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

Abstract

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.

Evaluation of two fully automated immunoassay based tests for the measurement of 1α,25-dihydroxyvitamin D in human serum and comparison with LC-MS/MS

“…Determination of 1,25(OH) 2 vitD can also be useful in patients with unexplained hyperparathyroidism who have adequate 25(OH) vitD levels. 1,25(OH) 2 vitD is particularly suitable to differentiate between two hereditary defects namely vitamin D-dependent rickets (VDDR) type I, caused by vitamin D 1α-hydroxylase deficiency, and VDDR type II, caused by mutation of the vitamin D receptor gene leading to end-organ resistance to vitamin D. The growing knowledge of the prognostic significance of 1,25(OH) 2 vitD after cardiac surgery and in sepsis and heart failure [11][12][13] will further increase the medical need to analyze 1,25(OH) 2 vitD.…”

Vitamin D Deficiency and Critical Illness

“…Vitamin D deficiency is associated with sepsis and mortality in critically ill adults [10]. There is some evidence that low vitamin D level is a predictor of mortality in septic individuals [11].…”

Effect of Vitamin D or Activated Vitamin D on Circulating 1,25-Dihydroxyvitamin D Concentrations: A Systematic Review and Metaanalysis of Randomized Controlled Trials

“…However, in addition to poor kidney function, diabetes mellitus, high concentrations of the inflammatory marker C-reactive protein, and high EuroScore values (a cardio-surgical risk marker) are also independently associated with low circulating 1,25(OH) 2 D concentrations (6 ). Some clinical studies indicate that circulating 1,25(OH) 2 D is a better predictor of short-term or midterm mortality than circulating 25OHD (7)(8)(9). Thus, the clinical relevance of circulating 1,25(OH) 2 D is probably underappreciated.…”