Currently there are no pharmacological therapies licensed to treat sepsis-associated acute kidney injury (AKI). Considering the high incidence and mortality of sepsis-associated AKI, there is an urgent medical need to develop effective pharmacological interventions. Two phase II clinical trials recently demonstrated beneficial effects of the enzyme alkaline phosphatase (AP). In critically ill patients with sepsis-associated AKI, treatment with AP reduced the urinary excretion of tubular injury biomarkers and plasma markers of inflammation, which was associated with improvement of renal function. The dephosphorylating enzyme, AP, is endogenously present in the renal proximal tubule apical membrane but becomes depleted during ischemia-induced AKI, thereby possibly contributing to further renal damage. The exact mechanism of action of AP in AKI is unknown, but might be related to detoxification of circulating lipopolysaccharide and other proinflammatory mediators that lose their proinflammatory effects after dephosphorylation. Alternatively, tissue damage associated with systemic inflammation might be attenuated by an AP-mediated effect on adenosine metabolism. Adenosine is a signaling molecule that has been shown to protect the body from inflammation-induced tissue injury, which is derived through dephosphorylation of ATP. In this Perspectives article, we discuss the clinical activity of AP and its putative molecular modes of action, and we speculate on its use to treat and possibly prevent sepsis-associated AKI.
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http://dx.doi.org/10.1124/jpet.112.198226 | DOI Listing |
J Ethnopharmacol
January 2025
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, People's Republic of China. Electronic address:
Ethnopharmacological Relevance: The whole plant of Laggera alata is frequently utilize to remedy inflammatory diseases including nephritis as a traditional Chinese medicine. However, its active ingredients and mechanism of action against sepsis-associated acute kidney injury (SA-AKI) are unknown.
Aim Of The Study: This study aimed to identify active compounds from L.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
August 2024
Department of Emergency, Xiangya Hospital, Central South University, Changsha 410008, China.
Pyroptosis is a form of programmed cell death triggered by inflammatory caspases, dependent on the gasdermin (GSDM) family proteins forming membrane pores in the plasma membrane, with GSDM proteins serving as the executors of pyroptosis. This process can activate a robust inflammatory response through a cascade effect. Sepsis-associated acute kidney injury (SA-AKI) is a classical inflammatory disease with no specific therapeutic drug available.
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December 2025
Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.
Objective: To investigate the association between renal mean perfusion pressure (MPP) and prognosis in sepsis-associated acute kidney injury (SA-AKI).
Methods: Data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Group-based trajectory modeling (GBTM) was applied to identify dynamic MPP patterns, while restricted cubic spline (RCS) curves were utilized to confirm the non-linear relationship between MPP and mortality.
Diagnostics (Basel)
December 2024
First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece.
Sepsis-associated acute kidney injury (SA-AKI) is defined as the development of AKI in the context of a potentially life-threatening organ dysfunction attributed to an abnormal immune response to infection. SA-AKI has been associated with increased mortality when compared to sepsis or AKI alone. Therefore, its early recognition is of the utmost importance in terms of its morbidity and mortality rates.
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December 2024
Department of Nephrology, Tangdu Hospital, The Fourth Military Medical University, Air Force Medical University, Xi'an, Shaanxi Province, China.
Background: Plasma oxidized lipids are intimately linked to immune regulation as bioactive mediators. However, it is not clear whether they are related to the progression of sepsis-associated acute kidney injury (SA-AKI) and the effect of continuous renal replacement therapy (CRRT). This study intends to explore the changes in certain oxidized lipid during CRRT treatment and their correlation with the immune microenvironment and prognosis by analyzing plasma oxidative lipidomics.
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