Role of Paricalcitol in Modulating the Immune Response in Patients with Renal Disease

Abstract

Introduction. The aim was to highlight the existence of a relationship between vitamin D deficiency, chronic inflammation, and proteinuria, by measuring neutrophil gelatinase associated lipocalin (NGAL) and common inflammatory markers after administration of paricalcitol, a vitamin D analog, in vivo and in vitro. Methods. 40 patients with end-stage chronic kidney disease (CKD) and secondary hyperparathyroidism and 40 healthy subjects were enrolled. Serum calcium, phosphorus, 25(OH)-vitamin D, parathyroid hormone (PTH), erythrocyte sedimentation rate, high-sensitivity C-reactive protein, interleukin- (IL-) 17, IL-6, IL-1β, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), plasmatic and urinary NGAL, and 24 h albuminuria and proteinuria were measured before and 24 h after an intravenous bolus of paricalcitol (5 mcg). Human peripheral blood mononuclear cells were isolated and stimulated with phytohaemagglutinin. NGAL, IL-1β, IL-17, IL-6, TNF-α, and IFN-γ were measured in the culture medium and in the 24 h urine collection. Results. 25(OH)-vitamin D was lower in CKD than in controls (p < 0.0001), while inflammatory markers were higher in CKD group (p < 0.0001). In vivo and in vitro studies showed a downregulation of NGAL, IL-17, IL-6, IL-1β, TNF-α, and IFN-γ after paricalcitol administration (p < 0.0001). Conclusions. 25(OH)-vitamin D regulates immune and inflammatory processes. Further studies are needed to confirm these data in order to improve the treatment of CKD patients.

Role of Vitamin D Status in Diabetic Patients with Renal Disease

“…Moreover, vitamin D represses the expression of cyclooxygenase (COX)-2 and upregulates the expression of 15-hydroxyprostaglandin dehydrogenase (15PGDH), the enzyme initiating prostaglandin catabolism, in this way reducing prostaglandin levels and suppressing the production of several proinflammatory cytokines [136,137]. The immunomodulatory action of vitamin D has been well demonstrated also in the study of Lucisano et al [138], where an acute paricalcitol supplementation induced a significant reduction of IL-17, IL-6, IL-1β, TNF-α and IFN-γ in a cohort of CKD patients.…”

Vitamin D Receptor: A Novel Therapeutic Target for Kidney Diseases

“…Lucisano et al . found that 25(OH)D 3 can regulate immune processes through down-regulation of IL-17, IL-6, and IFN-γ in cultured human peripheral blood mononuclear cells [ 133 ].…”

Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients

“…However, in one clinical study in patients with vascular inflammation, paricalcitol appeared to exert its effect rather selectively on T-helper cells by interfering with calcineurin-mediated responses [ 36 ]. Modulation of adaptive immune responses in CKD-patients has been demonstrated, reflected by reductions in several inflammatory markers of Th1- Th2 and Th17-responses [ 37 ]. Oblak et al [ 30 ] demonstrated treatment effects in a quite large interventional study of RTRs.…”