In this cohort study, compared with people managed conservatively, people with otherwise similar characteristics who received early invasive management for non-ST segment elevation acute coronary syndrome were modestly more likely to develop acute kidney injury during admission to hospital. Despite this finding, early invasive management was not associated with a significant increase in short term risk of acute kidney injury requiring dialysis, or long term risk of end stage renal disease, but was associated with better long term survival. Similar findings were observed when people who received invasive procedures at any time during admission to hospital were compared with those managed medically, and when those who received coronary revascularisation were compared with those who received medical management alone. Although patients with lower estimated glomerular filtration rate at admission were less likely to receive invasive management and were at higher risk of adverse outcomes, the associations between invasive management and clinical outcomes remained consistent across varying levels of baseline estimated glomerular filtration rate. These finds suggest that the additional short term risks of acute kidney injury associated with invasive coronary procedures are fairly small and, when considered alongside other clinical outcomes, should not act as a deterrent to their use.
Data on the risk of adverse renal events from randomised trials of early invasive versus conservative treatment for acute coronary syndrome are limited, in part due to the exclusion of patients with moderate to severe renal insufficiency from trials. Among people with baseline serum creatinine concentrations <1.7 mg/dL (150 μmol/L) enrolled in the Fast Revascularization during InStability in Coronay artery disease (FRISC) trial, estimated glomerular filtration rate declined similarly in the early invasive and conservative management arms; however, the incidence of acute kidney injury, acute dialysis, and end stage renal disease was not reported.32
Several previous observational studies have shown a high incidence of acute kidney injury after coronary angiography and percutaneous coronary intervention in people with chronic kidney disease,10
and strong associations between acute kidney injury and death, major adverse cardiovascular events, and kidney failure requiring dialysis in this setting.12
Although other studies have examined the links between acute kidney injury and mortality and end stage renal disease in people admitted to hospital with myocardial infarction treated with either invasive or medical management,18
these studies have not compared renal outcomes on the basis of treatment strategies.
Our findings show that acute kidney injury is a relatively common complication in people with non-ST elevation acute coronary syndrome and chronic kidney disease and increases substantially with lower baseline estimated glomerular filtration rate. However, the difference in the incidence of acute kidney injury between people who receive early invasive management and similar patients treated conservatively is relatively small. Importantly, despite the modestly higher risk of acute kidney injury associated with early invasive management at all levels of estimated glomerular filtration rate, our findings suggest that this strategy is not associated with higher risks of more clinically relevant renal outcomes (including acute dialysis or progression to end stage renal disease), which occurred much less often at all levels of baseline estimated glomerular filtration rate, regardless of treatment strategy. Since early invasive management seemed to be consistently associated with a long term survival advantage at all levels of baseline estimated glomerular filtration rate, these findings (interpreted in light of their consistency with results from randomised trials showing that early invasive management improves long term survival in high risk patients3
) suggest that restricting or delaying access to invasive coronary procedures may not avoid most cases of clinically relevant acute kidney injury and could deny high risk individuals (including those with pre-existing chronic kidney disease) important benefits.
There are several potential mechanisms for the higher risk of acute kidney injury associated with early invasive management. People who received early invasive management were more likely to receive coronary angiography, percutaneous coronary intervention, coronary artery bypass grafting surgery, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers, placing them at risk of acute kidney injury from contrast exposure, perioperative ischaemia, and haemodynamic effects. Furthermore, patients who received invasive management had a longer hospital stay and more measurements of creatinine during follow-up, which may have increased the probability that acute kidney injury would be ascertained. However, the magnitude of the increased risk associated with invasive management strategies was small, suggesting that patients’ characteristics such as age, comorbidity, pre-existing chronic kidney disease, drug use (including diuretics and inhibitors of the renin angiotensin system), and haemodynamic instability are more important contributors to the risk of acute kidney injury in patients with acute coronary syndrome than whether or not they are managed invasively or medically.
The better survival associated with early invasive management of non-ST elevation acute coronary syndrome in this cohort are in keeping with the clinical benefits of angiography and revascularisation reported in clinical trials, including subgroups with pre-existing chronic kidney disease.2
Although episodes of acute kidney injury have been linked to an increased risk of end stage renal disease,18
we did not observe a higher risk of end stage renal disease in people with otherwise similar characteristics who received early angiography despite the higher risk of acute kidney injury, even among strata with lower baseline estimated glomerular filtration rate. Radiocontrast associated acute kidney injury is typically manifested by a small change in serum creatinine levels, rarely leads to acute dialysis, and is usually reversible.10
Our findings suggest that the majority of such additional episodes of acute kidney injury associated with invasive procedures may confer relatively low risks of progression to end stage renal disease, although further studies are needed to help predict those at risk of progressive chronic kidney disease after acute kidney injury.
Strengths and limitations of this study
Our study has several strengths. Firstly, unlike previous observational studies examining the risk of acute kidney injury and subsequent clinical outcomes in the setting of percutaneous coronary intervention, our study enrolled all people with acute coronary syndrome within a geographical region. We also included a control group treated with conservative management, allowing us to determine the additional risks of events related to management relative to the risks that may occur as a result of individual comorbidities or other predisposing factors. Secondly, we used prospectively collected data to minimise misclassification and adjusted for important prognostic variables, including laboratory data, to reduce the potential for confounding. Finally, we used a propensity score matching approach to minimise treatment by indication bias.
Our study also has some limitations. Firstly, our study was observational in design and thus, unlike a randomised trial, does not prove a causal relation between treatment strategy and outcomes. However, the renal outcomes we examined have not been studied in trials of early invasive versus conservative treatment for non-ST elevation acute coronary syndrome, despite multiple observational studies linking acute kidney injury to adverse outcomes after coronary angiography and percutaneous coronary intervention. Furthermore, although we used a propensity score analysis to limit the potential for bias, residual confounding remains possible owing to unmeasured variables such as frailty, which may influence both treatment selection and outcomes. However, the strength of the treatment effect of early invasive treatment that we observed was similar to that observed in randomised trials of early invasive treatment for high risk patients, suggesting that propensity score matching possibly mitigated much of the treatment-selection bias.
Secondly, our study was conducted in a single geographical region in Canada, thus the availability and utilisation of cardiac catheterisation and rates of revascularisation (percutaneous coronary intervention and coronary artery bypass grafting) after non-ST acute coronary syndrome may differ in other settings. However, similar findings have been reported elsewhere, including the observation that patients with chronic kidney disease are less likely to receive invasive management despite better survival associated with these procedures irrespective of baseline estimated glomerular filtration rate.35
Thirdly, relatively few people in our study had admission estimated glomerular filtration rates <30 mL/min/1.73 m2
, nor did we have sufficient study size to further stratify outcomes based on albuminuria. The higher risk of acute kidney injury in these subgroups could have a larger implication on the absolute risk of acute dialysis and end stage renal disease, particularly in these high risk people.8
Finally, few patients developed acute kidney injury requiring dialysis or end stage renal disease, limiting the power of our study to exclude small differences in the risk of these outcomes between treatment strategies. Therefore, despite our findings, further trials remain necessary to examine renal outcomes, quality of life, and survival with early invasive treatments in people with moderate to advanced chronic kidney disease.
In conclusion, early invasive management of non-ST elevation acute coronary syndrome is associated with a small increase in the risk of acute kidney injury compared with a conservative management approach but is not associated with higher risks of in-hospital acute kidney injury requiring dialysis or long term risk of end stage renal disease. Given the improvement in cardiovascular outcomes and long term survival observed with early invasive management, these results suggest that invasive treatments should not be withheld solely because of concern they might increase the risk of kidney injury.
What is already known on this topic
- Acute kidney injury after invasive coronary procedures is associated with adverse outcomes, including end stage renal disease and death
- Fear of precipitating contrast induced acute kidney injury possibly contributes to underuse of invasive treatments for acute coronary syndrome in people at high risk of kidney disease
- Comparisons of renal outcomes between people treated with invasive versus conservative management are lacking
What this study adds
- People who received early invasive management for non-ST segment elevation acute coronary syndrome were modestly more likely to develop acute kidney injury
- After early invasive management the risks of requiring dialysis and long term risk of end stage renal disease were similar, and patients had better long term survival than those treated conservatively
- These findings were consistent across varying levels of baseline kidney function, suggesting similar relative risks and benefits of early invasive management in people with and without pre-existing kidney disease