STUDY OBJECTIVES: To determine if apparent protective mortality benefits of intravenous active vitamin D in patients undergoing hemodialysis extend across all groups defined by dialysis duration; if higher monthly dose and dosing regularity are associated with reduced mortality; and if intravenous active vitamin D use is associated with reduced cardiovascular, infectious, and cancer-related mortality. STUDY DESIGN: Retrospective cohort study. DATA SOURCE: Centers for Medicare and Medicaid Services End-Stage Renal Disease database. PATIENTS: A total of 193,830 patients undergoing hemodialysis during 1999-2000, of whom 94,208 (48.6%) were taking intravenous active vitamin D in the baseline period. MEASUREMENTS AND MAIN RESULTS: Time-varying Cox proportional hazards models were used to assess the effects of monthly vitamin D dose and dosing regularity over 3-month intervals on risk of all-cause and cause-specific death, by dialysis duration groups (<1 yr, 1 to <3 yrs, 3 to <5 yrs, and >or=5 yrs from dialysis initiation). Models were adjusted for baseline characteristics, time-varying hospital days, monthly epoetin alfa dose, mean hemoglobin level, and urea reduction ratio in the 3-month intervals. Maximum follow-up time was 5.25 years. Adjusted all-cause mortality risk was reduced 7-17% among patients receiving vitamin D each month of the 3-month interval, with the highest reduction among patients with shorter dialysis duration. However, regular vitamin D dosing did not show consistent benefit across dialysis duration groups for cardiovascular, infectious, cancer, or other (all deaths not attributable to cardiovascular disease, infection, or cancer) mortality. CONCLUSION: Mortality benefits of intravenous vitamin D cannot be easily explained by currently proposed biologic mechanisms. Randomized controlled trials are needed to show definitively whether intravenous vitamin D can reduce all-cause and cause-specific mortality in patients undergoing dialysis compared with placebo.
STUDY OBJECTIVES: To determine if apparent protective mortality benefits of intravenous active vitamin D in patients undergoing hemodialysis extend across all groups defined by dialysis duration; if higher monthly dose and dosing regularity are associated with reduced mortality; and if intravenous active vitamin D use is associated with reduced cardiovascular, infectious, and cancer-related mortality. STUDY DESIGN: Retrospective cohort study. DATA SOURCE: Centers for Medicare and Medicaid Services End-Stage Renal Disease database. PATIENTS: A total of 193,830 patients undergoing hemodialysis during 1999-2000, of whom 94,208 (48.6%) were taking intravenous active vitamin D in the baseline period. MEASUREMENTS AND MAIN RESULTS: Time-varying Cox proportional hazards models were used to assess the effects of monthly vitamin D dose and dosing regularity over 3-month intervals on risk of all-cause and cause-specific death, by dialysis duration groups (<1 yr, 1 to <3 yrs, 3 to <5 yrs, and >or=5 yrs from dialysis initiation). Models were adjusted for baseline characteristics, time-varying hospital days, monthly epoetin alfa dose, mean hemoglobin level, and urea reduction ratio in the 3-month intervals. Maximum follow-up time was 5.25 years. Adjusted all-cause mortality risk was reduced 7-17% among patients receiving vitamin D each month of the 3-month interval, with the highest reduction among patients with shorter dialysis duration. However, regular vitamin D dosing did not show consistent benefit across dialysis duration groups for cardiovascular, infectious, cancer, or other (all deaths not attributable to cardiovascular disease, infection, or cancer) mortality. CONCLUSION: Mortality benefits of intravenous vitamin D cannot be easily explained by currently proposed biologic mechanisms. Randomized controlled trials are needed to show definitively whether intravenous vitamin D can reduce all-cause and cause-specific mortality in patients undergoing dialysis compared with placebo.