The Role of Oxidative Stress and NADPH Oxidase P22phox Polymorphism in Acute Kidney Injury Patients The Role of Oxidative Stress and NADPH Oxidase P22phox Polymorphism in Acute Kidney Injury Patients

Abstract

Abstract: Acute kidney injury (AKI) is a common condition with significant associated morbidity and mortality. Although several studies have been done to understand the molecular and biochemical mechanisms of kidney injury. Results were static over the last 30 years. Increased production of reactive oxygen species (ROS) is thought to play a major role in the pathogenesis of AKI and its complications. The NADPH oxidase complex is an important source of ROS in AKI. Its p22 subunit is polymorph with a C242T variant that changes histidine-72 for a tyrosine in the potential heme binding site. The aim of this study was to investigate the occurrence of this polymorphism in 75 patients with AKI and correlate the genotype to the extent of the load of the circulating ROS and its association with the unfavorable course of the disease. This study included 75 hospitalized patients in the Internal Medicine Department Menofiya University Hospital with established AKI. We had done genotyping for the C242T polymorphism of the p22 subunit of the NADPH oxidase gene using restriction fragment length polymorphism (RFLP) technique. The extent of the ROS load was estimated by measuring the level of plasma nitrotyrosine level and then correlation to the severity of the course of the disease and its outcome was made. The results revealed that, compared to CC group, the T-allele carrier was associated with higher levels of serum urea, creatinine and plasma nitrotyrosine (p<0.01) and the levels of plasma nitrotyrosine are correlated with age of the patient and length of hospital stay. Also the T-allele carries (CT and TT groups) showed higher cumulative probability of remaining hospitalized, while there was no significant difference concerning requirement for dialysis, for ICU admission and dialysis dependency. It is concluded that the polymorphism C242T in the gene encoding p22phox of NADPH oxidase is associated with the severity of the course of the disease and the adverse outcome in cases with AKI