Phosphate overload directly induces systemic inflammation and malnutrition as well as vascular calcification in...

Area of Science:

• Nephrology
• Cardiovascular Medicine
• Nutritional Science

Background:

• Hyperphosphatemia in chronic kidney disease (CKD) is linked to cardiovascular mortality via vascular calcification (VC).
• Malnutrition and inflammation are also associated with increased cardiovascular death risk in CKD patients.
• The impact of phosphate (Pi) overload on inflammation and malnutrition in CKD requires further investigation.

Purpose of the Study:

• To investigate the effects of dietary phosphate loading on the interplay between inflammation, malnutrition, and vascular calcification (VC) in CKD.
• To explore the potential of lanthanum carbonate in mitigating these effects.

Main Methods:

• Adenine-induced CKD rats were fed diets with varying phosphate (Pi) concentrations (0.3%–1.2%) for 8 weeks.
• Measurements included serum and tissue TNF-α, oxidative stress markers, body weight, serum albumin, urinary creatinine, VC, and survival rates.
• In vitro studies used cultured human vascular smooth muscle cells exposed to high Pi medium.

Main Results:

• CKD rats exhibited Pi concentration-dependent increases in TNF-α, oxidative stress, malnutrition, VC, and premature death, independent of kidney function.
• Lanthanum carbonate treatment effectively reversed most Pi overload-induced changes.
• High Pi medium directly elevated TNF-α expression in vascular smooth muscle cells before increasing osteochondrogenic markers.

Conclusions:

• Dietary Pi overload induces systemic inflammation, malnutrition, VC, and premature death in CKD.
• Serum Pi levels strongly correlate with inflammation, malnutrition, and VC extent.
• Inhibiting Pi loading or employing anti-inflammatory therapies may prevent malnutrition-inflammation-atherosclerosis syndrome in CKD.