Red blood cell lifespan in long-term hemodialysis patients treated with roxadustat or recombinant human erythropoietin

Abstract

Introduction A significant decrease in red blood cell (RBC) survival has been observed in patients with renal failure, which is supposed to contribute to renal anemia. The aim of this observational study was to determine RBC survival in hemodialysis (HD) patients treated with roxadustat or recombinant human erythropoietin (rhuEPO) compared with healthy persons. Methods RBC lifespan was measured by Levitt’s CO breath test with newly developed automatic instrument ELS Tester. Results A total of 102 patients receiving long-term HD from two independent dialysis centers enrolled in the study, of whom 62 were treated with rhuEPO and 40 were on roxadustat therapy. A total of 25 healthy participants were recruited to match HD participants according to age and sex. Median RBC survival times in rhuEPO, roxadustat, and control groups were 65.0 (25th–75th percentile, 49.5–77.3), 75.5 (25th–75th percentile, 57.3–99.3), and 108.0 (25th–75th percentile, 89.0–141.5) d, respectively. Patients treated with roxadustat had significantly longer RBC survival time than patients treated with rhuEPO ( p < .05). In multivariate analysis of factors affecting RBC lifespan in the whole HD patients, anemia treatment drugs (rhuEPO/roxadustat) and levels of hemoglobin were the significantly independent factors. RBC survival was not found to correlate with either weekly rhuEPO dosage ( r = –0.087, p = .500) or weekly roxadustat dosage ( r = −0.267, p = .110) in our cohort. Conclusions HD patients treated with roxadustat had significantly longer RBC survival time than patients treated with rhuEPO, large prospective studies with long-term follow-up are warranted to verify the results in future. Abbreviations RBC: red blood cell; HD: hemodialysis; rhu EPO: recombinant human erythropoietin; ESRD: end-stage renal disease; EPO: erythropoietin; ROS: reactive oxygen species; CKD: chronic kideny disease; ESAs: erythropoiesis-stimulating agents; HIF-PHD: hypoxia-inducible factor prolyl hydroxylase; CO: carbon monoxide; Hb: hemoglobin

Effect of roxadustat on red blood cell lifespan in patients with long-term haemodialysis: a single-centre, prospective, single-arm study

“…In our recently published cross-sectional observational study, we found HD patients treated with roxadustat had longer RBC lifespans compared with patients treated with ESAs, indicating the effect of roxadustat on increasing RBC survival [ 10 ]. However, in that study, the shortest roxadustat treatment duration was only 3 months, and inferences drawn from observational studies may be subject to bias due to reverse causation.…”

“…RBC lifespan was measured using Levitt's carbon monoxide (CO) breath test by an electrophoretic light scattering (ELS) instrument (Seekya Biotec, Shenzhen, China) as described previously [ 10 ]. RBC lifespan values determined from the CO breath test using this instrument and the 15N-glycine labelling technique have been proved to be comparable, which suggested that the CO breath test is a reliable method for quickly determining human RBC lifespans in clinical applications [ 23 ].…”

“…Observations of the effect of ESAs on RBC lifespan are controversial [ 17–19 ]. In our recent measurements, RBC lifespan of haemodialysis (HD) patients treated with recombinant human erythropoietin (rhuEPO) maintaining haemoglobin (Hb) levels within target ranges remained at about half of the normal survival [ 10 ].…”

“…Roxadustat has been approved for treating renal anaemia in China, Japan, Korea and Europe. Our recent observational study demonstrated that maintenance HD patients treated with roxadustat had significantly longer RBC survival times than patients treated with rhuEPO, which indicated the possible efficacy of roxadustat in prolonging RBC lifespan [ 10 ]. We performed a 24-week, single-centre, single-arm study to further identify the effect of roxadustat on RBC survival in HD subjects.…”

Low Blood Glucose Index Associated with Cardiovascular Events in Diabetic Hemodialysis Patients

“…A population study has observed a close correlation between HbA1c and GMI [38] which was also observed in our results. Since it is recommended in all current guidelines as the chief biomarker for assessing long-term (2-3 months) glycemic control in dialysis patients depending on the lifespan of erythrocyte [39], patients with higher HbA1c levels with poor long-term blood glucose control may tend to have a higher possibility of short-term glycemic variability.…”