Influence of 1,25-Dihydroxyvitamin D3 on Human Leukocyte Antigen-DR Expression, Macrophage Infiltration, and Graft Survival in Renal Allografts

Vitamin D plays an important role in the regulation of cellular growth and cell proliferation as well as exerting immunoregulatory activities. We sought to show the influence of vitamin D on renal graft survival. Among 102 patients, 40 were treated with vitamin D (group D) and the remaining 62 cases were not, forming a control group (group C). We studied human leukocyte antigen (HLA)-DR expression on tubules, interstitial cells, peritubular capillaries (PTCs), and evaluated macrophage infiltration of the interstitium and the PTCs. Compared to group C, group D patients showed fewer acute rejection episodes. Compared to group C patients group D patients showed significantly lower degrees of tubular and interstitial HLA-DR expression as well as interstitial and PTC macrophage infiltration. In addition in the PTC, HLA-DR expression was greater and therefore PTC destruction less in group D patients (P < .001). Twenty-seven (43.5%) of 62 group C patients lost their grafts at 29.2 +/- 15 months, whereas only 7/40 (17.5%) group D patients lost their grafts at 43.2 +/- 13 months. A significant difference was noted between the two groups in regard to the time of graft loss (P < .01). Testing vitamin D therapy along with several other covariates showed an independent effect on 5-year graft survival (P < .001). These data confirmed that vitamin D therapy shows an independent positive impact on long-term graft survival, which may be explained by its immunosuppressive effects of to reduce renal HLA-DR expression and renal macrophage infiltration and in turn mitigate PTC destruction. In conclusion, these results highlighted the potential use of vitamin D in renal allograft patients.