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

BMC Nephrol. 2013 Apr 17;14:88. doi: 10.1186/1471-2369-14-88.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Biomarkers / blood
  • Calcium / blood*
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / mortality*
  • Parathyroid Hormone / blood*
  • Phosphorus / blood*


  • Biomarkers
  • Parathyroid Hormone
  • Phosphorus
  • Calcium