Objective
:
To characterize the temporal pattern of a panel of
blood and urinary
acu
te kidney
injury (AKI)
biomarkers in a
n
animal model of
fecal peritonitis
and recovery
Design
: Prospective observational animal study
Setting
: University research laboratory
Subjects
: Male Wistar rats
Interventions
:
A
fluid
-
resuscitated, long
-
term (3 day)
rat model of sepsis (fecal peritonitis)
and recovery
was used
to understand the
temporal association of
AKI
biomarkers
in relation
to systemic hemodynamics, inflammation, and
renal function
.
At pre
-
defined time points (3, 6,
12, 24, 48, 72h), animals (≥6
per group) underwent echocardiography, blood
and urine
sampling, and
had
kidneys taken for histological analysis. Comparison was made against
sham
-
operated controls and naïve animals
.
Measurements and main results
:
The
systemic
pro
-
inflammatory response wa
s maximal at
6 hours,
corresponding with
the
nadir
of stroke volume. Serum creatinine peaked late (24h),
when
clinical
recovery was imminent. Histological evidence of tubular injury and cell death
was minimal
. After a recovery period, all biomarkers return
ed to levels approaching those
observed in sham animals. Apart from urine clusterin and IL
-
18, all other urin
ary
biomarkers
were elevated at earlier time
-
point
s compared
to serum creatinine. Urine NGAL was the most
sensitive marker among those studied, ris
ing from 3h. While serum creatinine fell at 12h,
serum cystatin C increased, suggestive of decreased creatinine production.
Conclusions
:
Novel information is reported on the temporal profile of a panel of renal
biomarkers in sepsis in the context of system
ic and renal inflammation and recovery.
I
n
sight
into the pathophysiology of AKI is gleaned from the temporal change
m
arkers of
renal
injury
(urine NGAL, KIM
-
1,
c
albindin)
,
followed by
a
marker of cell cycle arrest (urine IGFBP7) and
,
finally
,
by functional
markers of filtration (serum creatinine and cy
s
tatin C).
These clinically
relevant findings
should have significant influence on
future clinical testing.