Soluble Toll-like Receptor 4: A New Player in Subclinical Inflammation and Malnutrition in Hemodialysis Patients

Abstract

Toll-like receptor 4 (TLR4) promotes inflammation in hemodialysis patients (HD). A soluble form of extracellular TLR4 (sTLR4) has been recently characterized, which showed the ability to attenuate TLR4 signalling. In this study, we describe the sTLR4 profile in regular HD patients. In a cross-sectional study we enrolled forty prevalent HD patients (68.2 ± 16.3 years, twenty-five males) with a median dialysis vintage of 41 months. Nineteen patients were undergoing standard bicarbonate HD (BHD) and 21 patients on-line hemodiafiltration (HDF). Ten healthy sex-matched subjects constituted the controls (C). Before and after the HD session, serum was tested for sTLR4 levels by ELISA. Moreover, clinical and biochemical datawere collected, including body mass index, albumin, and C-reactive protein (CRP) levels. Body composition was expressed as a 3-compartment model, providing lean tissue index and fat tissue index (FTI). Describe the profile of sTLR4 in HD patients, evaluating the correlations among sTLR4 levels and the main clinical characteristics, inflammatory and nutritional parameters. Patients with subclinical inflammation (i.e., high CRP levels without clinical symptomatology) presented higher sTLR4 levels (0.42±0.25ng/mL) with respect to both C and not inflamed HD patients (0.23±0.19ng/mL, P<.05). There was a significant direct correlation between predialysis sTLR4 and body mass index, FTI (r=0.55), and CRP levels (r=0.52) and inverse correlation with lean tissue index and albumin (r=-0.4). In multivariate analysis, sTLR4 resulted directly associated with FTI (P=.038). Notably, sTLR4 levels resulted higher in bicarbonate hemodialysis versus hemodiafiltration (0.37±0.18 vs. 0.19±0.21ng/mL, P<.05). sTLR4 correlates with inflammatory and nutritional parameters, presenting as a new potential player in modulating subclinical inflammation in HD patients.