This study will follow patients admitted to the PICU with sepsis, NICU with sepsis or after abdominal surgery, or CICU who are identified as being at risk for developing acute kidney injury. The investigators will use risk-stratification, biomarker testing, and a functional assessment to predict children and neonates who will become fluid overloaded and develop severe acute kidney injury.

开始日期2024-09-01

申办/合作机构

Children's Hospital & Medical Center

CTR20240684 / Recruiting临床2期

一项旨在评估单次静脉输注TIN816治疗脓毒症相关急性肾损伤（SA-AKI）受试者的安全性和疗效的多中心、随机、双盲、安慰剂对照、四臂、平行组、剂量探索IIb期研究

本研究的目的是在SA-AKI受试者中确定剂量-反应关系，并评价三种不同的TIN816单次给药剂量与安慰剂相比的安全性和疗效。

开始日期2024-08-14

申办/合作机构

诺华中国

[+2]

NCT06517810 / RecruitingN/A

Pediatric Selective Cytopheretic Device (SCD-PED, QUELIMMUNE) for Critically Ill Children With Acute Kidney Injury: A Humanitarian Device Exemption (HDE) Surveillance Registry Protocol

QUELIMMUNE is FDA-approved under an HDE for the treatment of pediatric patients (weight ≥10kg and age ≤22 years) with AKI due to sepsis or a septic condition on antibiotic therapy and requiring RRT.
The purpose of this surveillance registry is to prospectively collect safety data among all patients treated with QUELIMMUNE under the HDE. More specifically, we intend on comparing the incidence of new (secondary) blood stream infections in the first 28 days after SCD-PED initiation to a comparator group of matched CKRT patients with sepsis who did not receive treatment with QUELIMMUNE

开始日期2024-07-01

申办/合作机构

SeaStar Medical, Inc.

100 项与脓毒症所致急性肾损伤相关的临床结果

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100 项与脓毒症所致急性肾损伤相关的转化医学

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0 项与脓毒症所致急性肾损伤相关的专利（医药）

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项与脓毒症所致急性肾损伤相关的文献（医药）

2024-12-31·Renal Failure

Predictive models of sepsis-associated acute kidney injury based on machine learning: a scoping review

Review

作者: Zhu, Manli ; Li, Jie ; Yan, Li

BACKGROUNDWith the development of artificial intelligence, the application of machine learning to develop predictive models for sepsis-associated acute kidney injury has made potential breakthroughs in early identification, grading, diagnosis, and prognosis determination.METHODSHere, we conducted a systematic search of the PubMed, Cochrane Library, Embase (Ovid), Web of Science, and Scopus databases on April 28, 2023, and screened relevant literature. Then, we comprehensively extracted relevant data related to machine learning algorithms, predictors, and predicted objectives. We subsequently performed a critical evaluation of research quality, data aggregation, and analyses.RESULTSWe screened 25 studies on predictive models for sepsis-associated acute kidney injury from a total of originally identified 2898 studies. The most commonly used machine learning algorithm is traditional logistic regression, followed by eXtreme gradient boosting. We categorized these predictive models into early identification models (60%), prognostic prediction models (32%), and subtype identification models (8%) according to their predictive purpose. The five most commonly used predictors were serum creatinine levels, lactate levels, age, blood urea nitrogen concentration, and diabetes mellitus. In addition, a single data source, insufficient assessment of clinical utility, lack of model bias assessment, and hyperparameter adjustment may be the main reasons for the low quality of the current research.CONCLUSIONSHowever, studies on the nondeath prognostic outcomes, the long-term clinical outcomes, and the subtype identification models are insufficient. Additionally, the poor quality of the research and the insufficient practicality of the model are problems that need to be addressed urgently.

2024-12-31·Renal Failure

Clinical value of soluble urokinase-type plasminogen activator receptor in predicting sepsis-associated acute kidney injury

Article

作者: Shao, Fengmin ; Gu, Yue ; Li, Han ; Jiao, Xiaojing ; Wang, Juntao ; Zhang, Wenwen ; Zhao, Xiaoru ; Deng, Xiaoyu ; Yan, Lei ; Zhou, Jing

BACKGROUNDSepsis-associated acute kidney injury (S-AKI) is a critical illness and is often associated with high morbidity and mortality rates. The soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator and is involved in kidney injury. However, its diagnostic value in S-AKI patients remains unclear. Therefore, we assessed the early predictive value of suPAR for S-AKI patients.METHODSWe prospectively enrolled adult patients, immediately after fulfilling the sepsis-3 criteria. Plasma suPAR levels at 0-, 12-, 24-, and 48-h post-sepsis diagnosis were measured. S-AKI development was the primary outcome. S-AKI risk factors were analyzed using logistic regression, and the value of plasma suPAR for early S-AKI diagnosis was assessed using receiver operating characteristic (ROC) curves.RESULTSOf 179 sepsis patients, 63 (35.2%) developed AKI during hospitalization. At 12-, 24-, and 48-h post-sepsis diagnosis, plasma suPAR levels were significantly higher in patients with S-AKI than in patients without S-AKI (p < 0.05). The plasma suPAR had the highest area under the ROC curve of 0.700 (95% confidence interval (CI), 0.621-0.779) at 24-h post-sepsis diagnosis, at which the best discrimination ability for S-AKI was achieved with suPAR of ≥6.31 ng/mL (sensitivity 61.9% and specificity 71.6%). Logistic regression analysis showed that suPAR at 24-h post-sepsis diagnosis remained an independent S-AKI risk factor after adjusting for mechanical ventilation, blood urea nitrogen, and pH.CONCLUSIONSThe findings suggest that plasma suPAR may be a potential biomarker for early S-AKI diagnosis.

2024-12-31·Renal Failure

Usp9x contributes to the development of sepsis-induced acute kidney injury by promoting inflammation and apoptosis in renal tubular epithelial cells via activation of the TLR4/nf-κb pathway

Article

作者: Ouyang, Yingdong ; Cao, Chunshui ; Lei, Yingchao ; Huang, Shipeng ; Gong, Shuhao ; Xiong, Huawei ; Wang, Ying

As a pattern recognition receptor, Toll-like receptor 4 (TLR4) is crucial for the development and progression of acute kidney injury (AKI). This study aims to explore whether the deubiquitinase Usp9x influences the TLR4/NF-B pathway to cause sepsis-induced acute kidney injury (S-AKI). The model of AKI was established in Sprague-Dawley rats using the cecal ligation and puncture (CLP) method, while renal tubular epithelial cell NRK-52E was stimulated with lipopolysaccharide (LPS) in vitro. All plasmids were transfected into NRK-52E cells according to the indicated group. The deubiquitinase of TLR4 was predicted by the online prediction software Ubibrowser. Subsequently, Western blot and Pearson correlation analysis identified Usp9x protein as a potential candidate. Co-IP analysis verified the interaction between TLR4 and Usp9x. Further research revealed that overexpression of Usp9x inhibited degradation of TLR4 protein by downregulating its ubiquitination modification levels. Both in vivo and in vitro experiments observed that interference with Usp9x effectively alleviated the inflammatory response and apoptosis of renal tubular epithelial cells (RTECs) induced by CLP or LPS, whereas overexpression of TLR4 reversed this situation. Transfection with sh-Usp9x in NRK-52E cells suppressed the expression of proteins associated with the TLR4/NF-κB pathway induced by LPS. Moreover, the overexpression of TLR4 reversed the effect of sh-Usp9x transfection. Therefore, the deubiquitinase Usp9x interacts with TLR4, leading to the upregulation of its expression through deubiquitination modification, and the activation of the TLR4/NF-κB signaling pathway, thereby promoting inflammation and apoptosis in renal tubular epithelial cells and contributing to sepsis-induced acute kidney injury.

项与脓毒症所致急性肾损伤相关的新闻（医药）

2024-02-05

·GlobeNewswire-Health Care

Memo Therapeutics AG Strengthens Management Team

PRESS RELEASE Memo Therapeutics AG Strengthens Management Team Appoints Kristie B. Clemmer as VP Clinical Operations and Dr. Maartje Verschuur as VP CMC and Supply Chain Management Schlieren / Zurich, Switzerland, February 5, 2024 – Memo Therapeutics AG (or “MTx”), a late-stage biotech company developing best-in-class therapeutic antibodies for viral infections and oncology, announced today that it has strengthened its senior team with the appointments of Kristie B. Clemmer and Dr. Maartje Verschuur as VP Clinical Operations and VP CMC and Supply Chain Management, respectively, effective today. Ms. Clemmer is an accomplished global clinical research leader with over 20 years of experience directing international clinical operations. She most recently served as VP, Clinical Operations at AM-Pharma where she led teams across North America, Europe, and Japan for a Phase III critical care trial in sepsis-associated acute kidney injury. Ms. Clemmer previously held senior leadership positions at the Contract Research Organizations PRA Health Sciences and PPD. Prior to her career in clinical research, Ms. Clemmer was an intensive care unit/emergency room nurse. She holds a BSc degree in Nursing with a Minor in Biology from Barton College, US. Dr. Verschuur has more than 19 years of experience in biologics drug development and manufacturing, with a focus on Chemistry Manufacturing and Controls (CMC). She has broad knowledge in the late-stage development and commercialization of biologics, and was a key contributor to five product candidates that have successfully gained market approvals. She joins MTx from AM-Pharma, where she was responsible for all drug substance activities including Phase III clinical manufacturing. Dr. Verschuur previously held a variety of senior CMC roles including at Venn Life Sciences BV, Batavia Biosciences BV and AbbVie Inc. Dr. Verschuur completed her PhD in Molecular/Cell Biology from Leiden University, The Netherlands and has an MSc in Biotechnology from Wageningen University, The Netherlands. Eric van den Berg, CEO of MTx, commented: “It is a pleasure to welcome Kristie and Maartje to MTx. They bring a wealth of experience successfully directing global clinical operations and biologics drug development and manufacturing. Their insights and expertise will be instrumental as we progress our Phase II trial and prepare for Phase III of our lead program, AntiBKV, and develop our promising pipeline of best-in-class therapeutic antibodies.” -Ends- About Memo Therapeutics AGMemo Therapeutics AG (“MTx”) is a late-stage biotech company developing best-in-class therapeutic antibodies to transform the lives of patients with viral infections and cancer. MTx’s lead program, AntiBKV, is a highly effective and safe neutralizing antibody to treat BK virus infection in kidney transplant recipients. This infection can lead to nephropathy, loss of kidney function, as well as organ failure and rejection. MTx’s pipeline consists of additional candidate therapeutic antibodies focusing on infectious diseases, such as cytomegalovirus (“CMV”), immuno-oncology targets as well as a partnership with Ono Pharmaceutical. MTx is a private company located in Schlieren / Zurich, Switzerland. Contacts Memo Therapeutics AG info@memo-therapeutics.com ICR ConsiliumAmber Fennell, Ashley Tappmemotx@consilium-comms.com+44 (0)20 3709 5700

高管变更临床3期

2023-09-26

·FierceBiotech

AM-Pharma cuts staff, says goodbye to CEO as lead kidney injury asset redirected

AM-Pharma boasts some major Big Pharma investors, including Pfizer, Takeda and AbbVie. After failing in a phase 3 study for a severe kidney complication of sepsis, AM-Pharma is redirecting its lead program to a different kind of kidney damage. Along with the revised clinical development strategy, the Dutch biotech is cutting staff and getting a new CEO. A phase 3 trial for ilofotase alfa in sepsis-associated acute kidney injury (SA-AKI) was halted for futility in October 2022 after failing to improve the rate of all-cause deaths at 28 days. SA-AKI is a complex and severe complication of sepsis when the body’s infection-fighting mechanism turns on itself. The condition has a high rate of death and is associated with poor outcomes. Despite failing the study, AM-Pharma noted a reduction in major adverse kidney events by day 90, with an investigator saying “the renal benefit observed in this study in ilofotase alfa-treated patients cannot be ignored.” This potential benefit was revealed in a pre-specified secondary analysis of all 649 patients. AM-Pharma has decided to heed the warning, but it’s going to take some growing pains to get there. The company announced Tuesday an unspecified workforce reduction but declined in an email to specify the number of people affected. The company’s LinkedIn page lists 33 employees. Long-time CEO Erik van den Berg will also pass the reins to Juliane Bernholz, Ph.D., who had been serving as chief operating officer. Van den Berg had held the top role since 2011 and will now join the company’s supervisory board and remain a strategic advisor. Ilofotase alfa will proceed in two indications, with cardiac surgery-associated renal damage serving as the lead indication. A phase 2 study will test the therapy in 150 patients who are at risk of developing renal damage based on pre-operative kidney function and scheduled for a complex open-heart surgery. A separate phase 1b study is already underway to use ilofotase alfa as an enzyme replacement therapy for patients with the rare bone metabolism disorder hypophosphatasia. Initial clinical results are expected before the end of the year. AM-Pharma boasts some major Big Pharma investors, including Pfizer, Takeda and AbbVie. Others include Nestle, Cowen Healthcare Investments and Forbion. Pfizer put down $87.5 million in 2015 to take a minority interest in the Utrecht, Netherlands-based company but also snagged an option to buy it outright for $512.5 million if interested once phase 2 results for ilofotase alfa were ready. The New York Big Pharma walked away after getting a look at the data in 2018. The revised clinical development plan is supported by existing investors who have supplied additional funding, although AM-Pharma did not provide details.

临床2期并购临床3期高管变更

2023-04-04

·BioSpace

ADQI Group Recognizes PenKid as Relevant Functional Biomarker for Sepsis-Associated Acute Kidney Injury

The Acute Disease Quality Initiative (ADQI) has published a consensus statement that strongly recommends using innovative biomarkers to improve the management of sepsis-associated acute kidney injury (SA-AKI). According to the statement, the kidney function biomarker Proenkephalin A 119-159 (penKid) can detect subclinical AKI, enabling early risk prediction for upcoming AKI. Looking ahead, integrating clinical information including relevant biomarkers might support the identification of specific disease endotypes and organ-related tolerance mechanisms as a basis for future personalized therapies. HENNIGSDORF and BERLIN, GERMANY / ACCESSWIRE / April 4, 2023 / Diagnostic company SphingoTec announces that in the consensus statement of the 28 th ADQI workgroup, penKid is recognized as a relevant functional biomarker able to predict SA-AKI with high accuracy (1). Sepsis is a life-threatening disease that leads to organ dysfunction, accounting for up to 70% of all cases of AKI in critically ill patients (1). The current standard of care diagnostics for AKI has considerable limitations, therefore it is an urgent need to implement new biomarkers to enable better patient management. According to the consensus statement, penKid can identify patients with sepsis who are at an increased risk of developing AKI and major adverse kidney events (1). The study cites previous research that demonstrates the ability of penKid to detect subclinical AKI, including multicentric studies that shows the incidence and outcome relevance of subclinical AKI in critically ill patients (2,3). SA-AKI is a heterogeneous syndrome, with multiple mechanisms that contribute to its development. The recommendations also include the use of biomarkers and clinical information to identify distinct disease mechanisms and characteristics that can inform personalized treatment decisions in clinical practice. Furthermore, the same granular approach focused on early patient risk identification could also enable predictive enrichment in randomized trials of development-stage therapeutics. Dr. Florian Uhle, Medical Director at SphingoTec commented "There are few options available for assessing the kidney function in the context of AKI, and the standard of care biomarkers have well-known limitations, especially in septic patients. PenKid offers additional insights that could help clinicians recognize subclinical AKI and take preventive measures before the true problem even occurs. Since the main therapy in AKI relies on the management of symptoms, there is also a high need to advance the drug development and use these tools to support the identification of the right patients with the highest benefit and no harm in clinical trials." Beyond the early detection of SA-AKI, previous scientific evidence shows that penKid has other applications that make it a versatile biomarker for kidney function assessment. PenKid correlates to the true glomerular filtration rate (true GFR), detects the presence and severity of AKI, identifies patients at high risk of unfavorable outcomes, and indicates renal recovery, even under dialysis (3,4). ### References: Zarbock, A. et al. Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup. Nat Rev Nephrol (2023). Depret, F. et al. Incidence and outcome of subclinical acute kidney injury using penKid in critically ill patients. Am. J. Respir. Crit. Care Med. 202, 822-829 (2020). Hollinger, A. et al. Proenkephalin A 119-159 (Penkid) is an early biomarker of septic acute kidney injury: the kidney in sepsis and septic shock (Kid-SSS) study. Kidney Int. Rep. 3, 1424-1433 (2018). von Groote T et al. Proenkephalin A 119-159 predicts early and successful liberation from renal replacement therapy in critically ill patients with acute kidney injury: a post hoc analysis of the ELAIN trial. Crit Care 26, 333 (2022). About SphingoTec SphingoTec GmbH ("SphingoTec"; Hennigsdorf near Berlin, Germany) is a commercial-stage diagnostic company focusing on innovative critical care biomarkers for the diagnosis, prediction, and monitoring of acute medical conditions. SphingoTec's innovative markers are made available on different IVD platforms. SphingoTec's proprietary biomarker portfolio includes Proenkephalin A 119-159 (penKid), a biomarker for the assessment of kidney function in critical diseases, and bioactive Adrenomedullin 1-52 (bio-ADM), a biomarker for the assessment of endothelial function in conditions like sepsis. Media contact: Ruxandra Lenz Head of Marketing and Communication SphingoTec GmbH Neuendorfstr. 15 A 16761 Hennigsdorf Tel. +49-3302-20565-0 SOURCE: SphingoTec GmbH View source version on accesswire.com: