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Cardiovascular disease, and mainly coronary heart disease (CHD), is the leading cause of death in hemodialysis (HD) patients. Non-traditional risk factors may play an important role in this population. Arginase is known to contribute directly to atherosclerosis progression and to counteract the beneficial effects of nitric oxide. HD could be considered as an inflammatory condition. Inflammation contributes to atherosclerosis progression and influences both arginase and nitric oxide synthase expression. In the present study, serum arginase type I was evaluated as a marker of CHD in HD patients. The markers of inflammation interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were also assessed. Sixty-eight HD patients and 24 healthy volunteers were enrolled into the study. Twenty HD patients suffered from CHD confirmed with coronary angiography, while the remaining 48 HD patients were asymptomatic. Serum arginase type I, IL-6 and TNF-α were measured with ELISA. During 24 months follow-up, none of the asymptomatic subjects developed symptoms of CHD. IL-6 and TNF-α levels were increased in HD patients, but did not differ between HD patients with or without CHD. On the contrary, arginase levels did not differ between healthy subjects and HD patients, but were twice higher in HD patients with CHD than in HD patients without CHD (22.41 ± 15.47 ng/ml vs. 10.16 ± 8.13 ng/ml). Arginase type I may contribute to the pathogenesis of CHD in HD patients and its serum levels could be used as a marker of CHD in this population.

Vitamin D and its analogues proved to exert immunomodulatory effects. Paricalcitol is a vitamin D analogue that is safe. It has been used for years in the treatment of secondary hyperparathyroidism in hemodialysis patients and, importantly, it is less calcemic than vitamin D. In this study the immunomodulatory/anti-inflammatory properties of paricalcitol were evaluated in vitro.Ten healthy volunteers enrolled into the study. Peripheral blood mononuclear cells (PBMC) at a concentration of 10(6) cells per well were cultured for 48 h in the presence or not of lipopolysaccharide (LPS) (100 ng/ml) and in the presence or not of paricalcitol (10(-8) M). TNF-alpha and IL-8 were measured in the supernatants by ELISA.Basal TNF-alpha concentration (50.3 +/- 22 pg/ml) was reduced by paricalcitol (44.1 +/- 23.2 pg/ml). LPS increased TNF-alpha concentration (150.0 +/- 81.7 pg/ml), but paricalcitol reduced it (121.1 +/- 69.0 pg/ml). The effect of paricalcitol on IL-8 production was more profound. Basal IL-8 concentration (1926 +/- 455 pg/ml) was reduced by paricalcitol (1273 +/- 472 pg/ml). LPS increased IL-8 concentration (2361 +/- 385 pg/ml), but paricalcitol returned it to its basal level (1849 +/- 417 pg/ml).The in vitro inhibition of transforming growth factor alpha and interleukin 8 by paricalcitol confirms the immunomodulatory properties of this vitamin D analogue.

Acquired immunity is impaired in hemodialysis (HD) patients, and decreased T cell number may contribute. Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) are expressed in cells of the immune system and affect T cell development, homeostasis and proliferation. Serum levels of RANKL and OPG and their relation to blood T cell number were evaluated in HD patients. Thirty-four HD patients and 20 healthy controls participated in the study. Serum RANKL and OPG were measured by ELISA and T cell number was assessed by flow cytometry. Median RANKL concentration did not differ between HD patients and healthy volunteers (300.00 pmol/L; range, 3,340.00 vs. 330.00 pmol/L; range, 440.00 pmol/L; p = 0.528). Median OPG was markedly higher in HD patients than in healthy volunteers (13.12 ± 4.71 vs. 4.71 ± 0.93 pmol/L, p