Serum 1,25-Dihydroxyvitamin D: An Outcome Prognosticator in Human Sepsis

In sepsis, the vitamin D active metabolite 1,25-dihydroxyvitamin D (1,25(OH)₂D) may play a crucial role by its action to produce cathelicidin and improve endothelial barrier function, such that a deficiency in 1,25(OH)₂D is associated with poor outcome. To test our hypothesis, we performed analysis of stored plasma samples from a prospective observational study in 91 patients with sepsis, age of 59.1+/−2.0 years, 52.7% females, and 11.0% deaths at 30 days. Vitamin D status, including 25-hydroxyvitamin D (25(OH)D), 1,25(OH)₂D, 24,25-dihydroxyvitamin D (24,25(OH)₂D), and parathyroid hormone (PTH), were measured daily over 3 days after hospital admission. At baseline, 1,25(OH)₂D was significantly different between survivors vs. non-survivors. But there was no significant difference in 25(OH)D, 24,25(OH)₂D, and PTH. In a multivariable binomial logistic regression model, age, total calcium and 1,25(OH)₂D were significant predictors of 30-day mortality. Kaplan Meier analysis showed that patients with mean 1,25(OH)₂D measured over 3 days of < = 13.6 pg/mL had 57.1% 30-day survival compared to 91.7% in patients with 1,25 (OH)₂D level >13.6 pg/mL (p<0.01). From repeated measures regression analysis, there was significant increase in 1,25(OH)₂D for increases in 25(OH)D in both survivors and non-survivors. However, compared to survivors, the low 25(OH)D in non-survivors was insufficient to account for the larger decrease in 1,25(OH)₂D, indicating a dysfunctional 1α-hydroxylase. Additionally, there was a significant negative correlation between PTH and 1,25(OH)₂D in both survivors and non-survivors, suggesting a severe impairment in the effect of PTH to increase renal 1α-hydroxylase activity. In conclusion, low 1,25(OH)₂D levels are associated with increased 30-day mortality in sepsis patients, likely due to impaired 25(OH)D hydroxylation and PTH insensitivity. Our data also suggest that the active metabolite 1,25(OH)₂D may be an important therapeutic target in the design of sepsis clinical trials. [ABSTRACT FROM AUTHOR]