Systemic Expression of Oxidative DNA Damage and Apoptosis Markers in Acute Renal Graft Dysfunction

Abstract

Background: Acute renal graft dysfunction (AGD) is one of the primary complications after kidney transplantation. The aim of this study was to identify the systemic oxidative DNA damage and apoptosis markers in patients with AGD, which will aid the understanding of the underlying processes of the complication. Methods: A cross-sectional analytical study was conducted in renal transplant (RT) recipients with and without AGD. The follow-up time of patients was <1 year. Using the ELISA technique, the markers of oxidative DNA damage (8-hydroxy-2-deoxyguanosine and 8-oxoguanine-DNA-N-glycosylase-1) and apoptosis (caspase-3, caspase-8, soluble TNF receptor 1, and cytochrome C) were determined. Results: Donor age was significantly higher in patients with AGD versus those without AGD (43±11 years versus 34.1±10.6 years, respectively; p<0.001). Levels of 8-hydroxy-2-deoxyguanosine were also significantly higher in AGD patients than those without AGD (624.1±15.3 ng/mL and 563.02± 17.4 ng/mL, respectively; p=0.039) and the DNA repair enzyme 8-oxoguanine-DNA-N-glycosylase-1 was significantly diminished in AGD patients versus non-AGD patients (7.60±1.8 ng/mL versus 8.13±1.70 ng/mL, respectively; p=0.031). A significant elevation of soluble TNF receptor levels in AGD patients was also found versus those without AGD (1178.6±25.2 ng/mL versus 142.6±39 ng/mL, respectively; p=0.03). Caspase-3 levels were higher in patients with AGD (1.19±0.21 ng/mL) versus those without AGD (0.79±0.11 ng/mL; p=0.121) and was also significantly augmented in AGD versus healthy control subjects (0.24±0.1 ng/mL; p=0.036). Cytochrome c in AGD patients was 0.32±0.09 ng/mL and 0.16±0.03 ng/mL in those without AGD versus 0.08±0.01 ng/mL in healthy controls (p=0.130 and p=0.184, respectively). Conclusion: These findings suggest that oxidative DNA damage with insufficient DNA repair and higher levels of caspase-3 compared to controls are markers of apoptosis protein dysregulation in AGD patients.