ASSOCIATION OF SERUM PHOSPHORUS AND CALCIUM X PHOSPHATE PRODUCT WITH MORTALITY RISK IN CHRONIC-HEMODIALYSIS PATIENTS - A NATIONAL STUDY

Elevated serum phosphorus is a predictable accompaniment of end-stage renal disease (ESRD) in the absence of dietary phosphate restriction o r supplemental phosphate binders. The consequences of hyperphosphatemi a include the development and progression of secondary hyperparathyroi dism and a predisposition to metastatic calcification when the product of serum calcium and phosphorus (Ca x PO4) is elevated. Both of these conditions may contribute to the substantial morbidity and mortality seen in patients with ESRD. We have analyzed the distribution of serum phosphorus in two large national, random, cross-sectional samples of hemodialysis patients who have been receiving dialysis for at least 1 year. Data were obtained from two special studies of the United States Renal Data System, the Case Mix Adequacy Study (1990) and the Dialysi s Morbidity and Mortality Study Wave 1 (1993). The relative risk of de ath by serum phosphorus quintiles is described after adjusting for age at onset of ESRD, race, sex, smoking status, and the presence of diab etes, the acquired immunodeficiency syndrome, and/or neoplasm, Logisti c regression analysis is then used to describe the demographic, comorb id, and laboratory parameters associated with high serum phosphorus. S erum phosphorus was similar in these two study populations and average d 6.2 mg/dL. Ten percent of patients had levels greater than 9 mg/dL a nd at least 30% of each group had serum phosphorus levels greater than 7 mg/dL. The adjusted relative risk of death by serum phosphorus leve l was not uniform across all quintiles, being constant below a level o f 6.5 mg/dL and increasing significantly above this level, The relativ e risk of death for those with a serum phosphorus greater than 6.5 mg/ dL was 1.27 relative to those with a serum phosphorus of 2.4 to 6.5 mg /dL. This increased risk was not diminished by statistical adjustment for coexisting medical conditions, delivered dose of dialysis, nutriti onal parameters, or markers of noncompliance, Evaluation of predictors of serum phosphorus greater than 6.5 mg/dL revealed in multivariate a nalysis that younger age at onset of ESRD, female sex, white race, dia betes, active smoking, and higher serum creatinine levels were all sig nificant predictors. Analysis of serum calcium revealed no correlation with relative risk of death, The Ca x PO4 product, however, showed a mortality risk trend similar to that seen with serum phosphorus alone. Those in the highest quintile of the Ca x PO4 product (>72 mg(2)/dL(2 )) had a relative mortality risk of 1.34 relative to those with produc ts of 42 to 52 mg(2)/dL(2). The relative mortality risk by log parathy roid hormone (PTH) level was elevated for patients with higher levels, but the mortality risk associated with hyperphosphatemia was Independ ent of PTH. For hemodialysis patients who have been receiving dialysis for at least 1 year, we conclude that a large percentage have a serum phosphorus level above 6.5 mg/dL and that this places them at increas ed risk of death. This increased risk is independent of PTH. The mecha nism(s) responsible for death is unknown, but may be related to an abn ormally high Ca x PO4 product. Although mechanisms are not clearly est ablished, this study supports the need for vigorous control of hyperph osphatemia to improve patient survival. (C) 1998 by the National Kidne y Foundation, Inc.