Dietary L-lysine prevents arterial calcification in adenine-induced uremic rats

J Am Soc Nephrol. 2014 Sep;25(9):1954-65. doi: 10.1681/ASN.2013090967. Epub 2014 Mar 20.


Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Alanine / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Arginine / pharmacology
  • Calcium / blood
  • Calcium / urine
  • Calcium Phosphates / metabolism
  • Cells, Cultured
  • Chemical Precipitation / drug effects
  • Creatinine / urine
  • Dietary Supplements
  • Homoarginine / pharmacology
  • Humans
  • Lysine / administration & dosage*
  • Lysine / blood
  • Lysine / pharmacology
  • Male
  • Metabolic Networks and Pathways / drug effects
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects
  • Osteoporosis / prevention & control
  • Proline / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Solutions
  • Uremia / chemically induced
  • Uremia / complications
  • Uremia / diet therapy*
  • Vascular Calcification / etiology
  • Vascular Calcification / metabolism
  • Vascular Calcification / prevention & control*


  • Calcium Phosphates
  • Solutions
  • Homoarginine
  • Arginine
  • calcium phosphate
  • Proline
  • Creatinine
  • Adenine
  • Lysine
  • Alanine
  • Calcium