Different translational activities of inflammatory regulators associated with hypervolemia in haemodialysis patients

Abstract

The inflammatory burden in chronic kidney disease patients under maintenance haemodialysis (HD) is high. Overhydration (hypervolemia) associates closely with inflammation in HD, while its patho-mechanisms are still elusive. Anti-inflammatory mediators such as IL-10 and TIPE2, as well as anti-inflammatory regulators such as OTUD1, are key controllers of cellular homeostasis after chronic inflammatory insults. Forty-two HD patients and nine healthy controls (CO) were enrolled in a cross-sectional pilot study. Bioimpedance measurements were performed to dichotomise the HD patients into a normovolemic (N) and a hypervolemic (H) group. Polysome profiling (inclusive monosomal, early and late polysomal peak analysis) followed by translational activity analysis of IL-10, TIPE2 and OTUD1 were performed. mRNA expression and translational activity of IL-10 were neither different between N and H nor between HD and CO. Significantly higher TIPE2 mRNA expression in PBMCs was measured in H versus CO, whereas translational activity failed to be different in the three cohorts at all. In contrast, monosomal translational activity of OTUD1 was significantly different when H vs. N and H vs. CO were compared. Inflammation is insufficiently balanced in chronic kidney disease, as the translational activity of the anti-inflammatory mediators IL-10 and TIPE2 are not different either between N and H or between HD and CO. The deubiquitinase OTUD1 appears to be significantly upregulated in hypervolemia. As not only TIPE2 but also different other molecules are target of OTUD1, the exact mechanistic interaction between OTUD1 and TIPE2 in HD must be evaluated.