Blood modifications associated with end stage renal disease duration, progression and cardiovascular mortality: a 3-year follow-up pilot study

• Cardiovascular mortality in ESRD is reflected in novel blood and RBC modifications.
• Mortality risk is linked to damaged RBCs, bad tolerance and poor response to HD.
• Membrane protein changes include oxidative and cell volume/hydration defects.
• ESRD duration significantly contributes to additional remodeling of the membrane.
• Novel RBC compensatory responses to the chronic uremic stress are detected.

Chronic kidney disease is a risk factor for cardiovascular mortality. This study uncovers pieces of hematological and erythrocyte protein variability observed in end stage renal disease (ESRD) in relation to disease progression/duration and mortality. Using a variety of experimental approaches, erythropoietin/dialysis-treated patients were compared to healthy individuals and had been followed for 36 months. During that period, half of the patients died from cardiovascular diseases. The high levels of uremic toxins in those patients were associated with damaged erythrocytes, bad tolerance and poor response to hemodialysis therapy. The postmortem study revealed significant variation in alkaline phosphatase, duration of dialysis, erythrocyte transformation and intracellular hemoglobin concentration compared to the survived patients. The erythrocyte proteins showed substantial remodeling characteristic of pathologic regulation of cell hydration and susceptibility to the dialysis-induced oxidation defects. According to the follow-up study, duration of hemodialysis was associated with a trend towards increased intracellular hemoglobin concentration, membrane expression of glucose transporter-1 and stomatin as well as lower levels of circulating stomatocytes. The uremic index variation in long survived patients is accurately reflected in plasma and erythrocyte oxidative stress modifications. The ESRD patients exhibit impressive compensatory responses to the chronic challenges of the uremic milieu.Biological significanceThis study demonstrates novel blood modifications probably associated with the duration of erythropoietin/hemodialysis treatment, disease progression and cardiovascular mortality in end stage renal disease. The observed variability adds new pieces to the erythrocyte pathophysiology puzzle in end stage renal disease and suggests novel hematologic and proteomic factors for consideration in future large scale studies on cardiovascular morbidity and mortality candidate biomarkers in uremic patients.

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