ABSTRACT
End-stage renal disease (ESRD) presents a complex syndrome in which inflammatory and metabolic processes contribute to disease progression and development of comorbid conditions. Over $1 trillion is spent globally on ESRD care. Plasma samples collected from 83 ESRD patients prior to hemodialysis were profiled for metabolic and inflammatory biomarker concentrations. Concentrations were compared between groups with and without history of stroke, acute coronary syndrome (ACS), congestive heart failure (CHF), and coronary artery disease (CAD). The 25 patients (30.1%) with history of stroke demonstrated decreased plasma interferon-γ levels (p = 0.042) and elevated plasma resistin, interleukin (IL)-1α, and leptin levels (p = 0.008, 0.021, 0.026, respectively) when compared with ESRD patients without history of stroke. The 14 patients (16.9%) with history of ACS demonstrated elevated plasma IL-6 levels (p = 0.040) when compared with ESRD patients without history of ACS. The 30 patients (36.1%) with history of CHF demonstrated decreased plasma leptin levels (p = 0.031) and elevated plasma IL-1ß levels (p = 0.042) when compared with ESRD patients without history of CHF. Finally, the 39 patients (47.0%) with history of CAD demonstrated elevated plasma IL-1α levels (p = 0.049) when compared with ESRD patients without history of CAD. Plasma biomarker concentration disturbances were observed in ESRD patients with history of stroke, ACS, CHF, and CAD when compared with ESRD patients without such history. Proinflammatory biomarker elevations were seen in stroke, ACS, CHF and CAD, while adipocytokine aberrations were observed in both stroke and CHF. These studies demonstrate that biomarker profiling of vascular comorbidities in ESRD may provide useful diagnostic and prognostic information in the management of ESRD patients.
ABSTRACT
BACKGROUND: End stage renal disease (ESRD) is a debilitating disease that not only impacts quality of life, but also increases the risk of cardiovascular disease, stroke, and overall mortality. By improving our understanding of the molecular patterns seen in progression of chronic renal disease (CRD), we may be able to slow down and possibly even prevent progression renal failure. The vascular endothelial growth factor (VEGF) has been implicated as a major contributor to CRD disease progression, thus our aim was to profile the VEGF levels in patients with ESRD and to determine the effects of the erythropoietin stimulating agents (ESAs). METHODS: Under institution review board (IRB) approval, plasma samples were collected from 77 patients prior to hemodialysis and heparin administration. Normal human plasma samples (female & male, 18-35 years old) were purchased from George King Biomedical Inc (Overland Park, KS). All samples were stored at -80 °C. Inflammatory biochips were purchased from RANDOX (Co. Antrim, Northern Ireland) to test VEGF on 77 ESRD and 48 normal samples. RESULTS: The VEGF was significantly elevated in ESRD vs. normal (P<0.0001), ESRD+ESA vs. normal (P<0.0001), and ESRD-ESA vs. normal (P<0.0001). No difference was seen between ESRD+ESA and ESRD-ESA. Hemoglobin and free iron were significantly elevated in ESRD-ESA compared to ESRD+ESA (PHemoglobin=0.0007, PIron<0.0001). CONCLUSIONS: Our finding that VEGF was significantly elevated in ESRD vs. normal, aligns with the literature and suggests that VEGF may in fact play a key role in CRD progression. However, further studies to evaluate VEGF isomer levels are needed. While we saw lack of difference in VEGF levels between ESRD+ESA and ESRD-ESA, this may be due to the treatment algorithm used. Further investigation is warranted to determine whether the ESAs and hemoglobin levels show any influence on or crosstalk with the VEGF levels.
