Disordered mineral metabolism in hemodialysis patients: an analysis of cumulative effects in the Hemodialysis (HEMO) Study.
BACKGROUND
Serum markers of disordered mineral metabolism have been associated with adverse outcomes in patients requiring long-term dialysis therapy. Although the values of these markers often evolve over time, no study has examined the accumulated effects of these abnormalities on important clinical end points.


METHODS
Retrospective cohort study.


METHODS
1,846 prevalent hemodialysis patients randomly assigned in the Hemodialysis (HEMO) Study.


METHODS
Serum phosphorus, calcium, calcium-phosphorus (Ca x P) product, and intact parathyroid hormone, each analyzed at the time of randomization (baseline), as a standard time-dependent covariate and as a cumulative time-dependent covariate.


RESULTS
All-cause mortality and the composite of all-cause mortality and first cardiac hospitalization.


METHODS
Cox proportional hazards models.


RESULTS
In all analyses, serum phosphorus level greater than 6 mg/dL was associated with a heightened risk of mortality of approximately 25% compared with phosphorus values of 4.1 to 5 mg/dL. Serum calcium level greater than 11 mg/dL was associated with a 60% greater risk of death, but only when this parameter was analyzed as either a time-dependent or cumulative time-dependent variable. Ca x P product greater than 50 mg(2)/dL(2) was strongly associated with mortality, but only when assessed cumulatively. Similar relationships were observed when phosphorus, calcium, and Ca x P product values were related to the composite end point of all-cause mortality and first cardiac hospitalization. No relationships between baseline, time-dependent, and cumulative time-dependent intact parathyroid hormone levels and the outcomes of interest were observed.


CONCLUSIONS
Residual confounding, lack of access to patient information before randomization in the HEMO Study, and concerns regarding generalizability given changes in practice patterns since the completion of the HEMO Study.


CONCLUSIONS
Cumulative time-dependent analyses provide a different framework for analyzing the impact of factors that may mediate adverse events in hemodialysis patients. Our findings support maintaining serum phosphorus levels at less than 6 mg/dL, calcium levels at less than 11 mg/dL, and Ca x P product at less than 50 mg(2)/dL(2).
Wald
Ron
R
Division of Nephrology and The Keenan Research Centre in the Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada. ron.wald@utoronto.ca
Sarnak
Mark J
MJ
Tighiouart
Hocine
H
Cheung
Alfred K
AK
Levey
Andrew S
AS
Eknoyan
Garabed
G
Miskulin
Dana C
DC
D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism; D002128:Calcium Metabolism Disorders / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D054559:Hyperphosphatemia / Q000209:etiology; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology*; D008875:Middle Aged; D008903:Minerals / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000378:metabolism; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects* / Q000401:mortality; D012189:Retrospective Studies
D008903:Minerals; D010281:Parathyroid Hormone; D010710:Phosphates; D002118:Calcium