Acute kidney injury (AKI) is a pathological phenomenon that has changed in name and definition in recent years. The initial concepts of acute kidney failure and renal impairment were difficult to compare between studies, so there was a need to standardize a definition of what can be described as an “acute decline of kidney function as a consequence of a pathological insult”.

In 2004, the Acute Dialysis Quality Initiative group proposed the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) classification for acute renal failure,1 which included serum creatinine (SCr) and/or urine output criteria to define three levels of renal dysfunction and two clinical outcomes.

In 2007, the Acute Kidney Injury Network group proposed the term ‘acute kidney injury’ and a new definition for the entire spectrum of acute renal failure, based on the previous RIFLE criteria.2 It included three stages of AKI, also taking into account SCr and/or urine output.

The latest definition was published in 2012 by the Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group.3 It combines the previous definitions: AKI is present if SCr increases by ≥0.3 mg/dl (≥26.5 μmol/l) in 48 hours or by ≥1.5 times baseline within seven days, or if urine volume is <0.5 ml/kg per hour for six hours.

These criteria were largely derived from critically ill patients in intensive care units, with AKI of varying etiologies, and KDIGO appears to be a better predictor of in-hospital mortality than RIFLE.4 Understanding of AKI in acute coronary syndrome (ACS) is improving, but is still limited. This study aimed to determine the incidence of AKI in ACS patients, to assess its impact on clinical outcomes, and to determine its predictors.

The major findings of this study are that AKI is an independent predictor of major bleeding and mortality (both in-hospital and at one year) and that it is independently associated with easily identifiable clinical variables, such as Killip class >1 at admission, previous renal dysfunction, older age and depressed LVEF. AKI patients tend to be older and more often hypertensive and diabetic, conditions known to affect renal functional reserve, and also tend to have more complex coronary artery disease.

STEMI patients seem to be at greatest risk for developing AKI. This finding is to be expected, since they represent patients with ACS of greatest hemodynamic impact and/or with lowest hemodynamic and renal functional reserve. Interestingly, diuretic use was also an independent predictor of AKI, but only in Killip class 1 patients, not in Killip class >1, which may be a reflection of its benefit only in the presence of marked fluid overload. Statins did not seem to protect against AKI, although these drugs at high doses have been shown to have an important role in preventing AKI.6–8 ACEIs/ARBs also failed to demonstrate a significant protective effect.

Also of note, the performance of angiography and angioplasty were not associated with increased development of AKI, despite the associated use of nephrotoxic contrast agents. In this context, it could be postulated that the hemodynamic benefit of revascularization may outweigh the deleterious effect of contrast use. Increasingly used prophylactic measures for AKI, such as vigorous hydration and high-dose statins, may also have played a part in these results.

Our findings are generally in line with those of previously published studies in several respects. The negative impact of AKI on short- and long-term outcomes of patients undergoing PCI has been demonstrated by several groups, particularly in terms of in-hospital and long-term mortality.9–14 Similarly, in ACS patients development of AKI and its severity are associated with a progressively higher risk of in-hospital morbidity and mortality.15 The commonly used scores for AKI diagnosis and staging have also been tested in ACS, and the KDIGO criteria appear to be better than RIFLE for predicting early and late mortality in myocardial infarction (MI).16

In the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) registry,17 in which most patients had ACS (72%), both cardiovascular and renal events also increased with the presence and severity of AKI. AKI in the setting of ACS is frequently interpreted as contrast-induced, and in this context it has been shown to be a predictor of mortality in-hospital and in follow-up (median 94 months).13

The importance of contrast for the development of AKI in ACS is still the subject of debate. Other mechanisms, with both prerenal and renal pathophysiology, have been proposed, such as the hemodynamic impact of the ACS, bleeding complications, atheroembolic phenomena, drug toxicity and acute hyperglycemia.18 BNP levels have been shown to be associated with the development of AKI, possibly reflecting both cardiac and renal impairment in the context of ACS.19 Radial access has recently been shown in a meta-analysis20 to be significantly less associated with AKI than femoral access, possibly related to reduced bleeding complications. The AKI-MATRIX sub-study21 will probably add important information in this regard. Several groups have recently developed scores to predict the development of AKI after PCI.22–24 Interestingly, they are very robust, despite being based on preprocedural data only, and in all of them AKI appears to be more frequent in ACS, including MI, than in stable patients. This suggests there are important mechanisms of AKI in ACS patients, other than contrast use or volume. In this regard, a recent study by McDonald et al. suggests that iodinated contrast use is not associated with development of AKI in patients undergoing CT.25

Although it is probably not the main mechanism, there is still evidence of the deleterious effect of contrast material on renal function in ACS.26 An early invasive strategy in NSTEMI has been reported to be associated with a small increase in AKI, but not dialysis or progression to end-stage kidney disease, and it still reduced long-term mortality.27 In primary PCI, contrast volume is still an important determinant of AKI,28 regardless of preprocedural risk,29 which supports the idea of keeping contrast use to a reasonable minimum.30

AKI is an important finding in the ACS context, with impact on hard clinical endpoints, such as major bleeding and mortality. Easily identifiable markers of vulnerable patients are Killip class >1 at admission, previous renal dysfunction, older age and depressed LVEF. Care should be taken when using diuretics, which may be deleterious in the absence of fluid overload. Mechanisms other than contrast toxicity are likely to have an important role. Invasive management of ACS does not seem to increase AKI. However, keeping contrast volume to a reasonable minimum is still advisable.

The authors have no conflicts of interest to declare.