BCL-2 gene study in septic patients with acute renal injury

Introduction: Sepsis is the development of organ dysfunction due to dysregulated host response to infection. For organ dysfunction, which is required in the diagnosis of sepsis, it is necessary to get a score of two or more in the Sofa score. Acute kidney injury (AKI) due to sepsis is seen in 15-20% of patients diagnosed with sepsis. As the severity of sepsis increases, the incidence of AKI also increases. In addition, AKI not only worsens the course of sepsis, but is also a predisposing factor in the development of recurrent sepsis due to susceptibility to infections in AKI. For this reason, it is important to recognize AKI early and understand its pathogenesis in sepsis. Age, gender, comorbidities and foci of infection, which are predefined risk factors for the development of AKI in sepsis, could not reliably explain the development of sepsis-related AKI. Therefore, genetic variability between individuals is thought to constitute an important part of AKI development. In our study, we planned to investigate whether BCL-2 genetic variation, which is the main modulator of cell death, increases the risk of developing AKI in patients with sepsis. Materials and Methods: This study, which was approved by the Düzce University Ethics Committee with decision number 2019/177, supported by the Scientific Research Projects with the project number 2019.04.03.1037 and carried out in accordance with the principles of the Helsinki Declaration, was carried out between 01.10.2019-15.01.2020. 49 patients hospitalized in Duzce University Research and Application Hospital Internal Medicine Intensive Care Unit were included. Patients who were hospitalized in the intensive care unit with a diagnosis of sepsis, who were 18 years of age or older, who accepted the study and who did not have end-stage renal failure were included in the study. Patients with a diagnosis of sepsis were divided into two groups as those with AKI (n=25) and those without AKI (n=24). BCL-2 genetic variation was evaluated in patients in both groups. Results: While the groups were homogeneously distributed in terms of age and gender; body weight, rates of antihypertensive and antithrombotic drug use, coronary artery disease, heart failure, and chronic kidney disease (CRF) were higher in the AKI group. Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II), creatinine values and high lactate values were statistically significantly higher in the group with AKI. The bicarbonate level was found to be significantly lower in the AKI group. The main reason for hospitalization in both groups was pneumonia (n=42, [85%]; n=13, [54.2%] in the control group; n=14, [56.0%] in the patient group) and the most common microorganisms were Klebsiella (n=11, [22%]), Acinetobacter (n=10, [20%]), Pseudomonas (n=8, [16%]) and S. aureus (n=6 [12%]), respectively. It was found that intensive care, hospital and long-term (6 and 12 months) mortality rates in the group with AKI were statistically significantly higher than the group without AKI. Two genetic variations of BCL-2 have been identified as "rs1801018" and "rs4987711". The rs1801018 variation was higher in the group with AKI (n=6, [25%] in the control group; n=16, [64%] in the patient group; p=0.003), while the genetic variation of rs4987711 was found only in the group with AKI (n=0, [0%] in the control group; n=2, [8%] in the patient group; p=0.003). In patients with BCL-2 genetic variation, the risk of developing AKI was 7.71 times higher and the risk of developing CRF was 4.73 times higher. In terms of mortality, the 6 and 12-month mortality rates were found to be 8.94 and 7.26 times higher, respectively, in those carrying BCL-2 genetic variation. Conclusion: BCL-2 genetic variation was found to be significantly higher in patients with AKI due to sepsis in the intensive care unit. Patients with BCL-2 genetic polymorphism were found to be 7.71 times more susceptible to AKI. In addition, it was observed that the 3 and 6 month mortality rate was higher in patients with genetic variation. Therefore, it is thought that the BCL-2 genetic variation can be considered as a risk factor for the development of AKI. Keywords: Sepsis, acute kidney injury, BCL-2, mortality