Alaa Efat1, Sabry Shoeib1, Eman Ebrahim2, Zeinab Kassemy3, Hanan M Bedair4, Mohammed Abozenah5. 1. Hematology Unit, Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin Al Kawm, Egypt. 2. Medical Graduate Student, Faculty of Medicine, Menoufia University, Shibin Al Kawm, Egypt. 3. Community and Public Health Department, Faculty of Medicine, Menoufia University, Shibin Al Kawm, Egypt. 4. Clinical Pathology, National Liver Institute, Menoufia University, Shibin Al Kawm, Egypt. 5. Cardiovascular Medicine, Heart and Vascular Department, University of Massachusetts Chan Medical School-Baystate Medical Center, Springfield, MA, USA. mohammed.abozenah@baystatehealth.org.
Abstract
BACKGROUND: Acute kidney injury (AKI) is one of the most frequent pathophysiologic disorders encountered in hospitalized patients, with sepsis frequently implicated in pathogenesis. Reactive oxygen species (ROS) seem to have a significant contribution to sepsis-induced AKI. Proposed mechanisms include induction of cell membrane lipid peroxidation, protein denaturing, and direct DNA damage, all of which have deleterious effect. These changes constitute oxidative injury to the kidneys. OBJECTIVE: To evaluate the antioxidant actions of indirect bilirubin and uric acid on outcomes of sepsis-associated AKI. METHODS: Ninety-eight patients admitted to the intensive care unit (ICU), at a large tertiary center, with sepsis and AKI were evaluated for serum levels of uric acid, bilirubin (primarily indirect), and procalcitonin. The primary endpoints studied were the need for hemodialysis and death. RESULTS: Thirty-two (33%) patients developed AKI requiring hemodialysis (HD). These patients had higher SOFA scores (p < 0.001) and lower levels of indirect bilirubin (p < 0.001) compared to those not requiring HD. There was no statistically significant difference in serum uric acid levels. Logistic regression analysis identified creatinine level, total and indirect bilirubin levels, and leukocyte count as significant predictors of patient death. CONCLUSION: Higher leukocyte counts and creatinine levels were independently associated with poor outcomes in ICU patients with sepsis. Additionally, lower indirect bilirubin levels were also noted to be associated with similar outcomes. The latter provides insights into oxidative stress as a major player in the pathogenesis of sepsis-induced AKI, with a potential protective role of indirect bilirubin.
BACKGROUND: Acute kidney injury (AKI) is one of the most frequent pathophysiologic disorders encountered in hospitalized patients, with sepsis frequently implicated in pathogenesis. Reactive oxygen species (ROS) seem to have a significant contribution to sepsis-induced AKI. Proposed mechanisms include induction of cell membrane lipid peroxidation, protein denaturing, and direct DNA damage, all of which have deleterious effect. These changes constitute oxidative injury to the kidneys. OBJECTIVE: To evaluate the antioxidant actions of indirect bilirubin and uric acid on outcomes of sepsis-associated AKI. METHODS: Ninety-eight patients admitted to the intensive care unit (ICU), at a large tertiary center, with sepsis and AKI were evaluated for serum levels of uric acid, bilirubin (primarily indirect), and procalcitonin. The primary endpoints studied were the need for hemodialysis and death. RESULTS: Thirty-two (33%) patients developed AKI requiring hemodialysis (HD). These patients had higher SOFA scores (p < 0.001) and lower levels of indirect bilirubin (p < 0.001) compared to those not requiring HD. There was no statistically significant difference in serum uric acid levels. Logistic regression analysis identified creatinine level, total and indirect bilirubin levels, and leukocyte count as significant predictors of patient death. CONCLUSION: Higher leukocyte counts and creatinine levels were independently associated with poor outcomes in ICU patients with sepsis. Additionally, lower indirect bilirubin levels were also noted to be associated with similar outcomes. The latter provides insights into oxidative stress as a major player in the pathogenesis of sepsis-induced AKI, with a potential protective role of indirect bilirubin.
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