Clinical evaluation of presepsin considering renal function

Abstract

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.

Biomarkers for Point-of-Care Diagnosis of Sepsis

“…Although this study was conducted in patients without any evidence of bacterial infection or sepsis, similar results have been demonstrated in septic patients with and without AKI [66], leading to the conclusion that PCT has much better diagnostic accuracy in patients with AKI than presepsin. An increase in presepsin was also noted in AKI patients without sepsis, in line with the finding of Miyoshi and co-workers [89]. It is important to ensure that the correct analytical target is measured; one study described the use of presepsin, but closer inspection revealed that they had actually measured soluble CD14 and not presepsin (soluble CD14 subtype) [90].…”

“…It is interesting to note that the 19 studies they reviewed were all observational; no randomised controlled trials were found, which resulted in the evidence being considered of low quality. Miyoshi and co-workers demonstrated that the concentration of presepsin is influenced by renal function, and that there is a correlation between declining renal function and increasing presepsin concentration [89]. Although this study was conducted in patients without any evidence of bacterial infection or sepsis, similar results have been demonstrated in septic patients with and without AKI [66], leading to the conclusion that PCT has much better diagnostic accuracy in patients with AKI than presepsin.…”

“…IL-6 correlated with SOFA, although it did not appear to be useful for predicting mortality. An early study also demonstrated a relationship between IL-6 and SOFA, but again, the use of IL-6 in predicting outcome was limited [89]. The most comprehensive review of the diagnostic potential of IL-6 was conducted by Molano Franco and co-workers [104] as part of the Cochrane Database of Systematic Reviews, which was based on 23 studies containing 4192 patients.…”

Presepsin as a Diagnostic and Prognostic Biomarker in Sepsis

“…A range of presepsin levels in the absence of acute pathology was established for individuals with normal renal function compared with patients with chronic renal failure. Individuals with grade 3, 4 and 5 renal failure had baseline presepsin values significantly above the other group, with values of 208.1 ± 70.2 pg/mL, 320.2 ± 170.1 pg/mL, 712.8 ± 336.3 pg/mL, respectively [54]. Three studies on patients presenting with acute kidney injury and sepsis indicated that in the validity of presepsin measurement in this population was reduced [55,56] and procalcitonin was superior as a diagnostic and prognostic marker of sepsis in this group [57].…”

<p>Presepsin Level Correlates with the Development of Moderate Coronary Artery Calcifications in Hemodialysis Patients: A Preliminary Cross-Section Design Study</p>

“…Presepsin is one of the new inflammatory markers and been found to inversely correlated with GFR. 17,19,20 Furthermore, in HD patients, presepsin levels are significantly higher than in grade 5 CKD patients. 17 Similarly, in the present study, the overall presepsin level in HD patients was 14 times higher than renal-healthy controls.…”