The role of circulating zonulin levels in patients with chronic kidney disease stages 3 to 5 not on dialysis

Abstract

Zonulin (Zo) has recently been identified as a marker of intestinal permeability. It has previously been linked to type 2 diabetes mellitus, obesity, and cardiovascular disease; however, its role in chronic kidney disease (CKD) remains unclear. This study aimed to investigate the relationship between Zo and systemic inflammation (SI), endothelial dysfunction (ED), and renal function in CKD patients. One hundred sixty-three participants were enrolled in this study and divided into 2 groups (patient and control) according to the presence of CKD stage 3 to 5 not on dialysis. Circulating Zo levels have been investigated as markers of intestinal permeability. Furthermore, vascular cell adhesion molecule 1 (VCAM-1) and Interleukin-6 (IL-6) have been used as biomarkers for ED and SI assessments, respectively. A total of 104 patients with CKD (mean age: 58.9 +/- 1.4) and 59 control subjects (mean age: 59.0 +/- 1.1) were included, with similar age (P = .934) and sex (P = .196) between the groups. In the comparison analysis, plasma Zo levels in the CKD group (166.16 +/- 53.54) were significantly higher than those in the control group (143.30 +/- 60.92) (P < .001). In the correlation analysis, the serum Zo level showed a positive correlation with claudin-3 (R = 0.612, P < .001), IL-6 (R = 0.307, P < .001), and creatinine (R = 0.313, P < .001) and a negative correlation with glomerular filtration rate (GFR) (r = -0.320, P < .001). On the other hand, there was no correlation between circulating Zo and VCAM-1 levels (r = -0.139, P = .081). Additionally, according to linear regression analysis, Zo level was significantly associated with GFR after adjusting for age and systolic blood pressure (beta = -0.918, P = .012). High serum Zo levels in patients with CKD reflect increased intestinal permeability and are associated with impaired renal function. Moreover, it was thought that Zo levels could be associated with SI; however, novel clinical studies are needed to elucidate their relationship with ED.