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

survival (days)

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.