title: Very low protein diet enhances inflammation, malnutrition, and vascular calcification in uremic rats.
abstract: OBJECTIVE
  Clinical studies have shown that very low protein diet (VLPD) has negative effects on long-term survival. It remains unclear why VLPD induces premature death. The present study determined the underlying mechanism whereby VLPD exerts its harmful effects on uremic rats.
  
  
  METHODS
  Rats were divided into four groups and fed a normal diet or diets containing 0.3% adenine and low/normal protein with high/low phosphate. After 6 weeks, body weight, urinary biochemistry (creatinine and phosphate), serum biochemical parameters (urea, creatinine, fibroblast growth factor 23, albumin, and fetuin-A), systemic inflammatory markers (serum tumor necrosis factor-alpha and urinary 8-hydroxy-2'-deoxyguanosine), calcium content in the aorta, and serum calcium-phosphate precipitates were evaluated. Hepatic mRNA levels were also determined.
  
  
  RESULTS
  Rats fed the diet containing 0.3% adenine developed severe azotemia. Rats fed VLPD developed malnutrition (decreases in body weight, serum albumin and fetuin-A levels, and urinary creatinine excretion) and systemic inflammation (increases in serum tumor necrosis factor-α and urinary 8-hydroxy-2'-deoxyguanosine) independent of phosphate status. VLPD decreased the serum fetuin-A level and hepatic fetuin-A synthesis and increased serum calcium-phosphate precipitates, a marker of calciprotein particle. A high-phosphate diet induced arterial medial calcification, which was enhanced by VLPD. Serum calcium-phosphate precipitate levels were correlated with the degree of inflammation, malnutrition, and aortic calcium content. Dietary phosphate restriction prevented VLPD-enhanced vascular calcification, but could not halt inflammation and malnutrition induced by VLPD.
  
  
  CONCLUSIONS
  VLPD enhances inflammation, malnutrition, and vascular calcification in uremic rats, among which only vascular calcification is prevented by dietary phosphate restriction.
authors.affiliation: Department of Internal Medicine, Fukuoka Dental College Medical and Dental Hospital, Fukuoka, Japan; Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: ana65641@nifty.com.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Internal Medicine, Fukuoka Dental College Medical and Dental Hospital, Fukuoka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tokumoto
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Narihito
authors.initials: N
authors.lastname: Tatsumoto
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tsuruya
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.affiliation: Department of Internal Medicine, Fukuoka Dental College Medical and Dental Hospital, Fukuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ooboshi
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D053099:Azotemia / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D060748:Fetuins / Q000378:metabolism; D007249:Inflammation / Q000209:etiology* / Q000473:pathology*; D007677:Kidney Function Tests; D008099:Liver / Q000378:metabolism; D008297:Male; D044342:Malnutrition / Q000209:etiology* / Q000473:pathology*; D008903:Minerals / Q000378:metabolism; D016226:Phosphorus, Dietary; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000150:complications* / Q000473:pathology*; D061205:Vascular Calcification / Q000209:etiology* / Q000473:pathology*
chemical_list: D060748:Fetuins; D008903:Minerals; D016226:Phosphorus, Dietary; D012333:RNA, Messenger; D002118:Calcium
keywords: Fetuin-A; Inflammation; Malnutrition; Uremia; Vascular calcification; Very low protein diet