Vitamin D in Acute and Chronic Rejection of Transplanted Kidney

Abstract

Due to its nephroprotective and immunomodulatory properties, vitamin D is susceptible to have a protective role against acute and chronic renal graft rejection. Regarding acute rejection (AR), experimental studies have shown that vitamin D receptor (VDR) agonists attenuate CD4+ and CD8+ T-cell proliferation and their cytotoxic activity, decrease plasma cell differentiation, B-cell proliferation, IgG secretion and differentiation, as well as maturation and immunostimulatory capacity of dendritic cells (DCs). By limiting adaptative immune response and down-regulating DC, VDR agonists are thus susceptible to help in preventing AR. The immunomodulatory capacity of calcitriol observed in vitro has been confirmed in several animal models of transplantation without increasing the risk of infection. Some observational studies and small interventional trials in renal transplant recipients (RTR) support the potential protective role of active vitamin D against AR. Regarding chronic rejection, in addition to potentially inducing tolerogenic DCs, VDR agonists could also inhibit the production of chemokines, responsible for leukocytes infiltration in vessels allograft, and may down-regulate TGF-β pathway, which has a profibrotic activity. Other renoprotective effects of vitamin D, such as inhibition of renin angiotensin system and of NF-kB activation, may participate in the prevention of chronic allograft rejection. Although several studies have highlighted the potential nephroprotective role of vitamin D sufficiency and of VDR agonists in humans, very few studies have been performed in RTR. Three ongoing randomized controlled trials are testing native vitamin D in RTR and should help to precise the role of the vitamin D pathway in reducing (or not) the risk of acute and chronic allograft rejection.