Pro- and anti-inflammatory factors, vascular stiffness and outcomes in chronic hemodialysis patients.

Abstract

Objective In this observational study we addressed accelerated arteriosclerosis (AS) in patients with chronic renal failure (CRF) on hemodialysis (HD) by measuring vascular stiffness (VS) parameters and attempted to relate them to pro-inflammatory and protective factors. Patients 96 consecutive patients receiving regular HD were included. 20 adult patients without major renal, cardiovascular or metabolic morbidities served as controls. Methods AS parameters (carotid-femoral pulse wave velocity - PWV, aortic augmentation index - Aix) were measured by using applanation tonometry (SphygmoCor, AtCor Medical, Sidney). In addition to routine laboratory tests 25(OH) vitamin D3 (vitamin D3) and high-sensitivity C-reactive protein (hsCRP) were quantified by immunometric assay; whereas fetuin-A, α-Klotho, tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) were determined by ELISA. Results Pro-inflammatory biomarkers (hsCRP, TNF-α and TGF-β1) were markedly elevated (P < 0.01), while anti-inflammatory factors (fetuin-A: P < 0.05, α-Klotho: P < 0.01, vitamin D3: P < 0.01) significantly depressed in HD patients when compared to controls. PWV was significantly affected only by total cholesterol, fetuin-A and dialysis time. Multiple linear regression analyses revealed that several clinical and laboratory parameters were associated with pro- and anti-inflammatory biomarkers rather than VS. The impact of baseline clinical and biochemical variables on outcome measures were also analyzed after three-year follow-up, and it was demonstrated that low levels of vitamin D, α-Klotho protein and fetuin-A were related to adverse cardiovascular outcomes, whereas all-cause mortality was associated with elevated hsCRP and depressed vitamin D. Conclusions Our results provide additional information on the pathomechanism of accelerated AS in patients with CRF, and documented direct influence of pro- and anti-inflammatory biomarkers on major outcome measures.