Predictors of acute kidney injury in patients with ST-segment elevation myocardial infarction complicated by cardiogenic shock who underwent percutaneous coronary intervention

Introduction

ST-segment elevation myocardial infarction (STEMI) is the main etiological factor in the development of cardiogenic shock (CS) [1]. The incidence of this complication in patients with STEMI has been 4–15% over the past decades [2][3]. However, being not the most frequent complication, CS remains the leading cause of death in these patients [4]. It should be noted that 76% of deaths in STEMI in the first seven days are due to CS [5].

STEMI complicated by CS is often accompanied by acute renal dysfunction. The prevalence of acute kidney injury (AKI) in this category of patients reaches 55% [1][6]. The AKI development worsens the short-term and long-term prognosis of these patients, as it leads to an increase in the hospitalization duration, an increase in hospital lethality and mortality in the remote period [1][4][6][7].

Percutaneous coronary interventions (PCIs) are currently an integral part of the treatment of patients with STEMI and CS, and iodine-containing contrast media (ICM) used in these invasive procedures are an additional damaging factor leading to AKI development [8]. However, few studies examining AKI predictors in patients with STEMI and CS have generally included both patients who underwent PCI and those who did not undergo PCI. In this regard, the risk factors for AKI in patients with STEMI and CS who underwent PCI should be studied.

This research was aimed at studying the predictors of AKI development in patients with STEMI and CS who underwent PCI.

Materials and methods

A prospective open-label observational study included 109 patients with STEMI and CS admitted for treatment at the cardiology department of the vascular center of the Ivanovo Regional Clinical Hospital during 2020.

Inclusion criteria were as follows: patients with STEMI and CS who underwent emergency PCI; men and women; signed voluntary informed consent.

Exclusion criteria were the following ones: history of intravascular use of ICM within 30 days prior to hospitalization; arrhythmogenic and hypovolemic CS; acute and chronic primary kidney disease; nephrotic syndrome; autoimmune diseases; chronic kidney disease requiring renal replacement therapy; severe intercurrent somatic pathology that has an independent negative impact on the prognosis (acute bacterial and viral infection, chronic diseases at the stage of decompensation and malignant neoplasms); refusal of the patient to be included in the research.

The diagnosis of STEMI on the electrocardiogram was established according to current clinical guidelines [9].

The CS diagnosis was established on the basis of a decrease in systolic blood pressure below 90 mmHg for more than 30 minutes or the need for infusion of vasopressors to maintain systolic pressure over 90 mmHg and the presence of signs of organ hypoperfusion [9].

AKI was diagnosed according to the KDIGO guidelines when the serum creatinine increase was more than or equal to 26.5 µmol/L compared to a baseline within 48 hours or more than or 1.5 times higher compared to its known or presumed basal level within 7 days with the exclusion of other reasons [10]. The initial level of creatinine in the blood was taken as the value of plasma creatinine obtained upon admission of the patient to the hospital before PCI. The stage of AKI development was established taking into account the severity of renal dysfunction [10].

Upon admission to the hospital, all patients with STEMI underwent general clinical studies; the content of troponins, lipids, and glucose in the blood was determined; electrocardiography, echocardiography, and chest radiography were performed. Coronary angiography and stenting of the coronary arteries were performed for all patients on the day of admission to the hospital by puncture of the right radial artery using ioversol or iohexol ICM. Plasma creatinine and glomerular filtration rate (GFR) calculated using the CKD-EPI equation were determined before PCI 24 and 48 hours after the intervention.

Examination of patients was performed on the basis of the informed voluntary consent of the patient in accordance with the order No. 3909n of the Ministry of Health and Social Development of the Russian Federation of April 23, 2012 (registered by the Ministry of Justice of the Russian Federation on May 5, 2012 under No. 240821) in compliance with ethical principles. The research was conducted in accordance with international GCP standards.

The general characteristics of the patients included in the research are presented in Table 1.

Statistical data processing was conducted using the IBM SPSS Statistics 23 program. The sample was assessed using the Shapiro-Wilk test to check normal distribution. Quantitative features were presented as the arithmetic mean of the variation series and its standard deviation (M±SD) with a normal distribution, or the median and interquartile range (Me [Q25;Q75]) with a non-normal distribution. Qualitative data were expressed as absolute and percentage values ​​(n (%)). The analysis of the statistical significance of differences between quantitative indicators was conducted using the parametric Student's t-test or the non-parametric Mann-Whitney U-test, between qualitative indicators – using the χ² test. Factors associated with the probability of AKI development were identified using the method of simple logistic regression. Multiple logistic regression was used to identify predictors that independently affected the AKI development. The results of both regression analysis methods were presented with an indication of the odds ratio and its 95% confidence interval for each significant variable. All differences were considered statistically significant at p<0.05.

Results

The research has shown that among the patients with STEMI and CS who underwent PCI, AKI was detected in 33 people, which accounted for 30.3% of all patients; stage 1 AKI was defined in 78.8% (n=26) of patients, stage 2 AKI – in 18.2% (n=6) of patients, and stage 3 AKI – in 3.0% (n=1) of patients. In all cases, AKI was detected within 48 hours after PCI. Renal replacement therapy for advanced AKI was not performed in patients in this research.

Thus, all studied patients with STEMI and CS were divided into two groups. The observation group included 33 patients with AKI, the comparison group included 76 patients without AKI.

The initial clinical and demographic characteristics of patients in the studied groups are presented in Table 1.

Significant differences were obtained between the compared groups in terms of mean age, the number of patients older than 70 years, the presence of chronic kidney disease and chronic heart failure with preserved and reduced ejection fraction. In patients of both groups with chronic kidney disease, the stage of the disease corresponded to C3a and C3b.

For most of the initial laboratory parameters, the groups were comparable to each other (Table 2). In patients with AKI, baseline plasma creatinine was significantly higher (p=0.003), and GFR was lower (p=0.001). GFR less than 60 ml/min/1.73 m² was more common in the observation group than in the comparison group (54.5% (n=18) and 22.4% (n=17), respectively, p=0.001). Two days after PCI, there were significant differences between the compared groups in terms of plasma creatinine and GFR (p<0.001).

Analysis of the dynamics of these indicators after the emergency intervention revealed that compared with the initial data 48 hours after PCI, the amount of creatinine in the blood increased significantly (126.8 [ 116.6; 137.1] and 177.7 [ 168.8; 186.6] µmol/L, respectively, p<0.001) and GFR decreased (55.8 [ 50.5;61.1] and 36.9 [ 30.4;42.9] ml/min/1.73 m², respectively, p<0.001) only in patients with AKI. In the group without AKI, no significant change in these parameters after PCI was defined. The average increase in plasma creatinine two days after the intervention in the AKI group was 50.9 [ 48.9; 52.9] µmol/L, in the comparison group — 6.2 [ 5.1; 7.4] µmol/L (p<0.001).

In patients with AKI when compared to patients without acute kidney dysfunction, the left ventricular ejection fraction upon admission to the hospital was lower (35.1 [ 29.3; 40.9] and 37.8 [ 33.0; 42.6], respectively, p=0.043), more often the value of this indicator was below 40% (75.8% and 53.1%, respectively, p=0.017).

According to the results of coronary angiograms, three-vessel lesions of the coronary bed were significantly more common in patients with AKI than in patients of the comparison group (63.6% (n=21) and 40.8% (n=31), respectively, p=0.028). No significant differences in the occurrence frequency of single-vessel (21.2% (n=7) and 35.5% (n=27), respectively, p=0.141) and double-vessel (15.2% (n=5) and 23.7% (n=18), respectively, p=0.311) lesions of the coronary bed were revealed. Patients with AKI had a significantly higher mean number of coronary occlusions (2.8 [ 1.7;3.9] and 2.2 [ 1.3;3.1], respectively, p=0.039) and hemodynamically significant stenoses (1.3 [ 0.8;1.8] and 1.1 [ 0.6;1.5], respectively, p=0.015) compared to patients without acute renal dysfunction.

The mean time from the onset of pain to PCI was longer in patients with AKI (316.2 [ 285.6; 346.8] min and 201.4 [ 171.4; 231.4] min, respectively, p = 0.001). In all cases, PCI ended with symptomatic artery stenting. In the observation group, the average number of implanted stents was 1.6 [ 1.01;2.2]; in the comparison group, the average number of vascular prostheses was 1.5 [ 0.9;2.1] (p=0.001). No significant differences between the groups in terms of the ICM volume used during emergency intervention (185.6 [ 149.7;221.5] ml and 161.2 [ 126.1;216.3] ml, respectively, p = 0.113) were defined. However, the value of the "volume of ICM/GFR" ratio was higher in patients with AKI than without AKI (3.3 [ 3.0;3.6] and 2.9 [ 2.6;3.4], respectively, p= 0.032).

Intra-aortic balloon pump counterpulsation was used only in patients in the AKI group (12.1% (n=4)).

The research allowed revealing the factors associated with AKI development in patients with STEMI and CS using the method of simple logistic regression (Table 3). After conducting a multiple logistic regression analysis, step by step including the above features, significant independent variables were defined that affected AKI development in the studied category of patients (Table 3). For the multiple logistic regression model as a whole, Wald's χ² was 16.49, p<0.001.

Discussion

The presence of CS in patients with STEMI is already a predictor of AKI since renal hypoperfusion against the background of an acute decrease in systemic hemodynamics leads to ischemia of the organ. However, acute renal dysfunction does not develop in all patients with CS which means that AKI should be considered as a result of the influence of a combination of factors including those caused by both the patient's own clinical and anamnestic characteristics and the toxic effect of ICM on the kidneys during PCI [10].

According to the studies, AKI develops more often in elderly patients with STEMI and CS [6][12] which, apparently, is due to the presence of underlying cardiovascular diseases and other comorbid pathologies that initially worsen kidney function. In the research, the majority of patients with AKI were over 70 years of age.

The research results demonstrate that the presence of chronic kidney disease and chronic heart failure increases the risk of AKI development in patients with STEMI and CS, including those who underwent PCI, which is consistent with the results of other studies [1][6][11–13].

In the analyzed groups, the level of leukocytes and troponins in the blood on the first day after hospitalization was significantly higher in patients with AKI. According to the studies, the systemic inflammatory reaction, which occurs with heart muscle necrosis and progressive tissue hypoxia against the background of shock contributing to the aggravation of myocardial dysfunction, impacts the development and progression of CS in patients with STEMI [14]. In addition, a number of studies have demonstrated an interrelation between the development of AKI in patients with STEMI, including those after PCI, and an increase in the levels of inflammatory markers in the blood, for example, highly sensitive C-reactive protein [15][16]. C-reactive protein is not just a marker of inflammation; it allows reducing the production of nitric oxide and weaken antioxidant protection, which leads to endothelial dysfunction, a decrease in the activity of renal vasodilators, and this, in turn, is the main factor in the AKI development [16].

The pathomorphology of CS in patients with STEMI is based on a decrease in myocardial contractility against the background of acute ischemia and the heart muscle necrosis. This leads to the formation of a vicious circle, i.e., to a decrease in ejection fraction and aggravation of myocardial ischemia, which, in turn, further worsen the systolic function of the heart [14], and hence worsen the peripheral perfusion of kidneys. In this regard, it has been proven that a decrease in the left ventricular ejection fraction of less than 40% is an independent factor in the development of AKI in patients with STEMI and CS [6], which was also reflected in the research.

Analysis of the coronary angiography results has shown that multiple, three-vessel coronary artery disease was observed in patients with STEMI and CS with AKI more often than in patients without acute kidney dysfunction. Similar observations were identified by other researchers only in relation to hemodynamically stable patients with STEMI [17]. Although these factors did not have an independent effect on the development of AKI in this category of patients, they could exacerbate ischemia and systolic myocardial dysfunction already existing in patients with STEMI and CS.

ICM can also have a certain impact on the development of AKI after PCI in patients with STEMI and CS. It has been established that ICM disrupt renal hemodynamics, which induces medullary ischemia primarily due to a direct cytotoxic effect on the glomerular endothelium and tubular epithelium, as well as an indirect effect on the viscosity of blood and urine followed by an increase in intratubular pressure and a decrease in the filtration function of the kidneys [17]. It has been revealed that contrast-induced AKI develops more often in patients with CS than in hemodynamically stable patients [11]. It is assumed that the prognostic role in the AKI development after PCI in patients with STEMI is played not so much by the volume of contrast injected but by the "volume of ICM/GFR" ratio [18]. This research has shown that in patients with STEMI and CS in the group with AKI, with an insignificant difference between the groups in terms of the volume of contrast used during the intervention, the "volume of RCP/GFR" ratio was significantly higher. Some studies demonstrate that unstable hemodynamics and GFR less than 60 ml/min/1.73 m² rather than the volume of injected ICM have a certain impact on the development of AKI in patients with STEMI after PCI [19].

Conclusion

This research has shown that the risk of AKI in patients with STEMI and CS undergoing PCI was associated with the patient's age of over 70 years, the presence of GFR less than 60 ml/min/1.73 m² at admission to the hospital, and the left ventricular ejection fraction less than 40%. It is necessary to dynamically control the level of creatinine in the blood during the stay in the hospital in this category of patients in order to timely diagnose and correct acute kidney dysfunction.