Background: Similar as in vascular endothelium the negatively charged glycocalyx of erythrocytes selectively buffers sodium. Loss of glycocalyx (i.e. loss of negative charges) leads to increased erythrocyte sodium sensitivity (ESS) quantified by a recently developed salt-blood-test (SBT). The hypothesis was tested whether a regular 4-hour hemodialysis (4h-HD) alters ESS. Methods:In 38 patients with end stage renal disease (ESRD) ESS was measured before and after 4h-HD, together with standard laboratory and clinical parameters (electrolytes, acid-base status, urea, creatinine, hemoglobin, c-reactive protein and blood pressure). Results: Before 4h-HD, 20 patients (out of 38) were classified as “salt sensitive” by SBT. After 4h-HD, this number decreased to 11. Erythrocyte sodium buffering power remained virtually constant in patients with already low ESS before dialysis, whereas in patients with high ESS, 4h-HD improved the initially poor sodium buffering power by about 20%. No significant correlations could be detected between standard blood parameters and the respective ESS values except for plasma sodium concentration which was found increased by 3.1 mM in patients with high salt sensitivity. Conclusions: 4h-HD apparently recharges “run-down” erythrocytes and thus restores erythrocyte sodium buffering capacity. Besides the advantage of efficient sodium buffering in blood, erythrocytes with sufficient amounts of free negative charges at the erythrocyte surface will cause less (mechanical) injury to the negatively charged endothelial surface due to efficient repulsive forces between blood and vessel wall. Hemodialysis improves erythrocyte surface properties and thus may prevent early vascular damage in patients suffering from ESRD.