The Impact of Selective Vitamin D Receptor Activation on Clinical Outcomes in Septic Patients

Sufficient serum levels of vitamin D are important for immune system regulation with protective effect against severe infection and overactivated inflammatory response in sepsis. It is also not clear what level of vitamin D in the blood would be the trigger for vitamin D administration. A more selective approach to VDR activation than cholecalciferol could have a more significant role in the clinical outcomes of patients with sepsis. A study demonstrated that low baseline serum level of vitamin D receptor (VDR) was associated with a high incidence of 28-day mortality and negatively correlated with lactate, C-reactive protein, APACHE II SOFA scores, and disease severity among patients with sepsis in an ICU setting. The role of selective vitamin D receptor activation agents (paricalcitol or maxacalcitol) was not studied in septic patients, despite its anti-inflammatory and immunomodulatory properties. Vitamin D analogs have different effects on nuclear VDRs than does calcitriol, through different response elements in various target genes, so it is possible that their effect on a patient with sepsis will be more effective than cholecalciferol. As distribution of VDRs is ubiquitous in many organs and tissues, selective VDR activation with paricalcitol may have beneficial effects in preserving organs functionality and modulating the immune response in sepsis. Hypotheses 1. The immunoregulatory, anti-inflammatory, and anti-oxidative properties of selective vitamin D receptor activator paricalcitol would result in improvement of inflammatory, endothelial function, and antioxidative parameters and clinical outcomes in groups of septic patient admitted to ICU. 2. The baseline septic patient serum 25(OH) D3 levels at admission time in ICU have influence on clinical outcomes as well as on inflammatory, endothelial function, and antioxidative parameters. 3. The inflammatory, endothelial function, and antioxidative parameters measured at ICU admission time have significant impact on clinical outcomes in septic patients. The aim The main objective of study is to test hypothesis that that selective activator of vitamin D receptors paricalcitol will improve outcomes of septic patient admitted in ICU. The study aims to investigate the effects of paricalcitol on clinical outcomes, inflammatory markers, organ dysfunction, endothelial function, vascular morphology, coagulation markers, and haemodynamic parameters. The additional objectives of the study are to test hypothesis that septic patient serum 25(OH)vitamin D3 have impact on inflammatory, endothelial function, and antioxidative parameters including protein carbonylation; and to test hypothesis that these markers and clinical outcomes are interconnected with significant impact on clinical outcomes.