Role of urinary H2O2, 8-iso-PGF2α, and serum oxLDL/β2GP1 complex in the diabetic kidney disease

Abstract

Oxidant species is reported as a major determinant in the pathophysiology of diabetic kidney disease. However, reactive oxygen species (ROS) formation in the initial phase and progressing phase of diabetic kidney disease remains unclear. Therefore, we conducted this study to find out what ROS and their modified product are associated with eGFR in type 2 diabetes mellitus (T2DM) patients. A cross-sectional study was performed on 227 T2DM patients. The study subjects were divided into three groups based on their eGFR stage (Group 1, eGFR > 89 ml/min/1.73 m2; Group 2, eGFR = 60–89 ml/min/1.73 m2; and Group 3, eGFR < 60 ml/min/1.73 m2). Enzyme-linked immunosorbent assay (ELISA) was used to measure serum oxLDL/β2GPI complex and urinary 8-iso-PGF2α, while ferrous ion oxidation xylenol orange method 1 (FOX-1) was used to measure urinary hydrogen peroxide (H2O2). H2O2 significantly decreased across the groups, whereas OxLDL/β2GPI complex increased, but not significant, and there was no trend for 8-iso-PGF2α. Consistently, in the total study population, only H2O2 showed correlation with eGFR (r = 0.161, p = 0.015). Multiple linear regression analysis showed that significant factors for increased eGFR were H2O2, diastolic blood pressure, and female. Whereas increased systolic blood pressure and age were significant factors affecting the decrease of eGFR. We also found that urinary H2O2 had correlation with serum oxLDL/β2GPI complex in total population. This finding could lead to further research on urinary H2O2 for early detection and research on novel therapies of diabetic kidney disease.

Klotho inhibits renal ox-LDL deposition via IGF-1R/RAC1/OLR1 signaling to ameliorate podocyte injury in diabetic kidney disease

“…Ox-LDL is more prone to deposit on the inner walls of blood vessels, leading to atherosclerosis and other cardiovascular complications compared to normal LDL. Several studies have established an association between plasma ox-LDL and adverse outcomes in DKD, including mortality, deterioration of kidney function, and proteinuria [ 10 , 11 ]. Furthermore, the injury caused by ox-LDL in DKD involves oxidative stress and cellular inflammation, facilitated by scavenger receptors such as CD36, SR-A1, and OLR1 [ 12 , 13 ].…”

Kidney Transplant Recipients Show Limited Lung Diffusion Capacity but Similar Hydrogen Peroxide Exhalation as Healthy Matched Volunteers: A Pilot Study

“…Hydrogen peroxide (H 2 O 2 ) is one of the most over-produced ROS in CKD patients [1,2]. Increased concentrations of H 2 O 2 were reported in the urine, plasma, and exhaled breath condensate (EBC) of the analyzed CKD patients [10][11][12][13][14][15]. EBC is a composition of (A)particles or droplets that are aerosolized from the airway lining fluid, (B)-distilled water that arises through condensation of water vapor from the airway surface, and (C)-water soluble volatiles that are exhaled and absorbed into the condensing breath [16].…”