Abstract: FR-PO788

Increased Levels of Extracellular Nucleosomes, Biomarkers of Cell Death, in Stage 5 Chronic Kidney Hemodialysis (CKD5-HD) Are Independent of Circulating Tissue Factor Microparticle Complex

Session Information

Category: Dialysis

  • 601 Standard Hemodialysis for ESRD

Authors

  • Bansal, Vinod K., Loyola University Medical Center, Maywood, Illinois, United States
  • Phan, Trung, Loyola University Medical Center, Maywood, Illinois, United States
  • Mcmillan, Ryan, Loyola University Medical Center, Maywood, Illinois, United States
  • Walborn, Amanda, Loyola University Medical Center, Maywood, IL, Illinois, United States
  • Hoppensteadt, Debra, Loyola University Medical Center, Maywood, Illinois, United States
  • Fareed, Jawed, Loyola University Medical Center, Maywood, Illinois, United States
Background

Extracellular nucleosomes in plasma (PNs) are complexes of DNA and histones that are released during cell death. In both the chronic and acute kidney injury, there is an increased release of nucleosomes with decreased nucleosome clearance. Nucleosomes mediate inflammatory and thrombotic responses and could serve as biomarkers in chronic kidney diseases. Microparticle-associated tissue factor (MP-TF) are released during cell death and mediate thrombotic responses.

Methods

Plasma levels of PNs in CKD5-HD patients (n = 90) and healthy volunteers (n = 50) were measured using the Cell Death Detection ELISA PLUS assay (Roche Diagnostics, Mannheim, Germany). MP-TF levels were measured using the ZYMUPHEN MP-TF kit (Hyphen BioMed, Neuville-sur-Oise, France). The levels of both PNs and MP-TF were also correlated with WBCs, RBCs and platelets to determine the origin of measured PNs.

Results

In comparison to the plasma from healthy volunteers (6.74 ± 13.7 Arbitrary Units (AU)), the levels of PNs in CKD5-HD patients were higher (15.5 ± 14.1 AU; p < 0.0001). Similarly, MP-TF levels were elevated in CKD5-HD patients (3.00 ± 1.42 pg/mL; p < 0.0001) compared to normal (0.363 ± 0.263 pg/mL). There was no correlation between PNs and MP-TF in CKD5-HD patients (r = 0.077; p = 0.501). Moreover, there was no correlation between PNs and platelets (r = 0.067; p = 0.543) and RBCs (r = 0.083; p = 0.447). However, the PNs showed a positive correlation with WBCs (r = 0.223; p = 0.042). There was no correlation between MP-TF and WBCs (r = -0.057; p = 0.632) and RBCs (r = -0.042; p = 0.722), but a positive correlation was observed between MP-TF and platelets (r = 0.237; p = 0.042).

Conclusion

PNs were elevated in CKD5-HD patients, indicating an increased release of nucleosomes, suggesting increased cell death. The observed correlation between PNs and WBCs suggests that the detected PNs are derived from WBCs. A lack of correlation between PNs and MP-TF suggests that the MP-TF increase is independent of the pathophysiologic processes responsible for abnormal PN generation in CKD5-HD patients.