Eryptosis in Patients with Chronic Kidney Disease: A Possible Relationship with Oxidative Stress and Inflammatory Markers

Abstract

Background. Eryptosis is the programmed death of red blood cells; it may contribute to worsening anemia in chronic kidney disease (CKD). In this clinical condition, different factors induce eryptosis, such as oxidative stress, energy depletion and uremic toxins. In our study, we investigated if the progression of CKD may influence erythrocyte death levels and its relationship with oxidative stress and inflammation. Methods. We evaluated eryptosis levels in 25 CKD patients (five for each stage), as well as markers of oxidative stress and inflammation: myeloperoxidase (MPO), copper/zinc superoxide dismutase (Cu/Zn SOD) and interleukin-6 (IL-6) were evaluated in plasma samples. Results. Higher cell death rate was reported in the highest CKD stages (p < 0.05). Furthermore, we divided CKD patients into two groups (eGFR< or ≥60 mL/min/1.73 m2). Patients with eGFR < 60 mL/min/1.73 m2 had higher eryptosis levels (p < 0.001). MPO, CU/Zn SOD and IL-6 resulted significantly differently between groups (p < 0.001). Significant positive correlations were reported between eryptosis and MPO (Spearman’s rho = 0.77, p = 0.01) and IL-6 (Spearman’s rho = 0.52, p = 0.05) and Cu/Zn SOD. Spearman’s rho = 0.6, p = 0.03). Conclusions. In patients with CKD, different factors are involved in the pathogenesis of eryptosis, in particular uremic toxins and oxidative stress and inflammatory markers. The progressive impairment of renal function may be associated with the increase in eryptosis levels, probably due to the accumulation of oxidative stress factors, inflammatory cytokines and uremic toxins.

Molecular Mechanisms and Pathophysiological Significance of Eryptosis

“…Patients in the later stages of chronic renal impairment (stages G4 and G5) have greater eryptosis levels than those in the earlier stages of the illness (stage G1, G2 and G3) [ 99 ]. Erythrocytosis in chronic renal illness can be affected by a number of factors [ 100 ], including oxidative stress, energy loss, and uremic toxins.…”

“…All these factors contribute to an increased rate of RBC mortality, and they all rise alongside a decline in renal function. Increased eryptosis has been linked to uremic toxins in patients with chronic renal disease [ 99 ]. Phosphatidylserine (PS) is exposed on the surface of RBCs because indoxyl sulfate raises the cytosolic calcium concentration and stimulates erythrocyte cell membrane scrambling [ 101 ].…”

“…In addition, vanadate has been shown to cause eryptosis by blocking ATP synthesis, thus producing an energy-deficient condition in individuals with chronic renal disease [ 99 ]. Recent research has shown that uremic toxins, including urea and p-cresol, are cytotoxic to healthy RBCs.…”

“…A lower glomerular filtration rate and a longer time spent on dialysis are both associated with higher levels of oxidative stress. As a result of aging, diabetes, hypertension, and dyslipidemia, as well as the suppression of antioxidant systems (lower levels of vitamin C and glutatione), oxidative stress is increased in end-stage renal disease [ 99 ].…”