ArticleBritish journal of pharmacology2015
Alkaline phosphatase protects against renal inflammation through dephosphorylation of lipopolysaccharide and adenosine triphosphate.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 82 citations in OpenAlex.
- A randomized Phase 1b trial evaluating the pharmacodynamics of ilofotase alfa in adults with hypophosphatasia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Trial
- Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL).Intensive care medicine · 2024Trial
- Alkaline Phosphatase Activity and Endotoxemia After Infant Cardiothoracic Surgery.Shock (Augusta, Ga.) · 2019Trial
- Trial
- Pharmacokinetic Modeling and Dose Selection in a Randomized, Double-Blind, Placebo-Controlled Trial of a Human Recombinant Alkaline Phosphatase in Healthy Volunteers.Clinical pharmacokinetics · 2016Trial
- Low Serum Alkaline Phosphatase Levels in Paediatric sepsis Correlate With Acute Kidney Injury: A Multicenter Retrospective Study.Acta paediatrica (Oslo, Norway : 1992) · 2026Article
- A multicenter randomized, double-blinded placebo-controlled phase 2 trial to evaluate safety and efficacy of ilofotase alfa in patients at risk for kidney injury following open heart surgery.Intensive care medicine · 2026Article
- Epigenetics-mediated pathological alterations and their diagnostic and therapeutic potential in sepsis-associated acute kidney injury.Clinical epigenetics · 2026Review
- A study on the association between polycyclic aromatic hydrocarbon (PAH) exposure and kidney function indicators in adolescents: an integrated research combining statistical mediation analysis and network toxicology.International urology and nephrology · 2026Article
- Engineering a T7 bacteriophage to attenuate LPS-driven inflammatory responses during bacteriolysis.Applied and environmental microbiology · 2026Article
- Alkaline Phosphatase Supplementation During Hypothermic and Normothermic Machine Perfusion Improves Metabolic Dysfunction in a Porcine Model of Donor Kidney Preservation.Transplantation direct · 2026Article
- Tissue nonspecific and intestinal alkaline phosphatase crosstalk: a missing link in hypophosphatasia pathophysiology?Journal of translational medicine · 2026Article
- Alkaline Phosphatase as a Potential Biomarker of Muscle Function: A Pilot Study in Patients with Hypophosphatasia.International journal of molecular sciences · 2025Article
- High Neutrophil Alkaline Phosphatase Activity in Adult-Onset Still's Disease.Rheumatology and therapy · 2025Article
- Purinoreceptor P2X7 in Extracellular ATP-Mediated Inflammation through the Spectrum of Kidney Diseases and Kidney Transplantation.Journal of the American Society of Nephrology : JASN · 2025Review
- Targeting CD73 and correcting adenosinergic signaling in critically ill patients.Frontiers in pharmacology · 2025Review
- Alkaline phosphatase treatment of acute kidney injury-an update.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- [Recent developments in acute kidney injury : Definition, biomarkers, subphenotypes, and management].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2024Review
- Tackling sepsis-associated AKI: are there any chances of REVIVAL with new approaches?Intensive care medicine · 2024Article
- Exploration of the Shared Gene Signatures and Molecular Mechanisms between Chronic Bronchitis and Antineutrophil Cytoplasmic Antibody-associated Glomerulonephritis: Evidence from Transcriptome Data.Current pharmaceutical design · 2024Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeRecently, two phase-II trials demonstrated improved renal function in critically ill patients with sepsis-associated acute kidney injury treated with the enzyme alkaline phosphatase. Here, we elucidated the dual active effect on renal protection of alkaline phosphatase. EXPERIMENTAL APPROACH: The effect of human recombinant alkaline phosphatase (recAP) on LPS-induced renal injury was studied in Sprague-Dawley rats. Renal function was assessed by transcutaneous measurement of FITC-sinistrin elimination in freely moving, awake rats. The mechanism of action of recAP was further investigated in vitro using conditionally immortalized human proximal tubular epithelial cells (ciPTEC). KEY
resultsIn vivo, LPS administration significantly prolonged FITC-sinistrin half-life and increased fractional urea excretion, which was prevented by recAP co-administration. Moreover, recAP prevented LPS-induced increase in proximal tubule injury marker, kidney injury molecule-1 expression and excretion. In vitro, LPS-induced production of TNF-α, IL-6 and IL-8 was significantly attenuated by recAP. This effect was linked to dephosphorylation, as enzymatically inactive recAP had no effect on LPS-induced cytokine production. RecAP-mediated protection resulted in increased adenosine levels through dephosphorylation of LPS-induced extracellular ADP and ATP. Also, recAP attenuated LPS-induced increased expression of adenosine A2A receptor. However, the A2A receptor antagonist ZM-241385 did not diminish the effects of recAP. CONCLUSIONS AND IMPLICATIONS: These results indicate that the ability of recAP to reduce renal inflammation may account for the beneficial effect observed in septic acute kidney injury patients, and that dephosphorylation of ATP and LPS are responsible for this protective effect.
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