Forty-three patients were enrolled in April 2018, fulfilling the inclusion/exclusion criteria and providing informed consent. Twenty-one patients were assigned to start HDx therapy and 22 to stay on HDF therapy. Baseline demographics were similar between the two study arms (table 1).
Table 1: Patient demographics at study baseline
|
HDx study arm
(N = 21)
|
HDF study arm
(N=22)
|
Age (y)
|
60.7 ± 14.3
|
61.8 ± 9.4
|
Gender (% males)
|
57%
|
73%
|
Body weight (kg)
|
76.6 ± 13.1
|
75.9 ± 16.0
|
Dialysis vintage (months)
|
58 ± 59
|
60 ± 78
|
Urine production
|
|
|
Anuric (<100 ml/24h)
|
48%
|
45%
|
Oliguric (100-500 ml/24h)
|
29%
|
32%
|
Non-oliguric (>500 ml/24h)
|
23%
|
23%
|
ESRD comorbidity index
|
2.5 ± 1.7
|
1.9 ± 1.8
|
Malnutrition Inflammation Score
|
3.4 ± 2.1
|
3.5 ± 1.4
|
Acceptance to the HDx therapy was high in those patients who switched from HDF to HDx. One patient in the HDF arm died during the study. Two patients were excluded due to severe adverse events not related to dialysis, one in each study arm. In addition, nine patients were discontinued from the study as they left the study unit going on vacation for more than two weeks. Most of these left after the week 12 assessment and, by chance, most were in the HDF study arm. The patient flow is summarized in Supplementary figure 1.
Treatment characteristics are reported in table 2. Mean blood flow rate during the study was close to 400 mL/min in both groups over time. Treatment duration was 4 hours. HDF treatments showed a substitution volume that averaged 24 liters. With 2.4 liters of mean UF volume the mean total convective volume was close to 26 liters.
Table 2: Study treatment characteristics at week 12
|
HDx
(N = 21)
|
HDF
(N=19)
|
Treatment duration (min)
|
241 ± 4
|
239 ± 7
|
Blood flow rate (mL/min)
|
400 ± 12
|
396 ± 8
|
Dialysis fluid flow rate (mL/min)
|
500
|
600
|
Ultrafiltration volume (L)
|
2.5 ± 0.8
|
2.1 ± 0.8
|
Substitution fluid volume (L)
|
n.a.
|
24.4 ± 3.2
|
n.a. = not applicable
Intra-dialytic changes in biomarker levels
Pre- to post-dialysis RR for MMs was greater in the HDx study arm for YKL-40 (58.1 ± 9.5 vs 42.4 ± 12.5 %; p<0.0001) while it appeared similar between HDx and HDF for β2m (76.6 ± 5.6 vs 77.2 ± 5.6 %; p=0.47) and FGF-23 (48.1 ± 21.3 vs 45.1 ± 20.8 %; p=0.63). For FLC, measured by the N Latex assay, the RRs were also similar between therapies for kappa FLC (67.0 ± 5.9 vs 64.9 ± 6.9 %; p=0.40) and lambda FLC (67.7 ± 6.2 vs 65.9 ± 8.2 %; p=0.31) – see figure 1.
The HDx and HDF study arms showed similar percent change from pre- to post-dialysis for inflammatory biomarkers: IL-6 (-13.7 ± 13.2 vs -16.9 ± 14.7 %; p=0.29), CRP (-7.2 ± 12.1 vs -8.8 ± 10.6 %; p=0.62), and PTX3 (+5.2 ± 24.9 vs +8.6 ± 30.5 %; p=0.45).
Both study arms showed a mean delivered spKt/V of 1.8, ranging between subjects from 1.3 to 2.6.
Biomarker changes over time
Pre-dialysis levels of β2m, FGF-23, FLCs, and YKL-40 were similar between study arms at baseline and their changes to 12 and 24 weeks did not differ between arms except for borderline differences at week 24 for β2m (p=0.045) and FGF-23 (p=0.039); see table 3. Inflammatory markers CRP, IL-6, and PTX3 were also similar between groups at baseline, and changes over the 24-week study period appeared insignificant and similar between study arms. Likewise, changes over time in plasma levels of albumin, fibrinogen, hemoglobin, PTH, and phosphate did not differ between study arms (table 3).
Table 3
Baseline pre-dialysis levels and changes from baseline for the studied biomarkers
|
|
baseline
|
Change to
week 12
|
Change to
week 24
|
B2m (mg/L)
|
HDx
|
25.4 ± 7.6
|
−0.6 ± 3.6
|
−0.6 ± 3.9
|
HDF
|
24.3 ± 7.5
|
−1.0 ± 4.5
|
+ 3.3 ± 6.1
|
p-value
|
0.62
|
0.55
|
0.046
|
FGF-23 (pg/mL)
|
HDx
|
1153 (402, 1979)
|
−20 (−597, + 512)
|
−24 (−623, + 202)
|
HDF
|
825 (277, 1438)
|
+ 208 (−537, + 494)
|
+ 343 (+ 44, + 1152)
|
p-value
|
0.28
|
0.45
|
0.039
|
YKL-40 (ng/mL)
|
HDx
|
432 ± 325
|
+ 2 ± 114
|
0 ± 132
|
HDF
|
507 ± 491
|
−3 ± 234
|
+ 103 ± 432
|
p-value
|
0.56
|
0.94
|
0.16
|
Kappa FLC (mg/L)
|
HDx
|
143 ± 41
|
−5 ± 17
|
+ 7 ± 35
|
HDF
|
151 ± 45
|
−4 ± 30
|
+ 20 ± 46
|
p-value
|
0.52
|
0.75
|
0.56
|
Lambda FLC (mg/L)
|
HDx
|
129 ± 37
|
−3 ± 28
|
+ 19 ± 37
|
HDF
|
173 ± 141
|
8 ± 43
|
+ 44 ± 58
|
p-value
|
0.17
|
0.65
|
0.28
|
IL-6 (pg/mL)
|
HDx
|
8.6 ± 5.3
|
−0.3 ± 2.6
|
−0.5 ± 2.2
|
HDF
|
7.2 ± 3.2
|
−0.1 ± 3.1
|
−0.1 ± 2.3
|
p-value
|
0.32
|
0.83
|
0.49
|
CRP (mg/L)
|
HDx
|
2.4 (1.3, 4.7)
|
−0.3 (−1.0, + 0.3)
|
0.0 (−0.7, + 1.1)
|
HDF
|
5.6 (2.6, 8.4)
|
−0.7 (−4.0, + 0.1)
|
−0.4 (−1.6, + 4.2)
|
p-value
|
0.18
|
0.34
|
0.68
|
PTX-3 (pg/mL)
|
HDx
|
4.8 ± 2.7
|
+ 0.6 ± 2.1
|
0.0 ± 1.8
|
HDF
|
6.8 ± 4.8
|
−0.9 ± 2.4
|
−1.0 ± 3.9
|
p-value
|
0.10
|
0.39
|
0.75
|
Albumin (g/dL)
|
HDx
|
3.67 ± 0.38
|
+ 0.06 ± 0.46
|
−0.02 ± 0.25
|
HDF
|
3.78 ± 0.32
|
−0.01 ± 0.26
|
−0.02 ± 0.34
|
p-value
|
0.33
|
0.89
|
0.59
|
Fibrinogen (mg/dL)
|
HDx
|
352 ± 95
|
−45 ± 75
|
−22 ± 74
|
HDF
|
376 ± 126
|
−72 ± 117
|
−94 ± 103
|
p-value
|
0.49
|
0.78
|
0.13
|
Hemoglobin (g/dL)
|
HDx
|
11.3 ± 0.8
|
+ 0.3 ± 1.2
|
−0.2 ± 1.0
|
HDF
|
11.4 ± 0.8
|
−0.3 ± 1.1
|
+ 0.1 ± 1.0
|
p-value
|
0.69
|
0.19
|
0.16
|
PTH (pg/mL)
|
HDx
|
413 ± 214
|
+ 36 ± 328
|
+ 51 ± 330
|
HDF
|
309 ± 181
|
+ 34 ± 191
|
+ 210 ± 293
|
p-value
|
0.09
|
0.66
|
0.30
|
Phosphorous (mg/dL)
|
HDx
|
4.25 ± 1.11
|
+ 0.04 ± 1.54
|
+ 0.17 ± 1.16
|
HDF
|
3.79 ± 0.68
|
+ 0.36 ± 0.96
|
+ 0.67 ± 0.76
|
p-value
|
0.11
|
0.87
|
0.67
|
Data presented as mean ± SD or as median (25th, 75th percentile) |
Exploratory – anemia management
All subjects in the HDF study arm and 20 out of 21 subjects in the HDx study arm received ESA during the study. Thirty-one subjects received erythropoietin (HDF: 17; HDx:14) while 9 received darbepoetin alpha (HDF: 3; HDx:6); in addition, 2 patients in the HDF arm were on darbepoetin alpha at the start of the study but shifted to erythropoietin during the study. When evaluating subjects who completed the 24-week study period, those in the HDF study arm (N=12) showed stable mean weekly dose of ESA over time (baseline: 99 ± 74 IU/kg, week 12: 113 ± 75 IU/kg, week 24: 102 ± 74 IU/kg) while the HDx study arm subjects (N=19) showed a trend towards a decrease in weekly ESA dose from week 8 (baseline: 106 ± 87 IU/kg, week 12: 98 ± 102 IU/kg, week 24: 77 ± 103 IU/kg) (figure 2A). ERI in ESA-treated patients showed a similar trend without significant difference between groups (figure 2B) while hemoglobin level appeared stable over time in both groups (figure 2C). The use of intravenous iron did not differ significantly between treatment arms, although with a trend of reduced need over time in the HDx arm. Transferrin saturation and ferritin levels were comparable at baseline (23.1 ± 7.8 % and 297 ± 275 ng/mL for HDx arm vs. 20.8 ± 7.4 % and 231 ± 201 ng/mL for HDF arm) and changes during the study period were similar between groups.
Adverse events
Overall, a total of 37 subjects (86%) were reported to experience 134 adverse events (AEs, serious or nonserious) during the study; 18 subjects with 79 AEs in the HDx group and 19 subjects with 55 AEs in the HDF group. Hypotension, muscle cramps, and hypertension were the most reported AEs. Intradialytic hypotension episodes were not seen in any patient during the study period. Eight AEs were rated as serious (3 in HDx, 5 in HDF); none of these were judged to be related to the dialysis procedure.