Abstract Background and Aims The lifespan of erythrocytes in patients with renal anemia is shortened (∼70 days) compared to that of healthy erythrocytes (120 days), but the pathological mechanisms and causes are unclear. Senescent erythrocytes express phosphatidylserine (PS) on their outer membrane, which is a signal for being removed by macrophages. The PS localization in the cellular membrane is mainly regulated by two transporters: flippases and scramblases. Flippases, type Ⅳ P-type ATPases (P4-ATPases), maintain PS localization in the inner leaflet by transporting PS from the outer leaflet of the cell membrane. When scramblases are activated, they facilitate equal distribution of phospholipids between the inner and outer lipid bilayers, resulting in the exposure of PS on the outer leaflet. Recently, we have revealed that reduced flippase activity contributes to PS exposure in healthy senescent erythrocytes [1]. In this study, we examined the percentage of PS-exposed cells and the transporter activity in erythrocytes from renal anemia to elucidate the mechanism of the shortened lifespan. Method This study was approved by the Ethics Committee of Tokyo Women's Medical University (#3835, #4822R2). Erythrocytes from the renal anemic patients undergoing maintenance hemodialysis were separated with the centrifugation using Percoll-density gradient according to our previous report. Resultant heavy and light fractions were used as senescent and young erythrocytes, respectively. We analyzed the percentage of PS-exposed cells (n = 12), flippase/scramblase activities (n = 7), and the factors involved in those enzymatic activities such as intracellular K+ (n = 10) and ATP concentration (n = 9). We also measured protein 4.1a/b and HbA1c as an index of erythrocytes’ age. Results The cells from renal anemia were separated to heavy (senescent) and light (young) fractions, which was similar to the distributions previously performed on healthy erythrocytes. The PS-exposed erythrocytes in the heavy fraction were slightly more than those of the light fraction (p < 0.01, Wilcoxon test), and the flippase activity of the heavy fraction decreased more than that of the light fraction (p < 0.01, paired t-test). Intracellular K+ concentration decreased in the heavy fraction more than in the light fraction similar to the healthy senescent erythrocytes, but there was no statistical difference in the intracellular ATP concentration between the heavy and light fractions. The measurement of protein 4.1a/b and HbA1c in these fractions is still in progress. Conclusion Similar to healthy erythrocytes, reduced flippase activity contributes to PS exposure in senescent erythrocytes of renal anemia, maybe due to the decreased intracellular K+ concentration. This may occur in an earlier stage of senescence than the healthy ones, which may explain the mechanism of the shortened life span.