Effect of erythropoietin stimulating agents on vascular endothelial growth factor levels in patients with end stage renal disease.

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.

Prevalence of metabolic syndrome in patients with end stage renal disease and relevance of biomarkers.

BACKGROUND: As chronic kidney disease (CKD) and metabolic syndrome (MetS) share many of the same risk factors and similar inflammatory pathogenesis, multiple studies have suggested a correlation between CKD and MetS.. The purpose of this study is to investigate the prevalence of MetS in end stage renal disease (ESRD) patients. Furthermore, investigating metabolic biomarker levels in patients with ESRD may provide insight into the pathogenic processes and the development of associated comorbidities. METHODS: Under IRB approval, plasma samples were collected from 89 patients with ESRD prior to hemodialysis. Biochips purchased from RANDOX (Co. Antrim, Northern Ireland) were used to test C peptide, ferritin, IL-6, resistin, insulin, TNFα, IL-1α, leptin, PAI-1 on 82 ESRD and 17 normal samples. RESULTS: All biomarkers, except insulin, were significantly elevated in patients with ESRD, suggesting an ongoing inflammatory process. Patients with ESRD+MetS, as compared to ESRD-MetS, had significantly elevated leptin. Furthermore, ESRD+MetS vs. normal was significant for leptin, but ESRD-MetS vs. normal was not. ESRD+MetS and ESRD-MetS populations were not statistically different for all other biomarkers. CONCLUSION: These findings suggest elevated Leptin in ESRD may be attributed to MetS, which is highly prevalent in the ESRD population, rather than ESRD/CKD pathogenesis alone. Lack of a significant difference for all other biomarkers suggest biomarker elevation is due to ESRD pathogenesis, rather than due to MetS as a comorbidity.