title: Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis.
abstract: BACKGROUND
  Biochemical markers of altered mineral metabolism have been associated with increased mortality in end stage renal disease patients. Several studies have demonstrated non-linear (U-shaped or J-shaped) associations between these minerals and mortality, though many researchers have assumed linear relationships in their statistical modeling. This analysis synthesizes the non-linear relationships across studies.
  
  
  METHODS
  We updated a prior systematic review through 2010. Studies included adults receiving dialysis and reported categorical data for calcium, phosphorus, and/or parathyroid hormone (PTH) together with all-cause mortality. We performed 2 separate meta-analyses to compare higher-than-referent levels vs referent and lower-than-referent levels vs referent levels.
  
  
  RESULTS
  A literature review showed that when a linear relationship between the minerals and mortality was assumed, the estimated associations were more likely to be smaller or non-significant compared to non-linear models. In the meta-analyses, higher-than-referent levels of phosphorus (4 studies, RR = 1.20, 95% CI = 1.15-1.25), calcium (3 studies, RR = 1.10, 95% CI = 1.05-1.14), and PTH (5 studies, RR = 1.11, 95% CI = 1.07-1.16) were significantly associated with increased mortality. Although no significant associations between relatively low phosphorus or PTH and mortality were observed, a protective effect was observed for lower-than-referent calcium (RR = 0.86, 95% CI = 0.83-0.89).
  
  
  CONCLUSIONS
  Higher-than-referent levels of PTH, calcium, and phosphorus in dialysis patients were associated with increased mortality risk in a selection of observational studies suitable for meta-analysis of non-linear relationships. Findings were less consistent for lower-than-referent values. Future analyses should incorporate the non-linear relationships between the minerals and mortality to obtain accurate effect estimates.
authors.affiliation: Cerner Research, Culver City, CA, USA. jaime.natoli@hotmail.com
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Natoli
authors.forename: Rob
authors.initials: R
authors.lastname: Boer
authors.forename: Brian H
authors.initials: BH
authors.lastname: Nathanson
authors.forename: Ross M
authors.initials: RM
authors.lastname: Miller
authors.forename: Silvia
authors.initials: S
authors.lastname: Chiroli
authors.forename: William G
authors.initials: WG
authors.lastname: Goodman
authors.forename: Vasily
authors.initials: V
authors.lastname: Belozeroff
mesh_terms: D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality*; D010281:Parathyroid Hormone / Q000097:blood*; D010758:Phosphorus / Q000097:blood*
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone; D010758:Phosphorus; D002118:Calcium