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

Abstract

ObjectiveIn 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.Patients96 consecutive patients receiving regular HD were included. 20 adult patients without major renal, cardiovascular or metabolic morbidities served as controls.MethodsAS 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.ResultsPro-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.ConclusionsOur 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.

Cardiometabolic Effects of Irisin in Patients with End-Stage Renal Disease on Regular Hemo- or Peritoneal Dialysis

“…Oxidative and inflammatory stress may contribute to the predominance of the MAPK-ET-1 over PI3-K-Akt-NO pathway. It is of particularly relevant to patients receiving renal replacement therapy who encounter high levels of reactive oxygen species and pro-inflammatory molecules [29].…”

The aging venous system: from varicosities to vascular cognitive impairment

“…There is a strong connection between aging and chronic sterile inflammation in the cardiovascular system [10,25,27,28,217,[227][228][229][230][231]. The mechanisms contributing to age-related sterile vascular inflammation are likely multifaceted.…”

Tumour necrosis factor alpha (TNFα) and alpha-Klotho (αKL) in children and adolescents with chronic kidney disease (CKD)

“…Low levels of αKL protein were related to adverse cardiovascular outcomes, as examined by Sági et al in adult patients with CKD on haemodialysis, including 24% of patients dialyzed due to diabetic nephropathy. Depressed soluble Klotho levels were shown in those patients, but the authors failed to detect their association with vascular calcifications or confirm their relationship with inflammatory indices [28]. We also did not confirm the relationship of Klotho concentration with variables describing blood pressure (SBP, DBP, MAP).…”