Medscape Medical News
Vitamin D Lowers Hepcidin Levels in CKD Patients
June 01, 2012
June 1, 2012 (Paris, France) — Vitamin D supplementation is safe and economic for patients with chronic kidney disease (CKD); it can also decrease the need for erythropoietin-stimulating agents and ward off anemia by decreasing hepcidin levels and increasing ferroportin levels.
A new study has confirmed the positive effects of vitamin D on hepcidin and ferroportin levels in the serum of patients with CKD and in healthy volunteers. Justine Bacchetta, MD, PhD, from the Centre de Référence des Maladies Rénales Rares, Service de Néphrologie et Rheumatologie Pédiatriques, Hôpital Femme Mère Enfant, Bron Cedex, France, presented the research here at the XLIX European Renal Association-European Dialysis and Transplant Association Congress.
The study by Dr. Bacchetta and colleagues was based on reports of improved hemoglobin levels and decreased erythropoietin-stimulating agents requirements after vitamin D repletion in patients with CKD. "The iron homeostasis factor hepcidin is emerging as a likely cause of resistance to erythropoietic-stimulating factor," she noted. Higher hepcidin levels are also seen in CKD patients with anemia.
In the trial, a single oral dose of ergocalciferol 100,000 IU was given to 7 healthy subjects (4 men and 3 women); mean age was 42 years (range, 27 to 63 years). Measurements of serum hepcidin were taken at baseline and at 24 and 72 hours.
There was a 50% decrease in the serum hepcidin of all the healthy donors 24 hours after a single oral dose of vitamin D 100,000 IU; this suppression persisted for 72 hours (P = .001).
Levels of the active metabolites of 25-hydroxy vitamin D and 1,25 dihydroxy vitamin D were also detected in the serum.
A decrease of hepcidin and ferritin mRNA in PBMCs after vitamin D administration was seen on rtPCR. Increased levels of ferroportin were detected in the PMBCs using immunohistochemistry staining.
Similar results were observed in the monocytes of CKD patients. After vitamin D administration, a 0.42-fold decrease in hepcidin transcription was seen in PBMCs and a 0.57-fold decrease was seen in monocytes taken from patients with CKD (P < .05 for both).
"This points to a direct effect of 1,25 dihydroxy vitamin D on hepcidin transcription," said Dr. Bacchetta.
Ferroportin was expressed, and membrane enhancement in HepG2 cells, the adherent population of the PBMCs, was seen on immunohistochemistry after treatment.
"For the first time, we have shown results, both in vitro and in vivo, indicating that vitamin D is a potent suppressor of hepcidin in humans. We propose that these findings provide a clinically relevant mechanism showing how vitamin D supplementation can improve anemia management in CKD patients," Dr. Bacchetta explained.
"Vitamin D therapy absolutely has a role in the treatment of patients with CKD," said Dr. Stenvinkel. "The majority of dialysis patients have vitamin D deficiency, even in countries like Portugal and Brazil with a lot of sunlight. We need to replenish those stores in patients. It is an important cornerstone of treatment."
"Even if we do not have data from intervention trials regarding its effect on mortality, we know from registry and observational studies that those who have vitamin D treatment do better. If administered at the right levels, vitamin D is a nonrisky treatment," Dr. Stenvinkel asserted