acute kidney injury (AKI) leads to worsening of chronic kidney disease (CKD), and CKD predisposes to the clinical entity of AKI. The tubules of the kidney play a central role in the fibrotic response, which ultimately leads to progressive kidney disease. The cellular mechanisms responsible for the epidemiological association between AKI and CKD are complex. In order to unravel characteristics of this direct involvement of the tubules, in particular the proximal tubules, we established a model to specifically target injury to the proximal tubule using a genetic approach to express the simian diphtheria toxin (DT) receptor in the proximal tubule. A single administration of DT to the proximal tubule resulted in inflammation, reversible injury, and adaptive repair. By contrast, thrice repeated injury led to maladaptive repair with sustained tubule injury, vascular rarefaction, proliferation of interstitial myofibroblasts, interstitial fibrosis, and glomerular sclerosis. An important feature of the maladaptive repair process after severe injury is the development of cell cycle arrest in G2/M. There is a subsequent activation of the DNA repair response with activation of a secretory phenotype whereby profibrotic factors are released. This insight introduces a number of potential new targets for therapeutic intervention to prevent and/or arrest CKD progression.","PeriodicalId":19094,"journal":{"name":"Nephron Clinical Practice","volume":"127 1-4","pages":"61-4"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000363673","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32769912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 63

Apoptosis, fibrosis and senescence. 细胞凋亡，纤维化和衰老。

Nephron Clinical Practice Pub Date : 2014-01-01 Epub Date: 2014-09-24 DOI: 10.1159/000363717

Didier Portilla

{"title":"Apoptosis, fibrosis and senescence.","authors":"Didier Portilla","doi":"10.1159/000363717","DOIUrl":"https://doi.org/10.1159/000363717","url":null,"abstract":"Fibrosis is a major hallmark of progressive kidney disease. The cellular mechanisms that lead to kidney tissue fibrosis are complex and include, for example, increased inflammation, increased oxidative stress, and proximal tubule cell death in the form of apoptosis or senescence. Recent studies have identified TWEAK, a tumor necrosis factor-like weak inducer of apoptosis, as a novel cytokine that mediates kidney inflammation in models of renal fibrosis. Inhibition of apoptosis via TWEAK inhibition has been shown to reduce kidney fibrosis. Recent studies using lineage tracing suggest that interstitial pericytes/perivascular fibroblasts differentiate into myofibroblasts and undergo proliferative expansion during fibrosis. Furthermore, increased expression of nuclear peroxisome proliferator-activated receptor-α in proximal tubules can directly reduce increased expression of transforming growth factor-β1 and interstitial inflammation in models of renal fibrosis, which suggests preservation of proximal tubule cell metabolism and integrity represents an important new therapeutic target. In this review, the current evidence and potential molecular mechanisms involved in the development of kidney fibrosis are discussed.","PeriodicalId":19094,"journal":{"name":"Nephron Clinical Practice","volume":"127 1-4","pages":"65-9"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000363717","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32769913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 31

Rationale of mesenchymal stem cell therapy in kidney injury. 间充质干细胞治疗肾损伤的基本原理。

Nephron Clinical Practice Pub Date : 2014-01-01 Epub Date: 2014-09-24 DOI: 10.1159/000363680

Susanne V Fleig, Benjamin D Humphreys

引用次数: 77

Renal functional reserve and renal recovery after acute kidney injury. 急性肾损伤后肾功能储备与肾恢复。

Nephron Clinical Practice Pub Date : 2014-01-01 Epub Date: 2014-09-24 DOI: 10.1159/000363721

Aashish Sharma, Marìa Jimena Mucino, Claudio Ronco

{"title":"Renal functional reserve and renal recovery after acute kidney injury.","authors":"Aashish Sharma, Marìa Jimena Mucino, Claudio Ronco","doi":"10.1159/000363721","DOIUrl":"https://doi.org/10.1159/000363721","url":null,"abstract":"Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use.","PeriodicalId":19094,"journal":{"name":"Nephron Clinical Practice","volume":"127 1-4","pages":"94-100"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000363721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32770355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 194

Intestinal microbiota-kidney cross talk in acute kidney injury and chronic kidney disease. 急性肾损伤和慢性肾病的肠道微生物-肾脏串扰。

Nephron Clinical Practice Pub Date : 2014-01-01 Epub Date: 2014-09-24 DOI: 10.1159/000363209

Sanjeev Noel, Maria N Martina-Lingua, Samatha Bandapalle, Jennifer Pluznick, Abdel Rahim A Hamad, Daniel A Peterson, Hamid Rabb

引用次数: 47

The potential of alkaline phosphatase as a treatment for sepsis-associated acute kidney injury. 碱性磷酸酶治疗败血症相关急性肾损伤的潜力。

Nephron Clinical Practice Pub Date : 2014-01-01 Epub Date: 2014-09-24 DOI: 10.1159/000363256

Esther Peters, Rosalinde Masereeuw, Peter Pickkers

{"title":"The potential of alkaline phosphatase as a treatment for sepsis-associated acute kidney injury.","authors":"Esther Peters, Rosalinde Masereeuw, Peter Pickkers","doi":"10.1159/000363256","DOIUrl":"https://doi.org/10.1159/000363256","url":null,"abstract":"Sepsis-associated acute kidney injury (AKI) is associated with a high attributable mortality and an increased risk of developing chronic kidney failure in survivors. As a successful therapy is, as yet, unavailable, a pharmacological treatment option is clearly warranted. Recently, two small phase II clinical trials demonstrated beneficial renal effects of bovine-derived alkaline phosphatase administration in critically ill patients with sepsis-associated AKI. The rationale behind the renal protective effects remains to be fully elucidated, but is likely to be related to dephosphorylation and thereby detoxification of detrimental molecules involved in the pathogenesis of sepsis-associated AKI. A potent candidate target molecule might be endotoxin (lipopolysaccharide) from the cell wall of Gram-negative bacteria, which is associated with the development of sepsis and becomes nontoxic after being dephosphorylated by alkaline phosphatase. Another target of alkaline phosphatase could be adenosine triphosphate, a proinflammatory mediator released during cellular stress, which can be converted by alkaline phosphatase into the tissue-protective and anti-inflammatory molecule adenosine. Human recombinant alkaline phosphatase, a recently developed replacement for bovine-derived alkaline phosphatase, has shown promising results in the preclinical phase. As its safety and tolerability were recently confirmed in a phase I clinical trial, the renal protective effect of human recombinant alkaline phosphatase in sepsis-associated AKI shall be investigated in a multicenter phase II clinical trial starting at the end of this year.","PeriodicalId":19094,"journal":{"name":"Nephron Clinical Practice","volume":"127 1-4","pages":"144-8"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000363256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32771367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

The spleen: the forgotten organ in acute kidney injury of critical illness. 脾:危重症急性肾损伤中被遗忘的器官。

Nephron Clinical Practice Pub Date : 2014-01-01 Epub Date: 2014-09-24 DOI: 10.1159/000363255

Joseph C Gigliotti, Mark D Okusa

{"title":"The spleen: the forgotten organ in acute kidney injury of critical illness.","authors":"Joseph C Gigliotti, Mark D Okusa","doi":"10.1159/000363255","DOIUrl":"https://doi.org/10.1159/000363255","url":null,"abstract":"Acute kidney injury (AKI) is an increasing medical burden and is independently associated with mortality. AKI is a common comorbidity in the intensive care unit (ICU), with sepsis-associated AKI seen in almost a quarter of all ICU patients. Due to the high mortality seen in these patients, improved therapeutic options are needed. Data from experimental studies in animals support observations in humans that the host immune response to sepsis and trauma contributes to multiorgan failure and the high morbidity and mortality seen in critically ill patients. The spleen, a major component of the reticuloendothelial system, appears to be a key player in the 'cytokine storm' that develops after infection and trauma, and the resultant systemic inflammation is regulated by the autonomic nervous system. Over the past decade, evidence has suggested that controlling the splenic cytokine response improves tissue function and mortality in sepsis and other inflammatory-mediated diseases. One pathway that controls the response of the spleen to sepsis and trauma is the cholinergic anti-inflammatory pathway, and it may provide a key target for therapeutic intervention. Here, we review this concept and highlight the potential use of ultrasound to stimulate the cholinergic anti-inflammatory pathway and reduce systemic inflammation and disease severity.","PeriodicalId":19094,"journal":{"name":"Nephron Clinical Practice","volume":"127 1-4","pages":"153-7"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000363255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32771369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 27

Eculizumab in the treatment of membranoproliferative glomerulonephritis. Eculizumab治疗膜增生性肾小球肾炎。

Nephron Clinical Practice Pub Date : 2014-01-01 Epub Date: 2014-11-11 DOI: 10.1159/000368592

Andrew S Bomback

引用次数: 31

Echocardiography predicts major adverse cardiovascular events after renal transplantation. 超声心动图预测肾移植后主要不良心血管事件。

Nephron Clinical Practice Pub Date : 2014-01-01 Epub Date: 2014-03-07 DOI: 10.1159/000358885

Haotian Gu, Majid Akhtar, Amit Shah, Anjalika Mallick, Marlies Ostermann, John Chambers

{"title":"Echocardiography predicts major adverse cardiovascular events after renal transplantation.","authors":"Haotian Gu, Majid Akhtar, Amit Shah, Anjalika Mallick, Marlies Ostermann, John Chambers","doi":"10.1159/000358885","DOIUrl":"https://doi.org/10.1159/000358885","url":null,"abstract":"Introduction: Cardiovascular disease is a leading cause of morbidity and mortality after renal transplantation. We analysed whether pre-transplant transthoracic echocardiograms (TTE) predicted major adverse cardiovascular events (MACE) after transplant.Methods: We retrospectively analysed clinical and TTE data from patients having renal transplantation at a single centre between 1 January 2000 and 31 December 2010. The TTE were classified as: group A - normal; group B - mild abnormalities expected in renal failure; group C - moderate to severe abnormalities likely to change management. They were also scored based on four independent risk factors [age ≥50, left ventricular (LV) end systolic diameter ≥3.5 cm, LV wall thickness ≥1.4 cm and mitral annulus calcification]. Post-transplantation clinical notes were examined for MACE (death, stroke, myocardial infarction, and surgical or percutaneous revascularisation).Results: There were 343 patients, mean age 47 (range 21-83) years, 210 of whom were male. MACE occurred in 29 (8.5%) at a mean of 3.6 (SD 3.3) years after transplantation. They were older (p ≤ 0.001), had larger LV mass (p = 0.02), LV wall thickness (p = 0.008) and left atrial size (p = 0.001) than those without MACE. The MACE rate for groups A, B and C were 1.8, 13.6 and 16.4% (p ≤ 0.001), respectively. Using the score, the risk of MACE was 4.7, 10.7, 9.2 and 40% for scores 0, 1, 2 and 3 (p = 0.023), respectively.Conclusion: Preoperative transthoracic echocardiography identifies patients at risk of death or non-fatal cardiovascular events even late after renal transplantation. This suggests that echocardiography might be useful to identify patients requiring more aggressive long-term treatment of modifiable vascular risk factors.","PeriodicalId":19094,"journal":{"name":"Nephron Clinical Practice","volume":"126 1","pages":"75-80"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000358885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32186844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8