#612 Serum citrulline level is associated with oxidative stress and chronic kidney disease progression

Abstract

Abstract Background and Aims Citrulline, an α-amino acid crucial for the urea cycle and nitric oxide production, plays a protective role against free radicals and is indirectly related to protein metabolism. It is synthesized in the intestine and efficiently absorbed by the proximal renal tubules, where it is converted to urea via arginine. Although citrulline has multiple physiological effects, its involvement in the progression of chronic kidney disease (CKD) has not been explored. This cross-sectional study aimed to investigate the relationship between serum citrulline levels, CKD progression, and markers of oxidative stress. Method A total of 135 subjects were enrolled in this cross-sectional study. This cohort included 30 relatively healthy individuals who constituted the control group and 105 CKD patients who were categorized according to their estimated glomerular filtration rate (eGFR). We measured serum citrulline concentrations along with markers of oxidative stress, including paraoxonase 1 (PON-1), myeloperoxidase (MPO), and malondialdehyde (MDA), using the spectrophotometric method. Data were expressed as mean (M) and standard deviation (SD) or median and interquartile range [Me (Q25-Q75)] according to the data distribution and compared with the Kruskal-Wallis test. Spearmen correlation test was performed to evaluate the correlation between the studied data. Results Our findings revealed a significant increase in citrulline and MDA concentrations and MPO activity and a significant decrease in PON-1 in the CKD group compared with the control group. Moreover, a significant association emerged between serum citrulline levels and the severity of CKD, as determined by eGFR. Specifically, patients in advanced CKD stages exhibited elevated serum citrulline concentrations in contrast to those in earlier stages (Table 1). Furthermore, a significant correlation was established between serum citrulline and oxidative stress markers, with higher citrulline levels positively associated with increased concentrations of MDA (r = 0.46, p = 0.002) and heightened MPO activity (r = 0.85, p < 0.001), and demonstrating an inverse relationship with PON-1 in CKD stages 1-2 and 5 (r = -0.64, p < 0.001 and r = -0.47, p = 0.004, respectively). Conclusion This cross-sectional study suggests that serum citrulline level is associated with both CKD progression and oxidative stress intensity in patients with CKD. These findings highlight the potential role of citrulline as a biomarker for CKD progression and its implications in the management of oxidative stress in CKD. Further research is warranted to elucidate the underlying mechanisms and explore the therapeutic potential of citrulline supplementation in CKD patients.