Inflammation: a putative link between phosphate metabolism and cardiovascular disease

Area of Science:

• Nephrology
• Cardiology
• Biochemistry

Background:

• Western dietary habits increase phosphate intake, challenging physiological mineral buffering systems.
• Phosphate homeostasis is tightly regulated by hormones including FGF23, αKlotho, PTH, and calcitriol.
• Chronic kidney disease (CKD) patients exhibit severe phosphate derangements, correlating with high cardiovascular morbidity and mortality.

Purpose of the Study:

• To review the critical interactions between phosphate homeostasis, inflammation, vascular calcification, and cardiovascular disease (CVD).
• To elucidate the role of pro-inflammatory responses in hyperphosphatemia-related vascular calcification.
• To highlight fibroblast growth factor 23 (FGF23) as a key factor in inflammation and cardiovascular alterations.

Main Methods:

• Literature review focusing on the interplay of phosphate, inflammation, and vascular calcification.
• Analysis of emerging evidence linking phosphate disturbances to inflammation and CVD.
• Examination of FGF23's role beyond its phosphaturic effects.

Main Results:

• Elevated serum phosphate is linked to increased CVD risk in both CKD and general populations.
• Vascular calcification, particularly medial vascular calcification, is associated with phosphate levels and inflammation.
• FGF23 plays a critical role in the complex interplay between inflammation and cardiovascular changes.

Conclusions:

• Disturbances in phosphate homeostasis are intrinsically linked to inflammation and vascular calcification, contributing to CVD.
• Understanding these interactions is crucial for managing cardiovascular risk in CKD and beyond.
• FGF23 emerges as a significant mediator in the phosphate-inflammation-CVD axis.