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

Abstract

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 (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.

Figure 1.

Association between the 13-wk averaged serum intact parathyroid hormone (iPTH) values <1000 pg/ml in 32,317 maintenance hemodialysis (MHD) patients (excluding 1990 patients with PTH >1000 pg/ml) in the base calendar quarter and the logarithm of the risk ratio of all-cause mortality over 3 yr on the basis of a multivariable regression spline model, adjusted for case mix and malnutrition-inflammation complex syndrome (MICS). Dashed lines are 95% pointwise confidence levels.

Figure 2.

Association between the 13-wk averaged paricalcitol dosage <60 μg/wk administered to 33,758 MHD patients (excluding 549 patients who received >60 μg/wk) in the base calendar quarter and the logarithm of the risk ratio of all-cause mortality over 3 yr on the basis of a multivariable regression spline model, adjusted for case mix and MICS. Dashed lines are 95% pointwise confidence levels.

Figure 3.

Association between the paricalcitol index (ratio of the administered paricalcitol dosage to serum PTH) in 33,381 MHD patients with a paricalcitol index <200 (excluding 926 patients with a paricalcitol index >200 μg/wk per pg/ml) in the base calendar quarter and the logarithm of the risk ratio of all-cause mortality over 3 yr in a multivariable regression spline model, adjusted for case mix and MICS. Dashed lines are 95% pointwise confidence levels.

Figure 4.

Association between the four a priori selected groups of paricalcitol index in the base calendar quarter and the risk ratio of all-cause mortality over 3 yr in a multivariable proportional hazard model at three levels of adjustment: (1) Minimally adjusted, (2) adjusted for case mix, and (3) adjusted for case mix and MICS. Error bars indicate 95% confidence levels.