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Falla Renal en UCI Chest-2012
Falla Renal en UCI Chest-2012
Chest 2012;141;1584-1594
DOI 10.1378/chest.11-1513
The online version of this article, along with updated information and
services can be found online on the World Wide Web at:
http://chestjournal.chestpubs.org/content/141/6/1584.full.html
Identifying patients with impaired renal function is crucial in the setting of critical illness.
Serum creatinine serves as the gold standard for assessing steady-state renal function,
helping to define those with chronic kidney disease (CKD). Although these baseline creati-
nine values are often not available in the setting of critical illness, CKD, whether defined
by serum creatinine or proteinuria, increases the risk of developing acute kidney injury
(AKI). Despite delays in elevations following renal insults, serum creatinine remains the
standard for assessing acute changes in renal function. Standardized definitions of AKI,
using changes in serum creatinine and urine output, have informed the epidemiology of
ICU-acquired AKI and have helped define the long-term outcomes in patients who experience
AKI. A complex cyclical interplay exists between AKI and CKD, in which CKD predisposes
patients to an increased risk of AKI, whereas those with AKI, regardless of baseline renal
function, are more likely to suffer from post-AKI CKD. The clarification of the AKI-CKD
dynamic remains a work in progress and will be aided by the implementation of novel mea-
sures of renal function. Several novel biomarkers of renal function have been proposed to
augment serum creatinine in the diagnosis of AKI and CKD. These biomarkers, taken with
recent clinical investigations, have laid the groundwork for the impending paradigm shift in
risk stratifying and in diagnosing changes in renal function in the ICU.
CHEST 2012; 141(6):1584–1594
Abbreviations: AKI 5 acute kidney injury; AKIN 5 Acute Kidney Injury Network; ATN 5 acute tubular necrosis;
CKD 5 chronic kidney disease; CVD 5 cardiovascular disease; eGFR 5 estimated glomerular filtration rate; ESRD 5 end-
stage renal disease; GFR 5 glomerular filtration rate; MDRD 5 Modification of Diet in Renal Disease; NGAL 5 neutrophil
gelatinase-associated lipocalin; RIFLE 5 risk, injury, failure, loss, and end-stage renal disease; RRT 5 renal replacement
therapy; SCyC 5 serum cystatin C
pitfalls of diagnosing AKI via serum creatinine. The In two recent large randomized trials of RRT dose
latter two stages of AKIN are similar to RIFLE, whereas (ATN trial [N 5 1,124] and RENAL study [N 5 1,465]),
AKIN stage 1 accounts for the absolute change in the in-hospital mortality rates were 49.6% and 44.3%,
serum creatinine. This departure from RIFLE is based respectively.38,41 These data are limited in that RRT is
on the evidence that small changes in serum creatinine often reserved for the most severely ill patients and
over discrete time periods (, 48 h) are associated that the initiation RRT, which automatically constitutes
with adverse patient outcomes in a variety of settings AKIN stage 3, is highly variable across physicians.
of critical illness.39,47,48 In the setting of CKD, the traditional teaching had
Both of these AKI classification schemas have been always been to initiate RRT when the GFR reached
shown to be associated with length of ICU and hos- 10-15 mL/min because this is when patients began to
pital stay, as well as mortality.49-51 However, the use of experience complications related to abnormal elec-
AKIN and RIFLE as diagnostic tools remain limited trolytes, acidosis, uremia, and fluid overload (CKD
given their reliance on serum creatinine and the stage V, Table 1). However, a recent randomized
absence of effective therapeutic interventions for the controlled trial demonstrated that the proactive initia-
treatment of AKI. Creatinine kinetics are such that tion of RRT at higher eGFRs (10-14 mL/min) pro-
serum creatinine often does not increase until 24 or vided no benefit in terms of long-term mortality or other
48 h after a renal injury; thus, by the time a patient adverse patient outcomes compared with waiting for
reaches AKIN stage 1 or RIFLE “risk,” the “window” a definitive indication at lower GFRs, (5-7 mL/min).54
for a potential therapeutic intervention may be closed
(Fig 1). Future iterations of AKI diagnostic schema
will include biomarkers of renal tubular injury/AKI
(discussed later), which increase within minutes to
hours of renal injury, thus obviating the need to rely
on creatinine, an imperfect, time-delayed marker of
filtration.
Regardless of these limitations, the current diagnos-
tic criteria have informed and advanced the epide-
miology of AKI and permit consistent AKI definitions
in clinical investigations. Studies that have specifically
compared RIFLE and AKIN have demonstrated that
neither criteria offer a clear advantage and both remain
hindered by the need to establish a “baseline,” which
is often impossible in the ICU.52
These criteria have furthered our understanding of
the link between AKI and mortality.39 In 71,486 vet-
erans with AKI (22% of a large ICU cohort), after
Figure 1. AKI timing and changes in creatinine/glomerular filtra-
adjusting for severity of illness, the odds of death tion. The figure demonstrates the timing among severe renal
were 2.2 (95% CI, 2.17-2.3) for AKIN stage 1, 6.1 injury, the drop in glomerular filtration rate, and the time-delayed
(95% CI, 5.74-6.44) for stage 2, and 8.6 (95% CI, rise in serum creatinine and other traditional markers of renal
function. Several novel biomarker are able to forecast AKI
8.07-9.15) for stage 3.53 The recent focus on small prior to changes in traditional markers (creatinine and urine out-
changes in serum creatinine (AKIN stage 1 or RIFLE put). This early diagnosis could potentially provide a window to
“risk”) impacting adverse patient outcomes should treat/intervene with RRT or other novel therapeutics and possibly
improve outcomes in the setting of AKI. AKI 5 acute kidney
not take away from the extremely high mortality rate injury; eGFR 5 estimated glomerular filtration rate; RRT 5 renal
in patients with AKI requiring RRT.48 replacement therapy.
AKI/RRT events. Additionally, there is an inherent that designated subjects as NGAL(1) or NGAL(2)
bias in this table because negative studies often go and creatinine(1) or creatinine(2) (AKI was defined
unpublished. Finally, Table 5 makes no attempt to as RIFLE “risk”), individuals who were NGAL(1)
quantify the results of these investigations. but creatinine(2) needed more RRT (OR, 16.4;
It is our opinion that no single biomarker will be 95% CI, 3.6-76.9; P , .001) compared with those
able to predict early AKI (prior to changes in serum who were NGAL(2) and creatinine(2).98 There was
creatinine) as well as AKI severity and duration in all a stepwise increase in ICU stay, hospital stay, and
clinical settings. The pathophysiology of ischemia- mortality across the four study groups:
reperfusion-AKI is different from that of sepsis-AKI,
which is different from radiocontrast nephropathy. NGAL(2)creat (2) , NGAL(1)creat(2) , NGAL
As such, each of these clinical entities may be best (2)creat (1) , NGAL(1)creat(1)
detected by a different set of biomarkers at different
clinical time points. This ability to detect adverse patient outcomes in
Increasingly, biomarkers are being investigated for the absence of significant changes in creatinine is a
their ability to complement, rather than replace, cre- paradigm shift for physicians and will certainly need
atinine. In a pooled prospective study (n 5 2,322) to be validated in follow-up studies.