Ratio of paricalcitol dosage to serum parathyroid hormone level and survival in maintenance hemodialysis patients.
OBJECTIVE
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.


METHODS
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 (mircrog/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.
Shinaberger
Christian S
CS
Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90509-2910, USA.
Kopple
Joel D
JD
Kovesdy
Csaba P
CP
McAllister
Charles J
CJ
van Wyck
David
D
Greenland
Sander
S
Kalantar-Zadeh
Kamyar
K
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000401:mortality; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D016016:Proportional Hazards Models; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000378:metabolism; D006435:Renal Dialysis / Q000401:mortality; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D015415:Biomarkers; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; C084656:paricalcitol