Effect of paricalcitol vs calcitriol on hemoglobin levels in chronic kidney disease patients: a randomized trial

Abstract

Background: Recent studies suggest that vitamin D deficiency represents an additional cofactor of renal anemia, with several mechanisms accounting for this relationship. In line with it, the administration of vitamin D or its analogues has been associated with an improvement of anemia. There are no data, however, about a direct effect of paricalcitol on hemoglobin (Hb) levels. Therefore, we conducted a study to determine whether paricalcitol, compared to calcitriol, improves anemia in patients with chronic kidney disease (CKD).

Methods: In this randomized trial 60 CKD patients stage 3b-5 and anemia (Hb levels: 10-12.5 g/dL) were assigned (1:1) to receive low doses of calcitriol (Group Calcitriol) or paricalcitol (Group Paricalcitol) for 6 months. All the patients had normal values of plasma calcium, phosphorus and PTH, a stable iron balance, and normal values of C-Reactive Protein. The primary endpoint was to evaluate the effects of the two treatments on Hb levels; the modifications in 24hr-proteinuria (UProt) were also evaluated.

Results: A significant Group x Time interaction effect was observed in the longitudinal analysis of Hb levels (F(1,172)=31.4, p<0.001). Subjects in Paricalcitol experienced a significant monthly increase of Hb levels equal to +0.16 g/dL [95% C.I. 0.10 to +0.22, p<0.001) while in Group Calcitriol, Hb decrease throughout the follow-up with an average monthly rate of -0.10 g/dL (95% C.I.: -0.17 to -0.04, p<0.001). In Group Paricalcitol, UProt was significantly reduced after 6 months [0.35 (0.1-1.2) vs 0.59 (0.2-1.6), p<0.01], whereas no significant difference emerged in Group Calcitriol. Plasma levels of calcium, phosphate, PTH and of inflammation markers remained in the normal range in both groups throughout the study.

Conclusions: Short-term exposure to paricalcitol results in an independent increase in Hb levels, which occurred with no modification of iron balance, inflammatory markers, and PTH plasma concentrations, and was associated with a decrease in UProt.

Trial registration: ClinicalTrials.gov NCT01768351.

Fig 1. Flow chart of patient selection.

Fig 2. Effects of calcitriol (Group Calcitriol, dashed lines) and paricalcitol (Group Paricalcitol, solid lines) on hemoglobin plasma levels throughout the study.

Data are expressed as means ± SD. Abbreviations: T0, baseline levels; T2, T4 and T6, values after 2, 4 and 6 months of follow-up with both drugs. * = p<0.05 (minimum value) vs T0; § = p<0.05 (minimum value) vs respective period of Group CALC

Fig 3. Effects of calcitriol (Group Calcitriol, dashed lines) and paricalcitol (Group Paricalcitol, solid lines) on urinary protein excretion/GFR ratio throughout the study.

Data are expressed as means ± SE. Abbreviations: T0, baseline levels; T2, T4 and T6, values after 2, 4 and 6 months of follow-up with both drugs.