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

Shunsuke Yamada, Masanori Tokumoto, Narihito Tatsumoto, Masatomo Taniguchi, Hideko Noguchi, Toshiaki Nakano, Kosuke Masutani, Hiroaki Ooboshi, Kazuhiko Tsuruya, Takanari Kitazono

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Hyperphosphatemia contributes to increased cardiovascular mortality through vascular calcification (VC) in patients with chronic kidney disease (CKD). Malnutrition and inflammation are also closely linked to an increased risk of cardiovascular death in CKD. However, the effects of Pi overload on inflammation and malnutrition remain to be elucidated. The aim of the present study was to investigate the effects of dietary Pi loading on the interactions among inflammation, malnutrition, and VC in CKD. We used control rats fed normal diets and adenine-induced CKD rats fed diets with different Pi concentrations ranging from 0.3% to 1.2% for 8 wk. CKD rats showed dietary Pi concentration-dependent increases in serum and tissue levels of TNF-α and urinary and tissue levels of oxidative stress markers and developed malnutrition (decrease in body weight, serum albumin, and urinary creatinine excretion), VC, and premature death without affecting kidney function. Treatment with 6% lanthanum carbonate blunted almost all changes induced by Pi overload. Regression analysis showed that serum Pilevels closely correlated with the extent of inflammation, malnutrition, and VC. Also, in cultured human vascular smooth muscle cells, high-Pi medium directly increased the expression of TNF-α in advance of the increase in osteochondrogenic markers. Our data suggest that dietary Pi overload induces systemic inflammation and malnutrition, accompanied by VC and premature death in CKD, and that inhibition of Pi loading through dietary or pharmacological interventions or anti-inflammatory therapy may be a promising treatment for the prevention of malnutrition-inflammation-atherosclerosis syndrome.

Original languageEnglish (US)
Pages (from-to)F1418-F1428
JournalAmerican Journal of Physiology - Renal Physiology
Volume306
Issue number12
DOIs
StatePublished - Jun 15 2014

Keywords

  • Chronic kidney disease
  • Inflammation
  • Malnutrition
  • Malnutrition-inflammation-atherosclerosis syndrome
  • Phosphate
  • Vascular calcification

ASJC Scopus subject areas

  • Physiology
  • Urology

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    Yamada, S., Tokumoto, M., Tatsumoto, N., Taniguchi, M., Noguchi, H., Nakano, T., Masutani, K., Ooboshi, H., Tsuruya, K., & Kitazono, T. (2014). Phosphate overload directly induces systemic inflammation and malnutrition as well as vascular calcification in uremia. American Journal of Physiology - Renal Physiology, 306(12), F1418-F1428. https://doi.org/10.1152/ajprenal.00633.2013