Overall, the prevalence of AKI in the setting of MI is 16%. Patients with AKI had a substantially higher risk of mortality than those without AKI. These observations persisted amongst those who did not experience in-hospital shock, in-hospital CABG, or have pre-existing CKD at baseline, all risk factors for AKI. Finally, patients with AKI are at a substantially higher risk of in-hospital major bleeding events, despite lower rates of invasive strategies.
The prevalence of AKI in our study was 16%, a rate that is comparable to what has been previously reported in diverse clinical settings.1;8;18;19
Following cardiac surgery, AKI may be as high as 24%,10
with up to 1.1% of patients requiring dialysis.20
When AMI is complicated by cardiogenic shock, AKI may affect more than half of all patients.21
Our study adds to the literature by extending what is known about the rates of in-hospital mortality in association with AKI in the setting of AMI. Scant literature exists that has systematically examined the association between AKI and mortality in the short-term setting. In a single-center study of 97 STEMI patients who required primary percutaneous coronary intervention and intra-aortic balloon pump, the AKI-associated mortality rate was 50%, with an in-hospital mortality relative risk of 12.3.21
Similarly, among 1038 patients who presented with STEMI at a medical center in Israel, worsening renal function (defined as an increase in serum creatinine of at least 0.5 mg/dl) was associated with an 11.4-fold increased risk of in-hospital mortality.8
Our results complement these findings in a substantially larger sample size using contemporary data, showing an increased mortality risk among patients admitted with MI with and without hemodynamic compromise and show a gradient of risk across increasing severity of AKI.
Outside of the AMI setting, substantial short-term increased risks associated with AKI have been observed. Among 27,068 patients who underwent coronary angiography over a 12-year period, small changes in serum creatinine (0.25-0.50 mg/dl) were associated with a 1.83 increased risk of mortality, whereas patients with a >1.0 mg/dl increase in serum creatinine had a 3.0-fold increased risk of mortality.22
These estimates are lower than those in the present work, and may in part represent the lower risk clinical setting, as well as selection bias in terms of patients selected to undergo coronary catheterization. Similarly, in a sample of 19,982 adults admitted to an urban medical center, patients with in-hospital increases in serum creatinine had a higher risk of mortality with odds ratios ranging from 4.1 to 16.4 for serum creatinine increases of 0.3 mg/dl to 2.0 mg/dl.1
Also, compared to patients without an increase in serum creatinine, adjusted hospitalization costs were more than $22,000 higher amongst those most severely affected.1
While physicians are generally aware of the risk of AKI associated with coronary angiography and guidelines have recommended measures to minimize this risk,23
our data highlight that AKI is observed in the MI setting regardless of treatment strategy and portends a risk of adverse outcomes.
Complications associated with AKI are particularly pronounced following cardiac surgery. A recent analysis of a multicenter cohort of 3500 adults who underwent cardiac surgery demonstrated that participants with as little as a 25% decrease in eGFR had a 4.0-fold increased risk of post-operative mortality, with rates as high as 9.5-fold increased when eGFR declined by at least 75%.10
The literature is far more robust in examining the association between AKI and longer-term mortality. Not surprisingly, as the length of time from the index event increases, relative increases in mortality rates appear lower. The long-term association of AKI with mortality was examined among 147,007 Medicare patients who presented with AMI from 1994 to 1996. At 10 years, the hazards for mortality ranged from 1.15 (for mild AKI) to 1.33 (for severe AKI).5
Similar findings were observed among 87,094 Medicare patients admitted to US hospitals between 1994 and 19959
and on the Survival and Ventricular Enlargement (SAVE) trial.7
A large meta-analysis of 48 studies comprised of 47,017 patients demonstrated a risk of death of 2.59 among studies with follow-up of at least 6 months.2
Finally, data from 920,985 patients in the Alberta Kidney Disease Network highlights the high longer-term risks associated with AKI, as well as the important contributions of baseline kidney function and proteinuria as an important predictor of disease.4
Taken together, these findings highlight the higher absolute and relative risk of death associated with AKI.
A striking finding from our work was the high rates of in-hospital bleeding events among those with worsening AKI, despite lower rates of usage of oral and intravenous antiplatelet agents. The reason for this is unclear, and may be related to the co-morbidities present in our patients with worsening AKI and the relationship between kidney and platelet dysfunction. Nonetheless, treatment algorithms should take worsening renal function in the AMI setting into account when making use of these agents such as updated dosing of renally-cleared medications including anticoagulants and antiplatelet agents.
There are several implications of this work. First, the prevalence of AKI in the AMI setting is high, and clinicians need to be aware of this important complication. Second, even small increases in serum creatinine are associated with increased risks of bleeding and in-hospital mortality. Particularly notable is the elevated risk of mortality among patients who did not experience in-hospital shock, undergo cardiac surgery, or have baseline CKD, underscoring the impact of AKI even without these important risk factors. Further, clinicians should recognize that AKI is a marker of risk in the setting of MI and is not solely associated with cardiac catheterization and exposure to intravenous contrast agents. Thus, efforts to better incorporate markers of AKI into risk prediction models in the AMI setting, as well as efforts to prevent AKI are critically important and may be a viable method for reducing mortality in the AMI setting. Given the importance of AKI in AMI, AMI registries should seek to collect multiple measures of serum creatinine, including discharge creatinine data to measure rates of recovery.
The strength of our work lies in the large, contemporary sample of MI patients. Further, we assessed outcomes in-hospital, which represents a high-risk setting for patients with AKI. Some limitations warrant mention. Our baseline serum creatinine measures were obtained on admission. Thus, we cannot exclude the possibility that the MI process itself may have already lead to an increase in serum creatinine; this would have lead us to underestimate the magnitude of AKI in our sample and would likely bias our findings towards the null. Second, we used a modified version of the AKIN11
criteria to define AKI, as information on urinary output was not available in our study sample. Universal definitions of AKI do not exist, although leading definitions put forward include AKIN11
In sensitivity analyses, we demonstrated comparability of an AKI definition based on percent creatinine changes. We do not have information collected on the amount of contrast administered during catheterization, bypass times during CABG, nor detailed information on the length of hypotensive episodes during hospitalization. Our registry consists of in-hospital mortality, but not long-term follow-up. We have information on baseline and peak serum creatinine, but not intercurrent creatinine. In addition, we do not have information on acute dialysis. Patients in whom serum creatinine was not collected (and hence excluded from our analysis) were less healthy. We have dates but not times for the in-hospital adverse events in our analysis, limiting our ability to finely assess temporality between AKI and in-hospital adverse outcomes. We do not have information on stopping and restarting inpatient medications. Some of the data presented in are unexpected, such as dyslipidemia in association with lower rates of AKI. Given the observational nature of our dataset, we are unable to fully dissect these relationships; further research in more controlled settings may be warranted. Finally, AKI is associated with a multitude of co-morbidities known to be associated with mortality in the MI setting. Thus, we cannot exclude the role of residual confounding in our associations. While we cannot determine a causal relationship between AKI and mortality or bleeding, it does not detract from the use of AKI as a marker of risk.
AKI occurs in 16% of patients hospitalized for acute MI. This common complication is strongly associated with mortality and bleeding. Recognition of these risks and employing strategies to avoid AKI may improve outcomes in MI.