Molecular patterns of oxidative stress in drug-induced nephropathy

Introduction: Drug induced kidney disorder is a frequent adverse event which contributes to morbidity and even incapacitation. The discovery and development of novel biomarkers and local (renal) response mechanisms, are needed for effective prevention of drug-induced nephrotoxicity. Objectives: The main purpose of our study was to investigate the oxidative modifications of proteins in blood plasma and erythrocytes of patients with drug-induced nephropathies. Patients and Methods: Around105 patients were divided into two groups: first group was represented by patients with psychotropic drug-induced nephropathy; the second one consisted of patients received nonsteroidal anti-inflammatory drugs (NSAIDs). Advanced oxidation protein products (AOPPs) were measured by Witko-Sarsat method. Protein reactive carbonyl derivatives (PRCD) were assayed in blood plasma and erythrocytes by the Levine method. Neutrophil gelatinaseassociated lipocalin (NGAL) was determined with the use of a commercially available ELISA kit. Results: Carbonyl derivatives are significantly higher in red blood cells of the 1st and 2nd group patients compared to the control subjects. AOPP statistically increased both in patients with various types of drug nephropathy and in patients with chronic kidney disease (CKD) compared with the control group. The NGAL was significantly higher in all groups compared to the control subjects. Conclusion: The patients with drug-induced nephropathy have increased level of oxidative stress products and response NGAL reaction. The mechanisms that lead to the development of oxidative stress and the production of modified proteins are different in patients treated with different drugs. Establishing patterns of cell-molecular interaction permit the drug-induced nephropathy to be timely diagnosed and therapeutic programs to be optimized

Serum neutrophil gelatinase-associated lipocalin and oxidized neutrophil proteins in patients with nephropathy caused by acute alcohol poisoning

Introduction: Alcohol use has been identified as a major risk factor for disease burden and premature mortality. Objectives: We studied the serum neutrophil gelatinase-associated lipocalin (NGAL) and advanced oxidation protein product (AOPP) concentrations in neutrophils to assess the possibility of their using for the early detection of kidney damage in patients with acute alcohol poisoning (AAP). The impact of eGFR (estimated glomerular filtration rate) on the NGAL and AOPP levels was also studied. Patients and Methods: The study included 89 patients with AAP. Healthy individuals and patients with chronic kidney disease (CKD) served as comparison groups. Participants were represented by men, aged between 20 and 40 years. Results of laboratory tests of kidney function were also taken into account. Serum NGAL level was measured using ELISA kit. AOPP was determined using the method of Witko-Sarsat et al. Results: We detected a significant increase in serum NGAL and AOPP level both in toxic nephropathy with a clinical picture of acute kidney injury (AKI) and in the "preclinical stage" of kidney damage. Hence a single trend in the changes of these indicators existed in patients with AAP. At the same time, our study revealed opposite trends in patients with CKD. There was no significant increase in serum NGAL in patients with CKD. Conclusion: We propose to consider an increased eGFR together with an increased serum NGAL concentration in patients with AAP as the stage, preceding the nephropathy or AKI, even in the absence of clinical and laboratory signs of impaired renal function