Serum Phosphate Levels and Mortality in Incident Hemodialysis Patients: A National Retrospective Cohort Study

Abstract

Objectives

Mineral and bone disorders are frequent in patients in hemodialysis (HD) but a definite association of serum phosphate levels with mortality in this population is still an unmet issue. We assessed the association of three phosphate-level ranges with mortality in incident HD patients.

Methods

This national registry-based retrospective cohort study included 6214 incident adult patients on HD for >3 months. Data were collected from January 2011 to December 2018. The serum phosphate levels, represented by the median levels over the course of the entire HD treatment, were stratified into 3 ranges: <3.5 mg/dL, 3.5-5.5 mg/dL, and >5.5 mg/dL. The main outcome was 4-year all-cause mortality.

Results

The frequencies of cases in the lower, intermediate, and higher phosphate ranges were 5.8%, 64.6%, and 29.6%, respectively. In the fully adjusted multivariate model, the higher adopted phosphate range but not the lower one showed a significant association with mortality (hazard ratio [HR]: 1.54, 95% confidence interval [95% CI]: 1.21-1.95, P< .001). In the model, sevelamer, alone (HR: 0.44, 95% CI: 0.32-0.60, P< .001) or in combination with calcium-based phosphate binders (HR: 0.63, 95% CI: 0.40-0.98, P= .041), proved protective. In subgroup analyses, the lower adopted phosphate range was significantly associated with mortality only in patients <60 years. In a sensitivity analysis, we evaluated the effect of incremental intervals of 0.5 mg/dL across the phosphate distribution (from <2.0 mg/dL to ≥8.0 mg/dL), when serum phosphate <2.0 mg/dL was strongly associated with mortality (HR: 21.9, 95% CI: 2.99-160.66, P= .002).

Conclusion

The study reinforced the association of high phosphate levels with mortality in incident HD patients. The use of sevelamer was associated with a lower mortality rate when compared to the use of calcium-based phosphate binders. The lower adopted phosphate range was only associated with mortality in patients <60 years. In a sensitivity analysis though, phosphate levels below 2.0mg/dl were strongly associated with mortality.