Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD
Mathias Haarhaus,Mathias Haarhaus,Vincent Brandenburg,Kamyar Kalantar-Zadeh,Kamyar Kalantar-Zadeh,Peter Stenvinkel,Per Magnusson +6 more
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TLDR
Novel mechanisms that link ALP to vascular calcification, inflammation, and endothelial dysfunction in kidney and cardiovascular diseases are reviewed and new drugs that target ALP are discussed, which have the potential to improve cardiovascular outcomes without inhibiting skeletal mineralization.Abstract:
Cardiovascular disease is the main cause of early death in the settings of chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and ageing Cardiovascular events can be caused by an imbalance between promoters and inhibitors of mineralization, which leads to vascular calcification This process is akin to skeletal mineralization, which is carefully regulated and in which isozymes of alkaline phosphatase (ALP) have a crucial role Four genes encode ALP isozymes in humans Intestinal, placental and germ cell ALPs are tissue-specific, whereas the tissue-nonspecific isozyme of ALP (TNALP) is present in several tissues, including bone, liver and kidney TNALP has a pivotal role in bone calcification Experimental overexpression of TNALP in the vasculature is sufficient to induce vascular calcification, cardiac hypertrophy and premature death, mimicking the cardiovascular phenotype often found in CKD and T2DM Intestinal ALP contributes to the gut mucosal defence and intestinal and liver ALPs might contribute to the acute inflammatory response to endogenous or pathogenic stimuli Here we review novel mechanisms that link ALP to vascular calcification, inflammation, and endothelial dysfunction in kidney and cardiovascular diseases We also discuss new drugs that target ALP, which have the potential to improve cardiovascular outcomes without inhibiting skeletal mineralizationread more
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Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases.
José Luis Morgado-Pascual,Sandra Rayego-Mateos,Lucia Tejedor,Beatriz Suarez-Alvarez,MartaMarta Ruiz-ortega +4 more
TL;DR: In this article, the potential of epigenetic therapeutic strategies against bromodomain and extraterminal (BET) proteins for CKD treatment and associated risks is discussed.
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Detection of Bacterial Alkaline Phosphatase Activity by Enzymatic In Situ Self-Assembly of the AIEgen-Peptide Conjugate.
Xue Zhang,Xue Zhang,Chunhua Ren,Fang Hu,Yang Gao,Zhongyan Wang,Huiqiang Li,Jianfeng Liu,Bin Liu,Cuihong Yang +9 more
TL;DR: This study constructed the first fluorescent probe (TPEPy-pY) for sensing bacterial ALP activity and shows excellent selectivity and sensitivity for ALP activity, and envision that more self-assembling fluorescent probes will be designed with higher sensitivity in the near future.
Journal ArticleDOI
Recomendaciones De La Sociedad Espanola De Nefrologia Para El Manejo De Las Alteraciones Del Metabolismo Oseo-Mineral En Los Pacientes Con Enfermedad Renal Cronica. 2021 (SEN-MM)
Jose-Vicente Torregrosa,Jordi Bover Sanjuan,Jorge Cannata Andía,Víctor Lorenzo Sellares,Angel Luis Martín de Francisco Hernández,Isabel Martínez,Juan Mariano Rodríguez Portillo,María Dolores Arenas Jiménez,Emilio González Parra,Francisco Caravaca Magariños,Alejandro Martín Malo,Elvira Fernández Giráldez,Armando Torres Ramírez +12 more
TL;DR: This guideline on the management of patients with diabetes and CKD stage 3b or higher to facilitate informed decision-making by health care professionals with focus on selection of renal replacement therapy, management of glycemic control, and management and prevention of cardiovascular risk is published.
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Recent advances in intestinal alkaline phosphatase, inflammation, and nutrition
TL;DR: Nearly all data confirm the potent anti-inflammatory properties of (I)AP and the negative consequences of its inhibition on health, thus emphasizing nutrition as a potent lever for limiting inflammation.
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Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine.
Yizhi Sun,Janane F. Rahbani,Mark P. Jedrychowski,Christopher L. Riley,Sara Vidoni,Dina Bogoslavski,Bo Hu,Phillip A. Dumesic,Xing Zeng,Alex Wang,Nelson H. Knudsen,Caroline R. Kim,Anthony Marasciullo,José Luis Millán,Edward T. Chouchani,Lawrence Kazak,Bruce M. Spiegelman +16 more
TL;DR: In this paper, the authors provided direct evidence for the molecular basis of this futile creatine cycling activity in mice, which was based on the super-stoichiometric relationship between the amount of creatine added to mitochondria and the quantity of oxygen consumed.
References
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Pharmacokinetic Modeling and Dose Selection in a Randomized, Double-Blind, Placebo-Controlled Trial of a Human Recombinant Alkaline Phosphatase in Healthy Volunteers
Esther Peters,Jules A. A. C. Heuberger,Renger Tiessen,Andrea van Elsas,Rosalinde Masereeuw,Jacques Arend,Jasper Stevens,Peter Pickkers +7 more
TL;DR: A four-compartment model best described the pharmacokinetics of recAP administration, with moderate inter-individual variability on the central volume of distribution and elimination rate constant, and showed that 1-h intravenous infusions of 250, 500 and 1000 U/kg recAP once every 24 h for three consecutive days constituted the dosing regimen that best met the criteria for dose selection in patient studies.
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Circulating and tissue-derived isoforms of bone alkaline phosphatase in Paget's disease of bone.
TL;DR: The bone ALP isoform B2 may be of use in the management of PDB but that has to be further elucidated in subsequent studies.
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Oxidative Stress as Estimated by Gamma-Glutamyl Transferase Levels Amplifies the Alkaline Phosphatase-Dependent Risk for Mortality in ESKD Patients on Dialysis
Claudia Torino,Francesco U.S. Mattace-Raso,Jan L.C.M. van Saase,Maurizio Postorino,Giovanni Tripepi,Francesca Mallamaci,Carmine Zoccali +6 more
TL;DR: GGT amplifies the risk of death associated with high Alk-Phos levels in ESKD patients, compatible with the hypothesis that oxidative stress is a strong modifier of the adverse biological effects of high Al kaline phosphatase levels in this population.
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Alkaline phosphatase is independently associated with renal function in normoalbuminuric type 1 diabetic patients.
TL;DR: In this paper, the authors explored the relationship between markers of NAFLD, namely concentrations of aspartate aminotransferase (AST), alanine aminoton-transfers (ALT), alkaline phosphatase (ALK), γ-glutamyltransferase (GGT), bilirubin, and renal function in type 1 diabetic patients.
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Association of alkaline phosphatase with acute myocardial infarction in a population with high prevalence of hypovitaminosis D.
TL;DR: Increased vitamin-D levels were associated with decreased risk of AMI, while serum glucose, bone-ALP, hypertension and smoking were positively associated with it.