Plasma soluble receptor for advanced glycation end products (sRAGE) predicts survival in
critically ill patients with systemic inflammatory response syndrome or sepsis
Helena Brodska, Karin Malickova, Marta Kalousova and Tomas Zima
Institute of Clinical Biochemistry and Laboratory Diagnostics, General Teaching Hospital and 1st Faculty of Medicine of Charles University, Prague, Czech Republic
INTRODUCTION
RESULTS
Multiple biochemical markers have been
evaluated as a determinant of severity of organ
failure in sepsis, and were used for
prognostication of the outcome.
The soluble receptor for advanced glycation end
products (sRAGE) is a novel marker that has been
linked to end-stage renal disease, acute lung
injury and acute pancreatitis. Its role in patients
with systemic inflammatory response syndrome
(SIRS) or sepsis has not yet been fully
determined.
There were 39 survivors and 15 non-survivors.
On admission,
 38 patients had bacterial sepsis,
 9 patients had mycotic sepsis and
 7 patients had SIRS (unproven microbial
agent).
AIMS
We sought to determine whether sRAGE could be
used as a potential prognostic marker in these
patients. We assessed
¨
1) the correlation between sRAGE levels early
after admission and 28-day mortality, and
RESULTS
SURVIVORS
On day 1, non-survivors showed increased
sRAGE levels compared to survivors (median
[IQR]: 2711 [1035; 3823] pg/mL vs. 1055 [617;
1789] pg/mL respectively, p=0,027).
On day 3, the association of increased sRAGE
levels in non-survivors (5328 [4189;5707] pg/mL)
was even stronger when compared to survivors
(779 [523;2195]) (p=0.0004).
Unadjusted odds ratio for 28-day survival was
8.250 (95% CI 1.017;60.636) for sRAGE, p=0.048.
2) correlation of sRAGE with other biochemical
markers of organ failure in patients with
SIRS/sepsis.
MATERIALS AND METHODS
Fifty-four patients admitted to the intensive care
unit (ICU) with symptoms of SIRS/sepsis were
enrolled in a single-center prospective exploratory
study. The severity of a patient’s illness was
estimated using the APACHE II score.
Compared with sRAGE, no other measured
parameter showed so significant change during
days 1 - 3 in non-survivors.
Plasmatic levels of sRAGE, procalcitonin (PCT),
C-reactive protein (CRP) and creatinine were
assessed on days 1,2 and 3.
sRAGE showed a significant positive correlation
with serum creatinine on days 1 and 3 (p=0.037
and p=0.015, respectively) and also with CRP, but
only on day 3 (r=0.496, p=0.016).
CONCLUSIONS
NON-SURVIVORS
All routine biochemical parameters as CRP,
creatinine, were determined with standard clinicalchemistry methods recommended by the
International Federation of Clinical Chemistry
(IFCC).
PCT
were
measured
by
enzyme-linked
immunosorbent assays (Vidas Brahms).
sRAGE levels were measured by enzyme-linked
immunosorbent assay (Quantikine, R&D Systems).
Statistical analyses were performed nonparametrically with the Mann-Whitney U test and
Spearman rank correlation analysis, whereas pvalue less than 0.05 was considered to identify a
significant difference. A follow-up at 28 d was
performed to distinguish between survivors and
nonsurvivors.
The results from this study indicate that
increased plasma sRAGE is associated with
adverse
outcomes
in
patients
with
SIRS/sepsis, and could serve as an additonal
independent predictor of the 28-day mortality.
ACKNOWLEDGEMENT
This project was supported by the research project
No MZOVFN2005 of the Czech Ministry of Health.