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

Figures & data

Table 1. General characteristics of the study HD participants.

Variable	rhuEPO	Roxadustat
	At the RBC lifespan measurement n = 62	Before the use of roxadustat n = 35	At the RBC lifespan measurement n = 40
Age (mean ± SD) (years)	57.0 ± 13.4	52.4 ± 13.0	53.9 ± 13.3
Sex (male/female)	38/24	23/17	23/17
Cause of ESRD
Diabetes (%)	18 (29.0)	13 (32.5)	13 (32.5)
Hypertension (%)	4 (6.5)	1 (2.5)	1 (2.5)
Glomerulonephritis (%)	26 (41.9)	18 (45.0)	18 (45.0)
Polycystic disease (%)	2 (3.2)	0 (0)	0 (0)
Other (HSPN, unknown) (%)	12 (19.6)	8 (20%)	8 (20%)
HD vintage (mean ± SD) (months)	51.9 ± 41.2	41.1 ± 35.6	42.6 ± 37.2
Weekly HD hours (mean ± SD)	11.7 ± 1.0	11.5 ± 1.3	11.5 ± 1.3
Single-pool Kt/V	1.25 ± 0.17	1.22 ± 0.23	1.23 ± 0.21
Residual urine volume (median, range) (ml)	100 (0, 1200)	100 (0, 1000)	100 (0, 1000)
Weekly rhuEPO dose (mean ± SD) (U)	10,004 ± 3749	9500 ± 3794.3
Weekly roxadustat dose (mean ± SD) (mg)			297 ± 123
Roxadustat duration time (median, range) (month)			6 (3 ∼ 12)
Intravenous iron supplementation (%)	40 (64.5)	24 (68.6%)	15 (37.5)**
Hemoglobin (mean ± SD) (g/L)	112.0 ± 12.9	107.3 ± 29.6	116.1 ± 14.5
Reticulocyte ratio (mean ± SD) (%)	1.94 ± 0.81		1.90 ± 0.93
WBC (mean ± SD) (10^9/L)	5.95 ± 1.83	6.78 ± 1.87	6.19 ± 1.90
PLT (mean ± SD) (10^9/L)	177.8 ± 45.5	176.9 ± 58.4	187.7 ± 58.1
SCR (mean ± SD) (μmol/L)	875.8 ± 264.7	824.1 ± 148.6	846.5 ± 205.9
BUN (mean ± SD) (μmol/L)	25.8 ± 7.6	25.1 ± 4.2	29.1 ± 6.3
β2-MG (mean ± SD) (mg/L)	27.9 ± 4.1	23.7 ± 3.0***	23.7 ± 7.8**
ALB (mean ± SD) (g/L)	41.2 ± 4.4	39.7 ± 3.1	40.7 ± 4.8
Ca (mean ± SD) (mmol/L)	2.27 ± 0.22	2.33 ± 0.18	2.23 ± 0.21
P (mean ± SD) (mmol/L)	1.89 ± 0.56	1.99 ± 0.38	2.00 ± 0.51
Bicarbonate (mean ± SD) (mmol/L)	20.4 ± 4.0	21.6 ± 1.71	19.4 ± 2.8
Ferritin (mean ± SD) (μg/L)	318.3 ± 170.3	341.3 ± 186.8	168.8 ± 138.3***
Serum iron (mean ± SD) (μmol/L)	14.4 ± 4.8	14.2 ± 3.7	14.5 ± 4.6
TIBC (mean ± SD) (μmol/L)	44.0 ± 5.6	47.8 ± 6.7	53.2 ± 9.5***
Transferrin saturation (mean ± SD) (%)	33.3 ± 11.7	29.6 ± 10.0	27.6 ± 8.4
PTH (mean ± SD) (pg/mL)	335.1 ± 217.4	349.9 ± 348.5	280.2 ± 280.6
CRP (mean ± SD) (mg/L)	6.64 ± 17.1	1.85 ± 1.37	3.02 ± 4.12
Serum EPO levels (mean ± SD) (mIU/mL)	20.22 ± 33.20		19.19 ± 37.33
Serum folate levels (mean ± SD) (ng/mL)	7.94 ± 4.11		8.38 ± 4.65
Serum vitamin B12 levels (mean ± SD) (pg/mL)	589.61 ± 447.38		659.67 ± 534.31

SD: standard deviation; HSPN: Henoch–Schonlein syndrome; HD: hemodialysis; WBC: white blood cells; PLT: platelets; SCR: serum creatinine; BUN: blood urea nitrogen; β2-MG: β2 microglobulin; ALB: albumin; Ca: calcium; P: phosphate; TIBC: total iron-binding capacity; PTH: parathyroid hormone; CRP: C-reactive protein; EPO: erythropoietin

Data are provided as median (range) or mean (SD).

**p < .01 and ***p < .001, compared with the rhuEPO group with Dunnett’s test for multiple comparison correction.

Figure 1. Scatter plot shows red blood cell (RBC) survival in days in hemodialysis (HD) patients treated with rhuEPO or roxadustat, and controls. Group median values are represented by a full red horizontal line. For comparison RBC lifespan among the three groups, Kruskal–Wallis test was used with Bonferroni correction for multiple comparisons. *p < .05, ***p < .001, and ^**** p < .0001.

Figure 2. Relationship between RBC lifespan and hemoglobin (Hb). A significant positive correlation was observed between the RBC lifespan and Hb levels in 102 hemodialysis patients in a univariate linear correlation analysis (r = 0.256, p = .009).

Figure 3. Relationship between RBC lifespan and serum phosphate levels. A significant positive correlation was observed between the RBC lifespan and phosphate levels in 102 hemodialysis patients in a univariate linear correlation analysis (r = 0.205, p = .046).

Table 2. Univariate linear regression analysis of factors affecting the RBC lifespan.

	Non-standardized coefficients		Standardized coefficient Beta	t	p
	B	Standard error
Sex
Male	0 (reference)
Female	9.395	5.334	0.173	1.761	.081
Age (year)	−0.189	0.199	−0.095	−0.953	.343
HD vintage (month)	−0.093	0.066	−0.139	−1.399	.165
Weekly HD hours (hour)	−1.807	2.344	−0.077	−0.774	.440
Hemoglobin (g/L)	0.503	0.190	0.256	2.652	.009
Reticulocyte ratio (%)	−3.617	3.192	−0.125	−1.133	.260
SCR (μmol/L)	0.005	0.011	0.041	0.399	.691
BUN (mmol/L)	0.555	0.377	0.151	1.475	.143
β2-MG (mg/L)	−0.394	0.486	−0.089	−0.810	.421
ALB (g/L)	−0.548	0.617	−0.093	−0.888	.377
Ca (mmol/L)	16.380	12.672	0.133	1.293	.199
P (mmol/L)	10.232	5.053	0.205	2.025	.046
Bicarbonate (mmol/L)	−0.593	0.789	−0.079	−0.752	.454
Ferritin (μg/L)	0.006	0.016	0.040	0.373	.710
Transferrin saturation (%)	0.022	0.382	0.008	0.057	.955
PTH (pg/mL)	0.001	0.011	0.010	0.097	.923
Iron supplement dose (mg/month)	−0.025	0.027	−0.091	−0.918	.361
CRP (mg/L)	−0.341	0.279	−0.166	−1.224	.226
Residual urine volume (mL)	0.005	0.010	0.045	0.442	.659
Anti-anemia drug
rhuEPO	0 (reference)
Roxadustat	16.474	5.184	0.303	3.178	.002
Diabetes
Without diabetes	0 (reference)
With Diabetes	−1.683	5.721	−0.029	−0.294	.769

HD: hemodialysis; SCR: serum creatinine; BUN: blood urea nitrogen; β2-MG: β2 microglobulin; ALB: albumin; Ca: calcium; P: phosphate; PTH: parathyroid hormone; CRP: C-reactive protein

Table 3. Multiple linear regression analysis of factors affecting the RBC lifespan.

	Non-standardized coefficients		Standardized coefficient Beta	t	p
	B	Standard error
Constant	2.593	23.348		0.111	.942
Anti-anemia drug
rhuEPO	0 (reference)				–
roxadustat	12.977	5.321	0.239	2.439	.017
Hemoglobin (g/L)	0.409	0.197	0.204	2.080	.040
Phosphate (mmol/L)	8.019	4.839	0.161	1.657	.101