Serum zonulin levels and their association with inflammatory and oxidative stress biomarkers in patients undergoing maintenance hemodialysis

Abstract

Background

Maintenance hemodialysis (HD) is accompanied by persistent inflammation, oxidative stress, and disturbances of the intestinal barrier.

Objective

To compare serum zonulin concentrations between patients receiving maintenance HD and healthy controls and to evaluate their associations with interleukin-6 (IL-6), malondialdehyde (MDA), and total antioxidant status (TAS).

Methods

This comparative cross-sectional study included 180 participants: 90 patients with end-stage renal disease receiving maintenance HD and 90 age- and sex-comparable healthy controls. Predialysis blood samples were analyzed for serum zonulin, IL-6, and MDA by enzyme-linked immunosorbent assay and for TAS by a colorimetric assay. Group differences were evaluated using independent-samples t-tests, associations using Pearson's correlation, and adjusted relationships using multivariable linear regression.

Results

Compared with controls, the HD group had higher serum zonulin, IL-6, MDA, urea, creatinine, and phosphorus concentrations and lower TAS, albumin, calcium, and hemoglobin values (all P < 0.001). Within the HD group, zonulin correlated positively with IL-6 (r = 0.644, P < 0.001) and MDA (r = 0.782, P < 0.001) and inversely with TAS (r = −0.392, P < 0.001). After covariate adjustment, zonulin remained associated with IL-6 (B = 0.982, β = 0.577, P < 0.001), MDA (B = 36.76, β = 0.597, P < 0.001), and TAS (B = −0.018, β = −0.345, P = 0.021).

Conclusion

Serum zonulin was elevated in patients receiving maintenance HD and was independently associated with inflammatory and oxidative-stress biomarkers. These cross-sectional findings support an association but do not establish that altered intestinal permeability causes inflammatory-oxidative imbalance or that serum zonulin is ready for clinical use.