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Ratio of Paricalcitol Dosage to Serum Parathyroid Hormone Level and Survival in Maintenance Hemodialysis Patients

Christian S. Shinaberger^*,, Joel D. Kopple^,,||, Csaba P. Kovesdy^¶, Charles J. McAllister^**, David van Wyck^**,, Sander Greenland, and Kamyar Kalantar-Zadeh^*,,

^* Harold Simmons Center for Kidney Disease Research and Epidemiology; Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance; David Geffen School of Medicine and Departments of; Epidemiology; ^|| Family Health, School of Public Health, University of California, Los Angeles, Los Angeles; ^** DaVita, Inc., El Segundo, California; ^¶ Salem VA Medical Center, Salem, Virginia; and Departments of Medicine and Surgery, Arizona Center on Aging, Arizona Health Sciences Center, Tucson, Arizona

Correspondence: Dr. Kamyar Kalantar-Zadeh, Harold Simmons Center for Kidney Disease Research and Epidemiology, LABioMed at Harbor-UCLA Medical Center, 1124 West Carson Street, C1-Annex, Torrance, CA 90509-2910. Phone: 310-222-3891; Fax: 310-782-1837; E-mail: kamkal{at}ucla.edu

Background and objectives: Several observational studies have indicated that vitamin D receptor activators (VDRA), including paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients; however, patients with higher serum parathyroid hormone (PTH), indicative of a more severe secondary hyperparathyroidism and higher death risk, are usually given higher VDRA dosages, which can lead to confounding by medical indication and attenuated survival advantage of high VDRA dosages. It was hypothesized that the ratio of the administered paricalcitol dosage to serum PTH level discloses better the underlying dosage–survival association.

Design, setting, participants, & measurements: The 3-yr mortality predictability of the administered paricalcitol during the first 3 mo of the cohort divided by averaged serum intact PTH during the same period was examined in 34,307 MHD patients from all DaVita dialysis clinics across the United States using Cox regression.

Results: MHD patients were 60.8 ± 15.4 yr of age and included 47% women, 34% black patients, and 47% patients with diabetes. Initially, the ratio of paricalcitol (µg/wk) to PTH (pg/ml) was divided into four groups: 0 (reference), 1 to <30, 30 to <60, and >60 x 10^–3. Unadjusted, case mix–adjusted (demographics, comorbidity, and Kt/V), and malnutrition-inflammation complex syndrome–adjusted models, the death rate ratio for the paricalcitol/PTH index groups, were 0.99, 0.95, and 0.92. Restricted cubic splines analyses were consistent with a linear relation.

Conclusions: Higher weekly paricalcitol dosage per each unit of serum PTH seems to have an incremental association with greater survival in MHD patients. The observed dosage-response phenomenon needs to be confirmed in clinical trials.