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Heart Online First, published on August 4, 2015 as 10.1136/heartjnl-2015-307773
Centro Cardiologico Monzino,
I.R.C.C.S., University of Milan,
Milan, Italy
Correspondence to
Dr Giancarlo Marenzi, Centro
Cardiologico Monzino, Via
Parea 4, Milan 20138, Italy;
giancarlo.marenzi@ccfm.it
Received 5 March 2015
Revised 22 May 2015
Accepted 15 July 2015
To cite: Marenzi G,
Cosentino N, Bartorelli AL.
Heart Published Online First:
[please include Day Month
Year] doi:10.1136/heartjnl-
2015-307773
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd (& BCS) under licence.
Acute kidney injury in patients with acute coronary
syndromes
Giancarlo Marenzi, Nicola Cosentino, Antonio L Bartorelli
ABSTRACT
Acute kidney injury (AKI) is increasingly being seen in
patients with acute coronary syndromes (ACSs). This
condition has a complex pathogenesis, an incidence
that can reach 30% and it is associated with higher
short-term and long-term morbidity and mortality.
Nevertheless, AKI is still characterised by lack of a
single accepted definition, unclear pathophysiology
understanding and insensitive diagnostic tools that make
its detection difficult, particularly in the setting of ACS.
Recent data suggested that patients with AKI during
ACS, even those in whom renal function seems to fully
recover, face an increased, persisting risk of future AKI
and may develop chronic kidney disease. Thus, in these
patients, nephrology follow-up, after hospital discharge,
and secondary preventive measures should possibly be
implemented. In this review, we aim at providing a
framework of knowledge to increase cardiologists’
awareness of AKI, with the goal of improving the
outcome of patients with ACS.
INTRODUCTION
Acute kidney injury (AKI) is a complex disorder
characterised by early (within hours or days) wor-
sening of renal function, with clinical manifesta-
tions ranging from minimal increase in serum
creatinine (sCr) to anuric renal failure requiring
renal replacement therapy.1
There has been accumulating evidence of the
association between AKI and acute coronary syn-
drome (ACS); however, several important issues are
still poorly defined. First, AKI detection may be
often missed and its relevance underestimated by
cardiologists. Physicians tend to disregard mild or
transient sCr elevation during hospital stay for ACS,
especially when sCr level remains within the normal
range or decreases rapidly, and they often attribute
small sCr increases to laboratory variations.
However, the coefficient of sCr variation with
modern analysers is relatively small. Therefore, it is
highly unlikely that increments of 0.3 mg/dL are
due to assay inaccuracy.2 Second, in most studies,
AKI has been identified as a dichotomous event that
may occur during hospitalisation.3 In fact, sCr
increase in ACS is often a reversible phenomenon
with values that may rapidly return to normal, or
may be partially or completely irreversible, leading
to progressive chronic kidney disease (CKD). It is
somewhat surprising that most influential cardiology
textbooks and recent guidelines did not draw much
attention, if any, on AKI in patients with ACS.
Indeed, while recommendations exist for the man-
agement of potential, but fairly rare ACS-associated
complications, such as papillary muscle rupture or
Dressler pericarditis, both occurring in <2% of
Marenzi G, et al. Heart 2015;0:1–8. doi:10.1136/heartjnl-2015-307773
Review
patients, no information is given about AKI, despite
its incidence may be as high as 30%.4 5 The lack of a
common reference point on AKI created confusion
and made comparisons difficult among studies
investigating preventive and therapeutic approaches,
which, however, are beyond the object of the
present review. Indeed, we here aim at providing a
framework of knowledge to raise awareness of AKI
in the cardiology community, with the goal to ultim-
ately improve outcomes of patients with ACS devel-
oping AKI.
PATHOPHYSIOLOGY OF AKI
AKI in ACS is a multifactorial phenomenon that
could be promoted by underlying renal dysfunction,
but it is more often influenced by multiple contrib-
uting factors (figure 1).6 7 Beyond the widely recog-
nised negative impact of contrast volume,7–9 the key
mechanisms in AKI pathogenesis include systemic
and renal haemodynamic changes secondary to
impaired cardiac output (‘arterial underfilling’) and
increased venous congestion (‘venous overfilling’)
that lead to decreased glomerular filtration rate
(GFR). Moreover, an imbalance of endogenous
vasodilating and vasoconstrictive factors appears to
be involved, as patients with ACS are characterised
by a progressive activation of several neurohormo-
nal systems that exert profound effects on kidney
perfusion and function.10 11 Changes in volume
status, drugs, atheroembolism during percutaneous
coronary intervention (PCI) or intra-aortic balloon
pump counterpulsation and bleeding are common
conditions in patients with ACS, which may contrib-
ute to the development of AKI. Moreover,
intra-aortic balloon pump, used in cases of cardio-
genic shock and reduced systemic perfusion, may
itself also impair renal perfusion, when not properly
positioned. A burst of immunological and inflamma-
tory activation has also been advocated among the
potential causes of further renal injury.10 11 Indeed,
enhanced inflammatory response, increased oxida-
tive stress and sympathetic activation have been
shown to synergistically accelerate AKI in patients
with ST-segment elevation myocardial infarction
(STEMI).12 Finally, metabolic factors, including
acidosis and acute hyperglycaemia, may be impli-
cated in AKI development.13
Taken together, these considerations may explain
why patients with ACS are at risk of AKI if they
have pre-existing CKD and when their renal func-
tion is normal,14 15 and if they receive medical
therapy only,5 further supporting the notion that
the term ‘AKI’, rather than ‘contrast-induced
nephropathy’ or ‘contrast-induced AKI’, is more
appropriate to depict acute renal impairment
during ACS.
1
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Figure 1 Mechanisms possibly involved in the pathophysiology of AKI in patients with acute coronary syndrome (ACS). ACE-inhibitors, ACE
inhibitor; ACS, acute coronary syndrome; AKI, acute kidney injury; ARBs, angiotensin receptor blockers; CKD, chronic kidney disease; IABP,
intra-aortic balloon pump; PCI, percutaneous coronary intervention; NSAID, non-steroidal anti-inflammatory drugs.

DEFINITIONS OF AKI In order to overcome the shortcomings of AKI heterogeneous

The choice of a shared definition for AKI, independently of its
underlying mechanisms, has critical consequences, as it determines
our estimates of incidence, outcomes and costs, it influences the
timing of consultation to nephrologist and it shapes the way pre-
vention, interventional and follow-up care studies are performed.
Unfortunately, more than 30 AKI definitions currently exist, and
this heterogeneity can be found also in the setting of ACS, creating
difficulties in comparing study results.16–21
Current myocardial revascularisation guidelines define
contrast-induced nephropathy, the renal complication cardiolo-
gists are mostly acquainted with, as an absolute increase in sCr
≥0.5 mg/dL or a relative increase in sCr ≥25% above the base-
line value within 48–72 h of contrast administration. However,
because of the curvilinear relationship between sCr and GFR,
patients with different levels of renal function at baseline who
have a similar increase in sCr values exhibit a different GFR
decrease (figure 2A).22 Indeed, for increasing baseline sCr
values, the absolute change in GFR is progressively less.
Therefore, small sCr changes are associated with greater GFR
reduction at lower sCr as compared with higher sCr levels; on
the other hand, in patients with elevated sCr, small GFR
changes produce dramatic sCr changes. Conversely, when rela-
tive (%) instead of absolute sCr changes are considered, similar
reductions in GFR are expected regardless of sCr baseline value
(figure 2B). Thus, the sole definition that may more closely
establish prognosis in patients with ACS remains unclear and
should be investigated in large prospective studies.
definitions, three consecutive classifications were developed
(table 1).23–25
In 2005, Chertow26 published a seminal study demonstrating
that a sCr increase as small as 0.3 mg/dL is highly associated
with patients’ outcomes. Therefore, to take into account the
clinical significance of even relatively small sCr increases, the
Risk, Injury, Failure, Loss and End-stage renal disease (ESRD)
(RIFLE) criteria were refined by the Acute Kidney Injury
Network (AKIN).24 This standardised definition of AKI has
been embraced by the nephrology and critical care communities
over the past 5 years and it is now the predominant classification
employed also by cardiologists.4 18 27 The third and more
recent classification was developed in 2012 by the Kidney
Disease: Improving Global Outcomes (KDIGO) AKI Work
Group.25 To date, no definite data comparing the incidence and
the outcomes of AKI, defined by RIFLE and AKIN criteria, are
available in ACS. Only a single study has recently compared
RIFLE and KDIGO criteria for AKI assessment in 1050 patients
with acute myocardial infarction (AMI).28 Of note, KDIGO cri-
teria detected substantially more patients with AKI than RIFLE
(37% vs 15%, respectively) as a result of a higher stage 1 AKI
incidence (31% vs 10%, respectively). Importantly, patients in
whom AKI was diagnosed with KDIGO criteria but was missed
using RIFLE definition had a significantly longer hospital stay
and higher 30-day and 1-year mortality rates, suggesting that
KDIGO criteria are more appropriate for AKI diagnosis than
RIFLE criteria in patients with ACS.

2 Marenzi G, et al. Heart 2015;0:1–8. doi:10.1136/heartjnl-2015-307773

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Figure 2 (A) Relationship between

serum creatinine (sCr) and glomerular
filtration rate (GFR). Due to a
curvilinear correlation, GFR reduction
differs according to initial sCr value. For
instance, a similar increase in sCr from
point A to B corresponds to a ∼50%
GFR reduction in patient 1 and ∼10%
in patient 2. (B) GFR changes (Δ%)
according to absolute (>0.5 mg/dL) or
relative (>25%) increase in sCr.

In patients with ACS, sCr measurement at hospital admission
is usually used as the reference value to diagnose AKI; however,
this value may be affected by the ongoing disease process
started before hospitalisation. As a result, some patients who
already developed AKI before hospital admission may be mis-
classified as ‘no-AKI’ subjects only because their sCr does not
increase further or, even, show an apparent improvement.29
Finally, when GFR acutely decreases, sCr rises slowly, usually
within days, or may not even change until about 50% of kidney
function has decreased. Thus, sCr concentration is a delayed,
unreliable measure of kidney dysfunction in the acute setting.30
Accordingly, although AKI occurs in the very early phase of
ACS, it is usually recognised later.16 Thus, validation of new
early markers of AKI might allow to identify patients at risk in a

Table 1 RIFLE, AKIN and KDIGO classification schemes for AKI

sCr and /or GFR criteria UO criteria

RIFLE
An acute ↑ in sCr or ↓ in GFR over 7 days UO <0.5 mL/kg/h×6 h
Risk ↑ in sCr ≥1.5×baseline or ↓ in GFR >25% UO <0.5 mL/kg/h×12 h
Injury ↑ in sCr ≥2.0×baseline or ↓ in GFR >50% UO <0.3 mL/kg/h×24 h or anuria× 12 h
Failure ↑ in sCr ≥3.0×baseline or
↑ in sCr ≥0.5 mg/dL if baseline sCr ≥4.0 mg/dL or
↓ in GFR >75%
Loss Complete loss of kidney function >4 weeks
ESRD End-stage renal disease >3 months
AKIN
An acute ↑ in sCr or ↓ in GFR within 48 h
Stage 1 ↑ in sCr ≥1.5–2.0×baseline or ↑ in sCr ≥0.3 mg/dL UO <0.5 mL/kg/h×6 h
Stage 2 ↑ in sCr >2.0–3.0×baseline or ↓ in GFR ≥50% UO <0.5 mL/kg/h×12 h
Stage 3 ↑ in sCr >3.0×baseline or UO <0.3 mL/kg/h×24 h or anuria×12 h
sCr ≥4.0 mg/dL with an acute ↑ ≥0.5 mg/dL or
initiation of RRT
KDIGO
An acute ↑ in sCr within 48 h or ↓ in GFR over 7 days
Stage 1 ↑ in sCr ≥1.5–1.9×baseline or ↑ in sCr ≥0.3 mg/dL UO <0.5 mL/kg/h×6 h
Stage 2 ↑ in sCr ≥2.0–2.9×baseline UO <0.5 mL/kg/h× 12 h
Stage 3 ↑ in sCr ≥3.0×baseline or sCr ≥4.0 mg/dL with an acute ↑ ≥0.5 mg/dL or UO <0.3 mL/kg/h×24 h or anuria×12 h
initiation of RRT
↑, increase; ↓, decrease; AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; ESRD, end-stage renal disease; GFR, glomerular filtration rate; KDIGO, Kidney Disease: Improving
Global Outcomes; RIFLE, Risk, Injury, Failure, Loss and End-stage renal disease; RRT, renal replacement therapy; sCr, serum creatinine; UO, urine output.

Marenzi G, et al. Heart 2015;0:1–8. doi:10.1136/heartjnl-2015-307773 3

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Figure 3 Incidence of acute kidney

injury according to its definition in
different subsets of patients with ACS
(the definitions of ACS refer to those
used in the referenced studies). ACS,
acute coronary syndrome; NSTEMI,
non-ST-segment elevation myocardial
infarction; sCr, serum creatinine;
STEMI, ST-segment elevation
myocardial infarction; RIFLE, Risk,
Injury, Failure, Loss and End-stage
renal disease.

very early phase, allowing preventive treatments which may
help to minimise further injury.30
INCIDENCE OF AKI
The reported incidence of ACS-associated AKI is extremely het-
erogeneous, ranging from 5% to 55%, and it varies with the cri-
teria used for diagnosing AKI, the clinical setting and the
investigated population (figure 3).4 5 16–18 31–34 Recent data
from the Acute Coronary Treatment and Intervention Outcomes
Network (ACTION) registry demonstrated that AKI occurred in
16% of 59 970 patients with AMI (6.5% with mild AKI, 5.6%
with moderate AKI and 4% with severe AKI).21 The rate of
AKI, defined according to the RIFLE criteria, also occurred in
15% of patients with AMI,34 (9% in the risk category, 4.5% in
the injury category and 1% in the failure category). When
AKIN criteria were used, AKI occurred in 13% of patients with
ACS (64% with stage 1, 6% with stage 2 and 30% with
stage 3).27 These data were recently confirmed in the large-scale
Harmonizing Outcomes With Revascularization and Stents in
Acute Myocardial Infarction (HORIZONS-AMI) trial, which
reported AKI in 16% of the patients.8 However, it is note-
worthy that the true incidence of AKI was underestimated in all
these studies due to the exclusion of patients who died early,
thus not allowing at least two consecutive daily sCr values to be
collected.21 27 35
PROGNOSTIC RELEVANCE OF AKI
Short-term prognosis
A growing amount of data now exists on the association
between AKI and in-hospital outcomes (table 2).
A significant progressive increase in in-hospital mortality was
observed in patients with ACS between those without AKI and
those with stage 1, stage 2 and stage 3 AKI (1% vs 9.5% vs
43%).27 Similar findings were observed in another cohort of
patients with ACS, where in-hospital mortality of patients with
AKI was 18 times greater than that of patients without AKI.36
An in-hospital mortality of 31% and of 0.6% was found in
4 Marenzi G, et al. Heart 2015;0:1–8. doi:10.1136/heartjnl-2015-307773
patient with STEMI with and without AKI after primary PCI.14
In very high risk settings, such as in STEMI complicated by car-
diogenic shock, AKI was found to be the strongest independent
predictor of in-hospital mortality.16 In 2012, Fox et al21 showed
that the in-hospital mortality rate in patients with mild (0.3 to
<0.5 mg/dL), moderate (0.5 to <1.0 mg/dL) or severe
(≥1.0 mg/dL) AKI was 7%, 14% and 32%, respectively, com-
pared with 2% in those without AKI. These authors observed a
graded mortality risk by AKI category even among those with
sCr changes as low as 0.1 mg/dL, highlighting that even trivial
sCr increases deserve attention.
Long-term prognosis
The literature examining the association between AKI and long-
term mortality is growing and supported by increasingly robust
data (table 2).
Hwang et al35 demonstrated that 1-year mortality in 2053
patients with AMI increased according to the severity of AKI:
81% of patients who had stage 3 AKI were dead at 1-year com-
pared with 40%, 25%, 4% of patients with stage 2, stage 1 and
no AKI, respectively. When clinical analysis was extended to
longer-term follow-up, data still showed such detrimental associ-
ation between AKI and worse prognosis in patients with ACS.
Amin et al17 observed that AKI, at a threshold of 0.3 mg/dL
increase of sCr, was independently associated with mortality at
4 years. Importantly, the interaction between AKI and baseline
sCr was not significant, confirming that an absolute increase of
>0.3 mg/dL in sCr conferred a similar mortality risk in patients
with normal or impaired renal function at baseline. These data
were recently confirmed among patients with STEMI, in whom
a ≥0.3 mg/dL elevation in sCr was associated with a marked
increase in all-cause mortality up to 5 years.32 Finally, the work
by Narula et al8 is a further and recent piece of evidence of
how AKI can affect long-term prognosis in patients with STEMI
undergoing primary PCI. At 3-year follow-up, they found that
patients with AKI had a 16% mortality rate as compared with
4% in patients with non-AKI. When the combination of major
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Table 2 Adverse prognosis associated with AKI in most recent observational clinical studies investigating ACS populations
Study Study Patients AKI definition
Authors (year) design population (n) (sCr increase) End point associated with AKI

Marenzi et al (2004) 14
Prospective STEMI 208 >0.5 mg/dL ↑ in-hospital mortality
↑ in-hospital clinical complications
Goldberg et al (2005)5 Prospective STEMI 1038 ≥0.5 mg/dL ↑ in-hospital mortality
↑ 1-year mortality
Parikh et al (2008)4 Retrospective AMI 147 007 ≥0.3 mg/dL ↑ 10-year mortality
Goldberg et al (2009)20 Retrospective STEMI 1957 ≥0.3 mg/dL ↑ 3-year mortality
↑ 3-year admission for heart failure
Marenzi et al (2009)7 Prospective STEMI 561 >25% ↑ in-hospital mortality
↑ in-hospital clinical complications
Amin et al (2010)17 Prospective STEMI and NSTEMI 393 ≥0.3 mg/dL ↑ 4-year mortality
Anzai et al (2010)12 Prospective STEMI 141 ≥0.3 mg/dL ↑ in-hospital MACE
↑ 3-year MACE
Marenzi et al (2010)13 Prospective STEMI 780 ≥25% ↑ in-hospital mortality
Marenzi et al (2010)16 Prospective STEMI with CS 97 ≥25% ↑ in-hospital mortality
↑ in-hospital clinical complications
Senoo et al (2010)33 Prospective ACS 338 >0.5 mg/dL or >25% ↑ in-hospital mortality
Hwang et al (2011)35 Retrospective STEMI and NSTEMI 2053 AKIN ↑ 1-year mortality
Wi et al (2011)9 Retrospective STEMI and NSTEMI 1041 >0.5 mg/dL or >25% ↑ in-hospital mortality
↑ 2-year cumulative event of death or HD
Bruetto et al (2012)34 Prospective STEMI and NSTEMI 828 RIFLE ↑ 30-day mortality
↑ 1-year mortality
Fox et al (2012)21 Retrospective STEMI and NSTEMI 59 970 ≥0.3 mg/dL ↑ in-hospital mortality
↑ in-hospital major bleeding
Kume et al (2013)31 Retrospective STEMI 194 >0.5 mg/dL or >50% ↑ 3-year mortality
Marenzi et al (2013)27 Retrospective ACS 3210 AKIN ↑ in-hospital mortality
↑ in-hospital clinical complications
Rodrigues et al (2013)28 Prospective STEMI and NSTEMI 1015 RIFLE and ↑ 30-day mortality
KDIGO ↑ 1-year mortality
Shacham et al (2014)32 Retrospective STEMI 1033 AKIN ↑ 30-day mortality
↑ 5-year mortality
ACS, acute coronary syndromes; AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; AMI, acute myocardial infarction; CS, cardiogenic shock; HD, haemodialysis; KDIGO,
Kidney Disease: Improving Global Outcomes; MACE, major adverse cardiac events; NSTEMI, non-ST-elevation myocardial infarction; RIFLE, Risk, Injury, Failure, Loss and End-stage renal
disease; sCr, serum creatinine; STEMI, ST-elevation acute myocardial infarction.

bleeding and ischaemic major adverse cardiac events at 3 years
was considered, the adverse event increase was even more
impressive, reaching 40% in patients with AKI and averaging
25% in patients with non-AKI.8 Taken together, these data high-
light that AKI development heavily affects overall prognosis of
patients with ACS.
Transient versus sustained AKI
The course of sCr values must be closely followed during ACS
hospitalisation as AKI occurrence, severity and its behaviour
over time (transient vs persistent) may have significant clinical
implications.
The first evidence comes from the study of Latchamsetty
et al,37 who showed that a transient increase in sCr >0.5 mg/dL
in patients with ACS is independently associated with a twofold
increase in 6-month mortality. Goldberg et al20 found in
patients with STEMI that the rate of transient AKI was about
40% in all AKI cases, and they observed at 36-month follow-up
that patients with persistent moderate/severe AKI had the
highest mortality, whereas patients with transient moderate/
severe injury had an intermediate risk. Similarly, in the study by
Wi et al,9 persistent renal dysfunction within 1 month of AMI
hospitalisation, was associated with higher 2-year death or dialy-
sis rates than those with transient AKI. Similarly, among 1490
patients with an estimated creatinine clearance <60 mL/min
who underwent coronary angiography, transient and persistent
Marenzi G, et al. Heart 2015;0:1–8. doi:10.1136/heartjnl-2015-307773
renal damage were both independent predictors of long-term
clinical outcomes, increasing 1.6-fold and 2.5-fold, respectively,
the risk of mortality, dialysis or major cardiovascular events at
5-year follow-up.38
RENAL IMPLICATIONS OF AKI
Although incomplete recovery from severe AKI is a well-
recognised pathway to persistent and progressive CKD, recent
data indicate that AKI, also when characterised by a transient and
mild kidney dysfunction, more than likely results in persistent
loss of kidney function, faster subsequent rate of decline in
kidney function and future risk of progression to ESRD.9 19 38–41
Of note, the greater the severity of AKI, the higher the risk of
CKD and ESRD progression.40 41 Moreover, the severity and the
duration of an AKI episode predict progression to CKD, with
persistent AKI being a stronger independent risk factor for late
ESRD.9 19 38 40 Thus, the common opinion on the reversible
nature of renal damage in AKI seems to concern sCr concentra-
tion only.
These speculations are supported by both clinical and experi-
mental observations. Indeed, a recent study demonstrated that a
persistent deterioration of kidney function, defined as a >25%
or >0.5 mg/dL increase in sCr above baseline, was still detect-
able between 6 and 8 months after PCI in about 40% of patients
developing AKI during ACS, and that it was a strong independ-
ent predictor of 5-year mortality.42 The Alberta Provincial
5
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Project for Outcome Assessment in Coronary Heart Disease
(APPROACH) showed that, among 14 782 patients (10 671
with ACS) undergoing coronary angiography, AKI was asso-
ciated with an increased risk of death, progression to ESRD,
and subsequent hospitalisation for AKI, but not of hospitalisa-
tion for AMI and cerebrovascular events, at long-term (median
19.7 months) follow-up.19
These pieces of clinical evidence have also been supported by
experimental data. Early studies demonstrated that renal blood
flow and clearance function may remain impaired for a pro-
longed period of time after AKI, despite sCr normalisation.
More recently, both histological and physiological changes have
been shown to persist after experimental AKI, despite sCr nor-
malisation.43–45 Thus, through inflammatory and fibrotic phe-
nomena, kidney may undergo progressive structural damage,
which may then predispose to a more rapid GFR decrease.
Initially, these changes can be functionally compensated for by
adaptations in renal haemodynamics to maintain sufficient GFR,
resulting in glomerular overfiltration in the residual nephrons
and release of neurohormones that affect renal blood flow.
However, in the setting of impaired renal function, the kidney
may lack sufficient functional reserve and is more likely to
develop irreversible damage. If we transfer these data to the
clinical arena, we can explain why patients with concomitant
AKI and CKD are far more likely to develop ESRD.39 This may
also explain the remarkably higher mortality observed among
patients with ACS impaired GFR at admission who develop
AKI,34 as the combination of an AKI-induced loss of nephrons
in an already failing kidney may ultimately hamper the ability to
compensate for any further injury. On the other hand, in
patients with pre-existing normal function, multiple episodes of
AKI may dissipate renal reserve,46 promoting the development
of CKD, as each additional AKI episode has been associated
with an independent, cumulative increase in the risk of
advanced CKD.47 Thus, AKI may identify subjects who fail
their renal ‘stress test’ due to a limited renal reserve and who
are more likely to have progressive kidney disease. On the evi-
dence of these clinical and experimental data, it is reasonable to
hypothesise that the essential pathophysiology connecting AKI,
CKD and ESRD is indeed the reduction of renal mass (figure 4).
Taking into account these intriguing findings and considering
that no established medical therapies have been proven to affect
short-term prognosis in AKI, secondary preventive measures
aimed at improving outcomes among survivors of AKI are of
paramount importance. Indeed, the majority of patients with
AKI are not being routinely followed by nephrologists, and
follow-up for mild AKI barely exists in the current clinical prac-
tice;48 filling this gap may represent a major opportunity for a
significant improvement in the care of this population. Indeed,
patients who have ACS with AKI are likely to benefit from
closer monitoring of their residual renal function and protection
against additional renal injury. Of note, a recent meta-analysis

Figure 4 Schematic representation of the hypothetical mechanism underlying the progression from normal renal function to chronic kidney disease
in a patient developing kidney injury. The green area indicates the glomerular filtration rate (GFR), while the red area indicates the functional reserve
of the kidney. (A) In a patient with a preserved nephron function, nephrons do not work at their maximal capacity. Thus, a functional renal reserve
is available. (B) After an acute renal insult, normalisation of serum creatinine (sCr) and normal GFR are achieved by compensatory hyperfiltration of
the remaining healthy nephrons. However, a reduction in functional renal reserve occurs. (C) After functional renal reserve exhaustion, any further
loss of healthy nephrons will result in an increase in sCr and in a reduction in GFR.

6 Marenzi G, et al. Heart 2015;0:1–8. doi:10.1136/heartjnl-2015-307773

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has clearly demonstrated that early involvement of a nephrolo-
gist in the care of patients with renal insufficiency improves out-
comes,49 stabilising or slowing the progression of CKD.50
CONCLUSIONS
In summary, AKI is a complex syndrome that is increasingly
recognised as a frequent and potentially catastrophic complica-
tion of ACS. Not only its development but also its severity is
independently associated with increasing morbidity and mortal-
ity, both at short-term and long-term follow-up. Although AKI
is of major clinical relevance, a single accepted definition is still
lacking, determining discordant data on estimates of incidence
and outcomes. Furthermore, it is now evident that survivors,
even those in whom renal function seems to fully recover, face
an increased and persisting risk of renal damage. This may
favour CKD development and may be the reason for the
observed worse outcomes, including the higher mortality risk.
Yet, the majority of patients with AKI do not have any nephrol-
ogy follow-up after hospital discharge. Therefore, an important
research target is the identification of high-risk patients with
ACS experiencing AKI, thereby proper follow-up and secondary
preventive measures may be implemented.
Acknowledgements We acknowledge Michela Palmieri for her precious help in
revising the manuscript.
Contributors All authors have significantly contributed to manuscript
conceivement, preparation and writing.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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8 Marenzi G, et al. Heart 2015;0:1–8. doi:10.1136/heartjnl-2015-307773

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Acute kidney injury in patients with acute

coronary syndromes
Giancarlo Marenzi, Nicola Cosentino and Antonio L Bartorelli

Heart published online August 4, 2015

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