25(OH)D and 1,25(OH)D vitamin D fails to predict sepsis and mortality in a prospective cohort study

Franz Ratzinger,Heinz Burgmann,Ralf L J Schmidt,Helmuth Haslacher,Rodrig Marculescu,Thomas Perkmann,Klaus G Schmetterer,Markus Stadlberger,Markus Obermüller,Athanasios Makristathis

doi:10.1038/srep40646

Abstract

The clinical role of vitamin D in sepsis and mortality prediction is controversially discussed. Therefore, we conducted a prospective cohort study on standard care wards, including 461 patients with suspected sepsis fulfilling two or more SIRS criteria. On the first and third day after onset of SIRS symptoms levels of 25(OH)D, 1,25(OH)D and sepsis biomarkers were analysed for their predictive capacity for identifying infection, bacteraemia and an elevated mortality risk. Additionally, several SNPs associated with vitamin D metabolism were evaluated. Bacteraemic patients (28.5%) presented with significantly lower 1,25(OH)D levels than SIRS patients without bacteraemia on the first and third day, while 25(OH)D did not show a predictive capacity. No significant differences of either 1,25(OH)D or 25(OH)D levels were found between SIRS patients with and without infections or between survivors and non-survivors. Sepsis biomarkers, including procalcitonin and CRP, showed a significantly higher discriminatory capacity for these classification tasks. The vitamin D metabolism-related SNPs analysed did not indicate any association with our outcome measures. In conclusion, 1,25(OH)D but not 25(OH)D showed a minor discriminatory value for the prediction of bacteraemia that was inferior to CRP and PCT but both failed to predict sepsis and mortality in a prospective cohort of SIRS patients.

Highlights

Vitamin D exhibits a plethora of effects on the innate and adaptive immune responses, endothelial function and the mucosal barrier[1]
We analysed the distribution of various single nucleotide polymorphisms, which are identified as being relevant for the vitamin D metabolism by genome-wide association studies (GWAS26–32)
A median 25(OH)D level of 28.3 nmol/L (16.7–51.8) was found on the first day after onset of SIRS symptoms and 28.7 nmol/L (16.8–49.9) on the third day after onset of SIRS symptoms, with a strong correlation between both time points

Summary

Introduction

Vitamin D exhibits a plethora of effects on the innate and adaptive immune responses, endothelial function and the mucosal barrier[1]. According to the recommendations of the Endocrine Society, 25(OH)D levels below 20 ng/ml (50 nmol/L) are defined as vitamin D deficiency and 25(OH)D levels of 21–29 ng/ml (52.5–72.5 nmol/L) as vitamin D insufficiency[9] From this pool of relatively inactive 25(OH)D, many cell types, including those of the immune system, have the ability to synthesize the highly active, but short-lived 1,25-dihydroxy-vitamin D (1,25(OH)D) by regulated expression of the CYP27B1 hydroxylase. 1,25(OH)D impacts metabolic pathways of dendritic cells and impedes their differentiation and maturation[21] Based on these findings, several clinical studies were conducted to evaluate whether vitamin D might be used as a diagnostic/ predictive marker or even as potential therapeutic target during infections. We analysed the distribution of various single nucleotide polymorphisms, which are identified as being relevant for the vitamin D metabolism by genome-wide association studies (GWAS26–32)

Methods

Results

Conclusion