Although current activated vitamin D therapies are approved for secondary hyperparathyroidism treatment in chronic kidney disease (CKD), several experimental data confirm that vitamin D pleiotropic effects extend beyond mineral metabolism Lin R - 2003 [1] (Fig. 1) In addition to its role in calcium homeostasis and bone mineralization, in fact, vitamin D is involved in immune defence, cardiovascular function, inflammation and erythropoiesis Nagpal S - 2005 [2] (full text). In vitro studies of bone marrow red cell precursor cells demonstrate that vitamin D increases erythropoietin-receptor expression and synergistically stimulates proliferation along with erythropoietin Alon DB - 2002 [3]. In addition, vitamin D has anti-inflammatory actions that could theoretically improve erythropoietin responsiveness, perhaps by reducing interleukin-6 (IL-6) levels and thus levels of hepcidin Turk S - 2002 [4], and could ameliorate anemia by correcting the secondary hyperparathyroidism Neves PL - 2006 [5]. However, there are no data on the direct effect of oral paricalcitol, a newVitamin D Receptor activator, on the anemia in CKD.
Our study aims to determine whether the use of oral paricalcitol leads to improvement in anemia in CKD, and whether this effect is independent from hyperparathyroidism correction.
A total of 34 patients with CKD 3-5 stage not on dialysis (eGFR ≤60 ml/min/1.73 m2) and anemia (Hb 10--12,5 g/dl) were enrolled (Fig. 2). Patients with iron deficiency (ferritin <100 ng/ml; transferrin saturation <20%), severe iperparathyroidism (PTH >300 pg/ml) and inflammation (C-reactive protein >1mg/dL) were excluded. The enrolled patients were randomly assigned to receive either paricalcitol (CASE) or native vitamin D/calcitriol (CONTROL) for 6 months. The end point was the difference in Hb levels from the basal after 6 months of treatment (T3) in the two groups.
The patients of the case group (n=17) showed a significant increase in Hb levels after 6 months of therapy (p=0,03). In control group (n=17), Hb progressively decreased (p=0,01) (Fig. 3). Moreover, after only 2 months (T1) the difference in Hb levels between the groups was significant (p=0,012), and remained stable until the end of the study (p=0,015) (Fig. 4). No significant change was reported in PTH and PCR levels.
Oral paricalcitol could improve anemia in CKD patients. The increase in Hb levels is likely due to a direct stimulation of erythroid precursors as reported in vitro for calcitriol and it could be no related to hyperparatiroidism correction.
[1] Lin R, White JH The pleiotropic actions of vitamin D. BioEssays : news and reviews in molecular, cellular and developmental biology 2004 Jan;26(1):21-8
[2] Nagpal S, Na S, Rathnachalam R et al. Noncalcemic actions of vitamin D receptor ligands. Endocrine reviews 2005 Aug;26(5):662-87 (full text)
[3] Alon DB, Chaimovitz C, Dvilansky A et al. Novel role of 1,25(OH)(2)D(3) in induction of erythroid progenitor cell proliferation. Experimental hematology 2002 May;30(5):403-9
[4] Türk S, Akbulut M, Yildiz A et al. Comparative effect of oral pulse and intravenous calcitriol treatment in hemodialysis patients: the effect on serum IL-1 and IL-6 levels and bone mineral density. Nephron 2002 Feb;90(2):188-94
[5] Neves PL, Triviño J, Casaubon F et al. Elderly patients on chronic hemodialysis with hyperparathyroidism: increase of hemoglobin level after intravenous calcitriol. International urology and nephrology 2006;38(1):175-7
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