CKD-mineral and bone disorder and risk of death and cardiovascular hospitalization in patients on hemodialysis

Abstract

Background and objectives: Parathyroid hormone, calcium, and phosphate have been independently associated with cardiovascular event risk. Because these parameters may be on the same causal pathway and have been proposed as quality measures, an integrated approach to estimating event risks is needed.

Design, setting, participants, & measurements: Prevalent dialysis patients were followed from August 31, 2005 to December 31, 2006. A two-stage modeling approach was used. First, the 16-month probabilities of death and composite end point of death or cardiovascular hospitalization were estimated and adjusted for potential confounders. Second, patients were categorized into 1 of 36 possible phenotypes using average parathyroid hormone, calcium, and phosphate values over a 4-month baseline period. Associations among phenotypes and outcomes were estimated and adjusted for the underlying event risk estimated from the first model stage.

Results: Of 26,221 patients, 98.5% of patients were in 22 groups with at least 100 patients and 20% of patients were in the reference group defined using guideline-based reference ranges for parathyroid hormone, calcium, and phosphate. Within the 22 most common phenotypes, 20% of patients were in groups with significantly (P<0.05) higher risk of death and 54% of patients were in groups with significantly higher risk of the composite end point relative to the in-target reference group. Increased risks ranged from 15% to 47% for death and from 8% to 55% for the composite. More than 40% of all patients were in the three largest groups with elevated composite end point risk (high parathyroid hormone, target calcium, and high phosphate; target high parathyroid hormone, target calcium, and high phosphate; and target high parathyroid hormone, target calcium, and target phosphate).

Conclusion: After adjusting for baseline risk, phenotypes defined by categories of parathyroid hormone, calcium, and phosphate identify patients at higher risk of death and cardiovascular hospitalization. Identifying common high-risk phenotypes may inform clinical interventions and policies related to quality of care.

Figure 1.

Population distribution according to CKD–mineral and bone disorder phenotypes. Ca, calcium; P, phosphate; PTH, parathyroid hormone.

Figure 2.

Hazard ratios (HRs) of death and the composite end point by CKD–mineral and bone disorder phenotype. The reference group is the target low PTH (PTH 150–300 pg/ml), target serum calcium (8.2–10.2 mg/dl), and target serum phosphate (3.5–5.5 mg/dl). Whiskers depict the 95% confidence intervals (95% CIs). Ca, calcium; P, phosphate; PTH, parathyroid hormone.