title: Phosphate - the silent stealthy cardiorenal culprit in all stages of chronic kidney disease: a systematic review.
abstract: OBJECTIVE
  Due to increasing evidence suggesting a link between hyperphosphatemia and cardiovascular disease (CVD), mediated through vascular calcification in patients on dialysis, the following question arises: At what stage of chronic kidney disease (CKD) does the relationship between elevated phosphate levels, vascular calcification and increased cardiovascular mortality begin? Therefore, the purpose of the current study was to critically review the current literature regarding this issue.
  
  
  METHODS
  We performed a systematic search of the National Library of Medicine and the Cochrane Library databases from January 1985 to February 2008 to identify clinical studies examining the effects of plasma phosphate on cardiovascular outcome, mortality and progression of kidney disease in subjects with and without CKD who have not yet received dialysis. The primary outcome measure was the development of CVD, mortality and progression of kidney disease.
  
  
  RESULTS
  Twelve clinical trials investigated the role of serum phosphate levels and adverse outcome (9 studies examining CVD outcome and 3 examining progression of kidney disease). After adjustment for risk factors for mortality, adverse cardiovascular outcome and progression of kidney disease, all studies found a graded independent significant association between phosphate levels and mortality, development of CVD and progression of kidney disease. There was no such association with plasma calcium levels.
  
  
  CONCLUSIONS
  There is a graded independent association between serum phosphate levels and mortality, mainly cardiovascular events, and the progression of renal disease in subjects with and without definable (loss of glomerular filtration rate) CKD.
authors.affiliation: Department of Internal Medicine, Section of Nephrology, Fatih University School of Medicine, Istanbul, Turkey. mkanbay@fatih.edu.tr
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kanbay
authors.forename: David
authors.initials: D
authors.lastname: Goldsmith
authors.forename: Ali
authors.initials: A
authors.lastname: Akcay
authors.forename: Adrian
authors.initials: A
authors.lastname: Covic
mesh_terms: D002118:Calcium / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology; D018450:Disease Progression; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000401:mortality*; D010710:Phosphates / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000401:mortality; D012307:Risk Factors
chemical_list: D010710:Phosphates; D002118:Calcium