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Phosphorus and non-atherosclerotic heart disease

Serum phosphorus has been linked to vascular calcification (VC),1-3 an important cause of vascular stiffness in CKD leading to increased pulse wave velocity, increased cardiac work, left ventricular hypertrophy, and decreased coronary artery blood flow. 3 Phosphorus has been further implicated as a cause of VC through studies in vitro that have demonstrated that it induces phenotypic changes in vascular smooth muscle cells (VSMC) by increasing gene transcription of proteins involved in osteoblast function–bone formation9 and stimulating matrix mineralization.4-6

Signs and Symptoms Deep cramping in the muscles

Diagnosis Laboratory values greater than 5.5 mg/dL, iPTH 500, imaging showing non-atherosclerotic heart disease

Etiology Inability to clear excess phosphorus from the diet due to chronic kidney disease

Treatment Low phosphorus diet alone or in combination with use of phosphorus binders to limit excess phosphorus in the blood to prevent increases in iPTH which can mobilize calcium from the bone.  Mortality The relative risk of death associated with a serum phosphorus level > 6.5 mg/dL is 1.27 compared with a serum phosphorus level of 2.4 mg/dL to 6.5 mg/dL. 8

References 1. Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL: Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 16 : 520 –528, 2005 2. London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H: Arterial media calcification in end-stage renal diseases: Impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 18 : 1731 –1740, 2003 3. Raggi P, Boulay A, Chasan-Taber S, Amin N, Dillon M, Burke SK, Chertow GM: Cardiac calcification in adult hemodialysis patients: A link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol 39 : 695 –701, 2002 4. Steitz SA, Speer MY, Curinga G, Yang H-Y, Haynes P, Aebersold R, Schinke T, Karsenty G, Giachelli CM: Smooth muscle cell phenotypic transition associated with calcification. Circ Res 89 : 1147 –1154, 2001 5. Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, Morii H, Giachelli CM: Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 87 : e10 –e17, 2000 6. Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, Jahnen-Dechent W, Weissberg PL, Shanahan CM: Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: A potential mechanism for accelerated vascular calcification in ESRD. 7. Circulation. Contemporary reviews in cardiovascular medicine. July 10, 2012 vol. 126 no. 2;213-222 8. Block GA, Hulbert-Sheraton TE, Levin NW, Port FK. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Disease. 1998;31:607-617