Oral Cholecalciferol Supplementation in Sahara Black People with Chronic Kidney Disease Modulates Cytokine Storm, Oxidative Stress Damage and Athero-Thromboembolic Risk

Abstract

The 25-hydroxyvitamin D3 (25OHD3) deficiency in chronic kidney disease (CKD) is associated with immune system dysfunction (pro-inflammatory cytokines storm) through macrophages renal infiltration, oxidative stress (OxS) damage and athero-thromboembolic risk. Conversely, cholecalciferol supplementation (25OHD-S) prevents kidney fibrosis by inhibition of vascular calcification and nephrotic apoptosis (nephrons reduction). The objective of this study was to investigate the pleiotropic effects of 25OHD-S on immunomodulation, antioxidant status and in protecting against thromboembolic events in deficiency CKD Black and White individuals living in the Southern Sahara (SS). The oral 25OHD-S was evaluated in 60,000 IU/month/36 weeks versus in 2000 IU/day/24 weeks in Black (n = 156) and White (n = 150). Total serum vitamin D was determined by liquid chromatography-tandem mass spectrometry. All biomarkers of pro-inflammatory cytokines (PIC) were assessed by ELISA tests. OxS markers were assessed by Randox kits. Homocysteine and lipoproteine (a) were evaluated by biochemical methods as biomarkers of atherothromboembolic risk. All statistical analyses were performed with Student’s t-test and one-way ANOVA. The Pearson test was used to calculate the correlation coefficient. The means will be significantly different at a level of p value < 0.05. Multiple logistic regressions were performed using Epi-info and Statview software. Vitamin D deficiency alters the PIC profile, OxS damage and atherothrombogenic biomarkers in both SS groups in the same manner; however, these disorders are more acute in Black compared to White SS individuals. The results showed that the serum 25OHD3 concentrations became normal (>75 nmol/L or >30 ng/mL) in the two groups. We have shown that the dose and duration of 25OHD-S treatment are not similar in Black SS residents compared to White SS subjects, whilst the same inhabit the south Sahara environment. It appears that a high dose intermittent over a long period (D60: 36 weeks) was more efficient in Black people; while a lower dose for a short time is sufficient (D2: 24 weeks) in their White counterparts. The oral 25OHD-S attenuates PIC overproduction and OxS damage, but does not reduce athero-thromboembolic risk, particularly in Black SS residents.