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


METHODS
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).


CONCLUSIONS
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.
Denver Nephrologists PC, Denver, Colorado;, †Center for Observational Research, Amgen, Inc., Seattle, Washington, ‡Outcomes Insights, Inc., Westlake Village, California.
Geoffrey A
GA
Block
Ryan D
RD
Kilpatrick
Kimberly A
KA
Lowe
Wenli
W
Wang
Mark D
MD
Danese
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D002118:Calcium / Q000097:blood; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D005260:Female; D017052:Hospital Mortality; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010641:Phenotype; D010710:Phosphates / Q000097:blood; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects* / Q000401:mortality; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D002118:Calcium