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Phosphate salt selection affects mortality and vascular calcification in the adenine-induced chronic kidney disease mouse model.

作者信息

Dargam Valentina, Ashbrook Sophie K, da Silva Nogueira Perony, Bakhshian Nik Amirala, Hutcheson Joshua D

机构信息

Department of Biomedical Engineering, Florida International University, Miami, Florida, United States.

Department of Biological Sciences, Florida International University, Miami, Florida, United States.

出版信息

Am J Physiol Heart Circ Physiol. 2025 Sep 1;329(3):H696-H704. doi: 10.1152/ajpheart.00534.2025. Epub 2025 Aug 13.


DOI:10.1152/ajpheart.00534.2025
PMID:40803714
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12409817/
Abstract

Patients with chronic kidney disease (CKD) are at an increased risk for vascular calcification (VC), a strong predictor of cardiovascular events. Rodent models with elevated dietary levels of adenine and phosphate are commonly used to study CKD-induced VC; however, dietary composition, regimen duration, and reported outcomes vary widely across studies. Researchers customize high-adenine, high-phosphate (AdeHP) diets by adjusting phosphate levels and selecting specific phosphate salts as the phosphate source. In this observational study, we found that the selection and amount of phosphate salt used as the dietary phosphate source in an AdeHP mouse model of CKD-induced VC influence disease severity and survival in a sex-specific manner. Mice were fed a high-adenine diet for 6 wk to induce CKD, followed by an AdeHP diet containing either sodium (AdeHP-HNa) or calcium (AdeHP-HCa) based phosphate salts for up to six additional weeks to induce VC. Mice on the AdeHP-HCa diet exhibited worse kidney function and higher circulating phosphate levels compared with those on the AdeHP-HNa diet, with males showing more severe outcomes than females. However, mice on the AdeHP-HCa diet showed lower VC levels compared with those on the AdeHP-HNa diet, with males developing more calcification than females after 6 wk of the AdeHP regimen. Most importantly, a pronounced sex-dependent difference in survival was observed in males on the AdeHP-HNa diet, with only 16.67% surviving. These findings underscore the importance of phosphate salt selection and sex-specific variability in modeling CKD-induced VC with the AdeHP diet, providing key insights and considerations for preclinical studies. We identified that the type of phosphate salt used to increase dietary phosphate in the adenine-induced CKD mouse model of VC influences calcification severity, survival, renal function, and circulating phosphate levels in a sex- and time-specific manner, with males exhibiting more severe outcomes. These findings highlight the importance of selecting and reporting phosphate salts used to supplement custom-made diets to prevent animal mortality and effectively model CKD-induced VC.

摘要

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Phosphate salt selection affects mortality and vascular calcification in the adenine-induced chronic kidney disease mouse model.

Am J Physiol Heart Circ Physiol. 2025-9-1

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本文引用的文献

[1]
Non-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease.

Circ Res. 2025-2-14

[2]
Sex-Specific Changes in Cardiac Function and Electrophysiology During Progression of Adenine-Induced Chronic Kidney Disease in Mice.

J Cardiovasc Dev Dis. 2024-11-7

[3]
Etelcalcetide ameliorates bone loss in chronic kidney disease-mineral and bone disorder by activation of IRF7 and necroptosis pathways.

Int J Biol Macromol. 2024-9-24

[4]
Role of sphingolipid metabolism signaling in a novel mouse model of renal osteodystrophy based on transcriptomic approach.

Chin Med J (Engl). 2025-1-5

[5]
Activation of PERK/eIF2α/ATF4/CHOP branch of endoplasmic reticulum stress response and cooperation between HIF-1α and ATF4 promotes Daprodustat-induced vascular calcification.

Front Pharmacol. 2024-7-31

[6]
Comparative Analysis of Vascular Calcification Risk Factors in Pre-Hemodialysis and Prevalent Hemodialysis Adult Patients: Insights into Calcification Biomarker Associations and Implications for Intervention Strategies in Chronic Kidney Disease.

Diagnostics (Basel). 2024-4-17

[7]
Recovery of Water Homeostasis in Adenine-Induced Kidney Disease Is Mediated by Increased AQP2 Membrane Targeting.

Int J Mol Sci. 2024-3-19

[8]
Extracellular histones promote calcium phosphate-dependent calcification in mouse vascular smooth muscle cells.

J Biochem. 2024-5-31

[9]
Effect of chronic kidney disease induced calcification on peripheral vascular perfusion using near-infrared spectroscopic imaging.

Biomed Opt Express. 2023-12-18

[10]
PRMT3 methylates HIF-1α to enhance the vascular calcification induced by chronic kidney disease.

Mol Med. 2024-1-10

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