Correlation between Inflammatory Biomarkers and Red Blood Cell Life Span in Chronic Hemodialysis Patients

Abstract

Background and Objectives: The pathogenesis of anemia in hemodialysis (HD) patients is dependent on multiple factors, with decreased red blood cell life span (RBCLS) being a significant contributor. Although the impact of reduced RBCLS on anemia is recognized, it is still a subject that is not well researched. The objective of this study was to investigate the relationship between RBCLS and inflammatory biomarkers in chronic HD patients. Design, Setting, Participants, and Measurements: RBCLS was calculated from alveolar carbon monoxide concentrations measured by gas chromatography. Interleukins (IL) IL-6, IL-18, IL-10, and high sensitivity C-reactive protein were measured using bead-based multiplex assay. Measurements were carried out at baseline and during follow-up. The associations between RBCLS and inflammatory biomarkers were evaluated using linear mixed effects models. Results: RBCLS measurements were available for 54 HD patients. Their average age was 58.5 ± 14.4 years, 68.5% were males, 48.1% were diabetics, and the HD vintage was 51 ± 48 months. In 4 patients, RBCLS was measured once, while in 50 patients, up to 5 repeated RBCLS measurements were available. RBCLS was 73.2 ± 17.8 days (range 37.7-115.8 days). No association was found between RBCLS and any of the inflammatory biomarkers. Of note, RBCLS was positively correlated with levels of uric acid (p = 0.02) and blood urea nitrogen (BUN; p = 0.01), respectively. Conclusion: Our study suggests that inflammation pathways reported by these biomarkers only have a limited role in causing premature RBC death. The positive correlation with uric acid and BUN warrants further studies.

Recipient's effects on stored red blood cell performance: the case of uremic plasma

“…The high antioxidant capacity of uremic plasma, which is mainly UA‐based, may further benefit the recovery of donor RBCs. Serum UA levels that are positively correlated with the RBC life span in chronic HD patients affect storage lesion metrics in RBCs under several storage strategies . This study further extends the influential central position of UA in the transfusion context by including a recipient‐related aspect.…”

Donor‐specific individuality of red blood cell performance during storage is partly a function of serum uric acid levels

“…Such a protective role of UA has been also shown in platelet (PLT) concentrates where addition of urate in excess leads to lower ROS production . Moreover, the UA present in the uremic plasma exerts a strong antioxidant effect compared to healthy plasma on both healthy RBCs and RBCs from subjects with severe renal disease in vitro, while its levels can effectively predict the RBC life span in chronic hemodialysis patients …”

“…17 Moreover, the UA present in the uremic plasma exerts a strong antioxidant effect compared to healthy plasma on both healthy RBCs and RBCs from subjects with severe renal disease in vitro, 18 while its levels can effectively predict the RBC life span in chronic hemodialysis patients. 19 Further end-of-storage diversification of the blood units, in favor of the high-UA ones, include the interrelated variables of intracellular calcium accumulation and severe shape modifications that can be also associated with a better antioxidant capacity. 20 Of note, those cells produce proportionally less EVs in the size range of 100 to 300 nm that are characteristic of the Hb-containing exovesicles released in nonleukoreduced CPDA-1 units (microvesicles/microparticles with mean sizes of 137-160 nm), as previously shown by immune-electron microscopy.…”

Short-term effects of hemodiafiltration versus conventional hemodialysis on erythrocyte performance

“…Nevertheless, apart from being a uremic toxin, the end product of purine metabolism in human is a potent natural antioxidant factor, that protects both plasma (in the antioxidant capacity of which it contributes by 35-65%) and cells from oxidative damages, through its free radical scavenging capacity (Assis et al 2015; Tzounakas et al 2015). Of note, either as an indicator of better nutritional status or not, low UA has been proposed as a mortality risk factor in HD patients (Beberashvili et al 2015) and more recently, it was found that RBC life span (that is a significant measure of/contributor to anemia) in dialysis patients is positively correlated with levels of uric acid and blood urea nitrogen (Ma et al 2017). The high clearance D r a f t potential of HDF probably results in the acute elimination of additional dilute factors that also function in strengthening the antioxidant defense reactions in plasma, including albumin (Ahrenholz et al 2004), vitamins (Morena et al 2002) and trace elements (Prodanchuk et al 2014).…”