November 30, 2006 - New Published Data Show Mortality Risk Lower for Vitamin D2 Versus D3 Analog Among Hemodialysis Patients

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Editorial Insights

Valerie Panzarino, MD

Associate Professor

Division of Nephrology

University of South Florida College of Medicine

Tampa, Florida

This report contains important information for clinicians who are considering a vitamin D analog for secondary hyperparathyroidism in hemodialysis patients. New, published data not only substantiates the importance of vitamin D therapy to mortality, but identifies differences between D2 over D3 analogs favoring the D2 analog, and provides evidence for efficacy and safety of the newer D2 analog, doxercalciferol.¹

As we know, patients with stage five chronic kidney disease who are maintained on hemodialysis (HD) have a high risk of mortality from atherosclerotic cardiovascular disease (ASCVD), hypothesized to be partially related to malnutrition and inflammation.² Disordered mineral metabolism has also been postulated to play an important role in the pathogenesis of ASCVD.^3,4 Serum calcium, phosphorus, and parathyroid hormone abnormalities have been shown to be associated with increases in all-cause and ASCVD mortality and morbidity of ∼17-20% compared to other mortality risks, such as inefficient dialysis or anemia.^5-7

Vitamin D deficiencies usually appear in earlier, stage two kidney disease, but worsen as kidney function declines.² According to NKF KDOQI Guidelines, intravenous vitamin D should be a mainstay of therapy among hemodialysis patients.⁹ Three products are currently available for this indication.^10-12  Calcitriol, the first available vitamin D analog (D3), was originally designed to treat hypocalcemia, but has been shown to effectively lower serum PTH. However, by stimulating intestinal calcium absorption, calcitriol also raises serum calcium and accelerates bone resorption.^8,9 When it is used together with calcium-based phosphorus binders or dialysate with high calcium concentrations, calcitriol may increase the risk for hypercalcemia,⁹ and possibly coronary artery calcification.^13,14

Vitamin D3 analog, calcitriol, when used in conjunction with calcium-based phosphate binders or dialysate with high calcium concentrations, may increase the risk for hypercalcemia, and possibly coronary artery calcification. 

Two vitamin D2 analogs became available more recently.^11,12  Paricalcitol and doxercalciferol are similar to calcitriol in their ability to lower PTH, but have more modest effects on serum calcium and phosphorus that the authors Tentori and colleagues discuss in more detail.^1,11-12

Previous studies have shown lower mortality rates with paricalcitol over the older calcitriol. Tentori et al investigated mortality associated with each vitamin D analog (calcitriol, paricalcitol, doxercalciferol) in a large cohort of patients starting hemodialysis at a large dialysis provider.

Over an extended examination period from 1999 to 2004, of almost 15,000 patients starting hemodialysis during the study period, 7731 patients were included who survived 30 days or more after the first vitamin D administration.  After a median follow-up of 37 weeks, the authors found that mortality rates (deaths/100 patient-years) were identical in patients on doxercalciferol and paricalcitol. Patients receiving calcitriol had higher mortality, and mortality was higher still in patients who did not receive a vitamin D analog. In all models comparing the two D2 analogs, doxercalciferol and paricalcitol, the estimates for hazard ratios were virtually 1.0. Another clinically significant finding from Tentori’s analysis is that differences in mortality between the D2 and D3 vitamin analogs may be smaller than prior reports have indicated.

Tentori and colleagues found that patients who did

not receive any vitamin D had the highest mortality.

This study, while retrospective in design, points to possible important considerations regarding as-yet uncharacterized covariates that might explain the differences in survival associated with the three vitamin D analogs. —NNF—

The University of South Florida College of Medicine wishes to acknowledge the support of Genzyme Corporation, which has provided an educational grant for this CE activity.

This publication is intended for physicians, dietitians, PAs, and other healthcare providers who care for and treat CKD patients.

Disclosure of faculty and commercial support relationships is required of the contributors to this CE activity. The following relationships have been disclosed:

Valerie Panzarino, MD, Associate Professor in the Division of Nephrology  at the  University of South Florida College of Medicine — Nothing to disclose.

Maria B. Uravich, ELS, CME Specialist with USF Office of Continuing Professional Development, (CME Reviewer) — Nothing to disclose.

Barbara Jones, ImpartMed — Nothing to disclose.

John Andrews, Scientific News International, Inc. — Nothing to disclose.

Shamera Rye, Scientific News International, Inc. — Nothing to disclose.

Off-Label Investigational Use Disclosure

Some of the information contained herein may cite the off-label use of drugs. Consult the approved package insert(s) for complete prescribing information.This CME activity was planned and produced in accordance with the ACCME Essential Areas and Policies.

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