Discussion
The results from our large, multicentre Australian population-based study of patients undergoing PCI showed that NRI occurred in 3.1%, and necessitated dialysis in 0.6% of cases. Comorbid patients were shown to have a higher risk, with diabetes, peripheral vascular disease and cerebrovascular disease each being independently associated with the development of NRI/NDR. In particular, the presence of severe left ventricular dysfunction increased the odds of developing NRI/NDR by more than threefold, and the presence of CKD stages IV–V increasing the odds almost sixfold. As expected, NRI/NDR was more likely to be observed in patients with more acute or complex presentations; with urgent PCI (for an acute coronary syndrome), cardiogenic shock, requirement for adjunctive device and both OHCA and IHCA being powerful predictors of NRI/NDR. From a clinical perspective, these data highlight the presence of readily identifiable risk factors for the development of NRI and NDR, which may be used to enhance decision-making regarding the appropriateness of an invasive approach, timing of procedures and possible targeted prophylactic measures among high-risk patients, which may lower rates of NRI.19
Our data also indicate a clear association between NRI and adverse clinical outcomes, with in-hospital mortality being significantly higher in the NRI (17%) and NDR (45%) groups as compared with those without NRI (1.2%). It is clear that both NRI and NDR also carry a significant morbidity burden, with higher rates of revascularisation (repeat PCI as well as CABG), major bleeding and stroke observed in these patients. The associated increase in morbidity and mortality endpoints persist at 30-day follow-up and are also reflected in subsequent longer-term mortality (Supplementary Figure 3). Similar findings were demonstrated by a pooled analysis from HORIZONS-AMI and ACUITY trial patients conducted by Giacoppo et al, who report markedly increased rates of all-cause mortality and MACE among a similar cohort even at the 1-year mark, with contrast-induced nephropathy being the strongest predictor for death.20 As causality cannot be inferred from our present study, it is likely that a proportion of the observed association between NRI/NDR and poor outcomes is attributable to the more unwell patients within the cohort, such as those requiring urgent PCI and presenting shocked or in cardiac arrest. Nevertheless, the data strongly correlate NRI/NDR with worse outcomes, clearly establishing both NRI and NDR as important clinical markers that herald poor cardiovascular outcomes for patients.
The reported incidence of NRI (3.1%) in our study is largely in keeping with the incidence of renal impairment post-PCI that has been widely documented in the previous literature, with rates cited as low as 0.7% and as high as 17%,2 6 10 19 21 depending on the studied population and definitions of NRI applied. However, a large proportion of these studies have been published over a decade ago, with a distinct lack of population-based contemporary studies. Modern studies looking at the incidence and outcomes of renal impairment can be considered particularly valuable given the recent advances in prophylactic measures aimed at mitigating rates of NRI, with recent Kidney Disease: Improving Global Outcomes international guidelines recommending a careful pre-PCI selection process, judicious use of CM, intravenous volume expansion and low/iso-osmolar media agents.13 Contemporary cardiac guidelines support these sentiments, recommending all patients undergoing angiography to be evaluated for the risk of developing NRI and to use adequate intravenous hydration and high-dose statins to minimise the risk of renal impairment.22
The definition selected for NRI plays an important role in determining the incidence of renal impairment post-PCI. Indeed, a common explanation for the heterogeneity in the reported incidence of renal impairment post-PCI has been the use of various different definitions for renal impairment.20 23 The definition used for inclusion into the NRI group in this study is an absolute increase in SCr of 44.2 µmol/L or relative increase in SCr of 25%. This definition is the most consistently used in the literature and, after comparison with various other definitions, has been shown to consistently predict MACE and mortality after PCI.14–16 A large, contemporary study by Tsai et al concluded the rate of renal impairment post-PCI to be 7.1% among their 985 000 patients, with 0.3% requiring dialysis.24 The reportedly higher incidence of renal impairment may be in part due to their use of the more sensitive definition of acute kidney injury (AKI) adopted by the Acute Kidney Injury Network: a>0.3 mg/dL absolute or >50% relative increase in SCr.25 The utilisation of more sensitive definitions has also been seen in other studies26 and comes with the potential benefit of detecting additional patients at an increased risk of poorer outcomes, but will tend to produce heterogenous groups inclusive of low-risk patients.27 A key strength of our study is therefore our use of a widely accepted definition for renal impairment post-PCI that enables the stratification of only the highest risk patients most susceptible to adverse cardiovascular outcomes.28
Study limitations
There are a number of study limitations to note. The key drawback to this study is its observational nature. Powerful associations were made with morbidity and mortality outcomes; however, we cannot ascertain causality, and it is likely that a number of cardiovascular outcomes such as MI and revascularisation were also contributory to the observed rates of renal impairment, as has been previously described by the cardiorenal relationship.20 22 29 The retrospective nature of the study makes it difficult to ascertain whether the recorded renal impairment was truly due to contrast from the invasive procedure, as VCOR does not collect data to rule out other causes of renal failure. For this reason, the umbrella term NRI was used in preference to contrast-induced nephropathy, acknowledging that many of our patient group may have multifactorial aetiologies of the renal impairment, overestimating the true incidence of contrast-induced nephropathy. Moreover, as this analysis was not prespecified during dataset generation, certain variables previously linked with renal impairment such as the dose of contrast administered and concomitant renotoxic medications17 19 22 were not collected by VCOR, and thus their relationship to NRI/NDR in our population was unable to be examined.