Date Published: September 6, 2019
Publisher: Public Library of Science
Author(s): Masashi Miyoshi, Yusuke Inoue, Mai Nishioka, Akishige Ikegame, Takayuki Nakao, Seiji Kishi, Toshio Doi, Kojiro Nagai, Justyna Gołębiewska.
Presepsin, a glycoprotein produced during bacterial phagocytosis, is used as a sepsis marker for bacterial infections. However, presepsin levels are affected by renal function, and the evaluation criteria according to kidney function or in chronic kidney diseases remain controversial. Furthermore, presepsin may be increased by sample stirring, but no studies have evaluated this effect.In this study, we excluded the effect of stirring by standardizing the blood collection conditions, analyzed the influence of kidney function on presepsin concentrations, and recalculated the reference range based on the findings. EDTA-whole blood from 47 healthy subjects and 85 patients with chronic kidney disease was collected to measure presepsin by PATHFAST. Presepsin was found to be significantly correlated with the levels of creatinine (r = 0.834), eGFRcreat (r = 0.837), cystatin-C (r = 0.845), and eGFRcys (r = 0.879). Furthermore, in patients with CKD, presepsin levels stratified by eGFRcys showed a significant increase in the CKD G2 patient group and with advancing glomerular filtration rate stage. The following values were obtained: Normal: 97.6 ± 27.4 pg/mL, CKD G1: 100.2 ± 27.6 pg/mL, CKD G2: 129.7 ± 40.7 pg/mL, CKD G3: 208.1 ± 70.2 pg/mL, CKD G4: 320.2 ± 170.1 pg/mL, CKD G5: 712.8 ± 336.3 pg/mL. The reference range, calculated by a nonparametric method using 67 cases of healthy volunteers and patients with chronic kidney disease G1, was found to be 59–153 pg/mL, which was notably lower than the standard reference range currently used. Presepsin concentrations were positively correlated with a few biomarkers of renal function, indicating the necessity to consider the effect of renal function in patients with renal impairment. Using the recalculated reference range considering kidney function may improve the accuracy of evaluating presepsin for diagnosis of sepsis compared to the standard reference currently in use.
Presepsin is a protein whose blood concentrations increase specifically during sepsis. Since its discovery in 2002 in Japan, presepsin has been widely used as a sepsis marker. Membrane-bound CD14, a surface antigen expressed on the cell membrane of monocyte macrophages and granulocytes, is a receptor for bacterial lipopolysaccharide (LPS), which activates cells via Toll-like receptor 4 . Additionally, soluble CD14 present in the blood induces the activation of endothelial and epithelial cells without membrane-bound CD14  and plays an important role in sensing invasion of bacteria in vivo. Recently, it was reported that granulocyte-mediated bacterial phagocytosis triggers elastase or cathepsin D to proteolytically cleave CD14 to produce presepsin and release it into the blood . Furthermore, it was shown that the concentration of presepsin increases with infection in patients with leucopenia , indicating that cells other than monocytes can trigger presepsin production.
Presepsin levels are affected by altered renal function and sample agitation. However, in previous studies, the effects of agitation were not considered, and the possibility of a false high level could not be excluded.