Supplemental Figure 1. Echocardiogram-measured left ventricular mass

Echocardiogram-measured left ventricular mass. Each subject had a midweek, post-dialysis echocardiogram performed at baseline, midway between the trial, and at the end of the study. The top half of the figure shows the four subjects (each a different color) who received the treatment sequence of 3 days per week hemodialysis followed by 5 days per week hemodialysis. The bottom half of the figure shows the remaining four subjects (each a different color) who received the treatment sequence of 5 days per week hemodialysis followed by 3 days per week hemodialysis.

Supplemental Table 1. Pre-specified blood pressure outcomes by treatment sequence

Subject / 3 days per week hemodialysis / Cross-over direction / 5 days per week hemodialysis
Total days with event
(1st day event sustained) / Total days assessed
(max 36) / Total days with event
(1st day event sustained) / Total days assessed
(max 36)
Event=10% reduction in pre-HD systolic blood pressure, relative to baseline
1 / 1 / 36 / 3x/week ►5x/week / 1 / 36
3 / 0 / 36 / 3x/week ►5x/week / 2 / 36
6 / 7 / 36 / 3x/week ►5x/week / 22 (DAY 8) / 34
8† / 0 / 24 / 3x/week ►5x/week / †withdrew/transplant
2 / 7 / 36 / 3x/week◄ 5x/week / 16 (DAY 25) / 36
4 / 0 / 36 / 3x/week◄ 5x/week / 4 / 36
7 / 0 / 36 / 3x/week◄ 5x/week / 5 / 36
5‡ / 2 / 6 / 3x/week◄ 5x/week / 0 / 36
Event=10% reduction in pre-HD diastolic blood pressure, relative to baseline
1 / 0 / 36 / 3x/week ►5x/week / 7 / 36
3 / 1 / 36 / 3x/week ►5x/week / 14 / 36
6 / 14 (DAY 16) / 36 / 3x/week ►5x/week / 24 (DAY 5) / 34
8† / 16 (DAY 22) / 24 / 3x/week ►5x/week / †withdrew/transplant
2 / 23 (DAY 2) / 36 / 3x/week◄ 5x/week / 21 (DAY 11) / 36
4 / 0 / 36 / 3x/week◄ 5x/week / 10 / 36
7 / 0 / 36 / 3x/week◄ 5x/week / 8 / 36
5‡ / 2 / 6 / 3x/week◄ 5x/week / 4 / 36
Event=days requiring fewer antihypertensive medications or lower dosages, relative to baseline
1 / 5 (DAY 32) / 36 / 3x/week ►5x/week / 0 / 36
3 / 0 / 36 / 3x/week ►5x/week / 33 (DAY 4) / 36
6 / 0 / 36 / 3x/week ►5x/week / 8 (DAY 29) / 36
8† / 10 (DAY 15) / 24† / 3x/week ►5x/week / †withdrew/transplant
2 / 0 / 36 / 3x/week◄ 5x/week / 0 / 36
4 / 0 / 36 / 3x/week◄ 5x/week / 30 (DAY 7) / 36
7 / 0 / 36 / 3x/week◄ 5x/week / 6 (DAY 31) / 36
5‡ / 0 / 6 / 3x/week◄ 5x/week / 22 (DAY 15) / 36

The table summarizes the number of favorable blood pressure events for each subject, across each study period, for the three separate outcomes (systolic, diastolic, and medications), as defined above. Shaded squares are treatment period 1 and non-shaded squares are treatment period 2. The bold denotes subjects with favorable events sustained for ≥3 consecutive treatments and the non-bold subjects with favorable events that were not sustained (3 versus 5 days per week p>0.3 by exact McNemar for all outcomes). Post-hoc, we used Poisson regression to analyze counts of these events, regardless if they were sustained or not (p<0.05 for the treatment effect of 3 versus 5 days per week on each outcome, favoring 5 days per week). In the regression models, treatment effects were p<0.05 for systolic and diastolic blood pressure and p=0.24 for antihypertenstive medications. Analyses excluded subject 8† who withdrew from the study due to kidney transplant during treatment period 1 and subject 5‡ who withdrew two weeks after starting the 3 days per week study period (treatment period 2).

Supplemental Table 2. Secondary outcomes

3 days per week hemodialysis / 5 days per week hemodialysis / p-value*
Baseline n=6 / Week 12 n=6 / %∆ baseline / Baseline n=6 / Week 12 n=6 / %∆ baseline
Anemia management
Erythropoietin dose
(units/week) / 8625
[4500, 12,000] / 3750
[1000, 6000] / -25.0%
[-66.7%, 0%] / 5250
[2000, 11,400] / 4500
[1000, 9000] / -25%
[-50,0%, 0%] / 0.38
Post-dialysis hemoglobin (g/dL) / 12.4
[11.6, 14.5]; N=5 / 12.2
[10.4, 14.1] / -2.4%
[-6.0%, 0.7%] / 13.6
[13.3, 14.4] / 12.4
[11.8, 13.3] / -5.9%
[-7.6%, -1.7%] / 0.60
Elemental iron dose (mg/month) / 125.0
[100.0, 125.0] / 125.0
[100.0, 140.0] / 0%
[-79.7%, 0%] / 125.0
[125.0, 140.0] / 125.0
[100.0, 125.0] / 0%
[0%, 0%] / 0.57
Serum iron
(mcg/dL ) / 55.7
[30.0, 69.0] / 57.0
[50.3, 83.0] / 29.9%
[-14.5%, 80.4%] / 52.0
[42.0, 62.0] / 39.0
[24.0, 56.4] / -23.9%
[-41.8%, 8.6%] / 0.12
Bone metabolism
Phosphorus (mg/dL) / 6.3
[4.4, 8.5] / 6.8
[5.4, 9.1] / 25.1%
[-5.7%, 40.0%] / 5.6
[4.8, 6.2] / 4.8
[3.6, 7.0] / 2.1%
[-38.6%, 31.4%] / 0.28
Calcium (mg/dL) / 9.0
[8.8, 9.3] / 9.0
[8.7, 9.6] / -0.9%
[-6.5%, 7.2%] / 9.1
[8.7, 9.5] / 9.1
[9.0, 9.5] / 4.4%
[-2.2%, 5.8%] / 0.36
Calcium/phosphorus product / 60.6
[38.7, 72.2] / 63.4
[48.1, 91.9] / 20.4%
[3.3%, 24.1%] / 51.0
[48.5, 58.9] / 45.1
[32.4, 70.0] / 7.7%
[-39.9%, 45.7%] / 0.30
Phosphate binders prescribed / 1.0
[1.0, 2.0] / 1.5
[1.0, 2.0] / 0%
[0%, 0%] / 1.5
[1.0, 2.0] / 1.5
[1.0, 2.0] / 0%
[0%, 0%] / -
Calcitriol dose
(mcg/week) / 2.9
[1.5, 3.5] / 2.6
[2.3, 3.5] / 0%
[0%, 50%] / 2.9
[2.3, 3.5] / 2.6
[1.8, 3.5] / -6.3%
[-50.0%, 0%] / 0.25
Intact parathyroid hormone (pg/mL) / 411
[266, 781] / 275
[264, 729]; N=5 / 38.9%
[-0.8%, 97.6%] / 264
[191, 372] / 307
[238, 403] / 5.3%
[-38.3%, 83.8%] / 0.30
Inflammatory markers
C-reactive protein (mg/dL) / 0.7
[0.5, 1.3] / 0.7
[0.4, 1.1] / 1.2%
[-15.4%, 63.3%] / 0.6
[0.5, 1.3] / 0.5
[0.4, 2.4] / 0%
[-10.5%, 0%] / 0.78
Beta 2-microglobulin (mg/L) / 37.0
[25.5, 43.2] / 20.8
[6.1, 25.8] / -38.3%
[-88.0%, -15.1%] / 30.7
[18.6, 33.4] / 30.7
[30.2, 37.9] / 0.3%
[-1.9%, 15.9%] / 0.16
Homocysteine (µmol/L) / 16.0
[12.1, 25.6] / 14.6
[11.2, 22.3] / -8.1%
[-11.0%, 1.1%] / 17.1
[11.7, 23.7] / 12.8
[11.8, 19.6] / -23.1%
[-27.4%, -7.2%] / 0.13

Data shown as median [interquartile range]. Darbopoietin (1 mcg) dosing converted to erythropoietin (200 units) and paricalcitol (3 mcg) converted to calcitriol (1 mcg). For the two subjects who stopped the trial prematurely, only data from the completed study period (full 12 weeks) is included in order to calculate the percentage change from baseline (%∆ baseline). *Mixed effects analysis of variance model with terms for treatment period and for subject included as a random effect. As shown, all p-value>0.10. P-value could not be calculated for number of phosphate binders prescribed because there was no change across treatments.

Supplemental Table 3. Additional laboratory values and dialysis prescription

3 days per week hemodialysis / 5 days per week hemodialysis / p-value*
Baseline n=6 / Week 12 n=6 / %∆ baseline / Baseline n=6 / Week 12 n=6 / %∆ baseline
Laboratory values
Serum sodium
(meq/L) / 139.5
[138.0, 142.0] / 141.0
[139.0, 142.0] / 0%
[-1.4%, 1.4%] / 140.0
[137.0, 141.0] / 142.0
[140.0, 142.0] / 1.1%
[0.7%, 2.1%] / 0.30
Serum potassium
(meq/L) / 4.6
[4.1, 4.8] / 4.0
[3.7, 4.5] / -8.7%
[-17.8%, -2.1%] / 4.1
[3.6, 4.9] / 4.5
[4.4, 4.8] / 4.8%
[-2.5%, 22.2%] / 0.14
Serum bicarbonate (meq/L) / 23.5
[21.0, 27.0] / 24.0
[22.0, 26.0] / -0.6%
[-11.1%, 14.3%] / 25.5
[24.0, 26.0] / 24.5
[24.0, 28.0] / 0.6%
[-4.0%, 7.7%] / 0.64
Pre-blood urea nitrogen (mg/dL) / 54.5
[39.0, 80.0] / 64.0
[49.0, 87.7] / -6.8%
[-12.1%, 61.4%] / 52.5
[39.0, 72.0] / 60.5
[40.0, 68.0] / 9.1%
[-5.6%, 64.1%] / 0.81
Post-blood urea nitrogen (mg/dL) / 12.0
[9.0, 15.0] / 10.0
[7.0, 16.0]; N=5 / -16.3%
[-30.0%, 14.3%] / 11.0
[8.0, 17.0] / 19.0
[15.0, 27.0] / 58.8%
[46.2%, 66.7%] / 0.16
Post-albumin
(g/dL) / 4.6
[3.8, 4.6] / 4.6
[4.0, 4.8] / 7.6%
[-12.7%, 15.8%] / 4.7
[4.2, 4.8] / 4.2
[4.0, 4.3] / -3.4%
[-6.6%, 0.2%] / 0.76
Ferritin
(ng/mL) / 551.7
[390.0, 728.2] / 562.0
[557.0, 702.8] / -6.8%
[-16.1%, 43.6%] / 495.5
[458.0, 860.0] / 642.4
[458.0, 1254.0] / -3.0%
[-9.3%, 8.5%] / 0.37
Transferrin
(mg/dL) / 133.0
[107.0, 147.0] / 136.5
[114.0, 166.0] / 2.7%
[-2.0%, 6.5%] / 122.0
[113.0, 169.1] / 122.5
[119.0, 165.0] / 9.1%
[-14.2%, 16.4%] / 0.70
Dialysis prescription
Dry weight
(kg) / 41.5
[35.0, 56.0] / 44.0
[35.0, 56.5] / 1.9%
[0%, 9.5%] / 43.5
[34.0, 56.5] / 44.0
[35.0, 57.0] / 1.6%
[1.0%, 2.9%] / 0.57
Blood flow
(ml/min) / 275.0
[200.0, 350.0] / 275.0
[200.0, 350.0] / 0%
[0%, 0%] / 275.0
[200.0, 350.0] / 250.0
[180.0, 350.0] / 0%
[0%, 0%] / 0.36
Dialysate flow (ml/min) / 600.0
[500.0, 700.0] / 600.0
[500.0, 700.0] / 0%
[0%, 0%] / 600.0
[500.0, 700.0] / 600.0
[500.0, 700.0] / 0%
[0%, 0%] / -
Potassium bath (meq/L) / 2.0
[1.0, 2.0]; N=5 / 2.0
[1.0, 2.0] / 0%
[0%, 0%] / 1.8
[1.0, 2.0] / 2.0
[1.5, 2.0] / 0%
[0%, 50%] / 0.23
Bicarbonate bath (meq/L) / 40.0
[40.0, 40.0]; N=5 / 40.0
[35.0, 40.0] / 0%
[0%, 0%] / 40.0
[35.0, 40.0] / 40.0
[35.0, 40.0] / 0%
[0%, 0%] / -
Calcium bath (meq/L) / 2.5
[2.5, 2.5]; N=5 / 2.5
[2.5, 3.5] / 0%
[0%, 0%] / 2.5
[2.5, 3.5] / 2.8
[2.5, 3.5] / 0%
[0%, 0%] / 0.32
Dialysate temperature (C) / 37
[37, 37] / 37
[37, 37] / 0%
[0%, 0%] / 37
[37, 37] / 37
[37, 37] / 0%
[0%, 0%] / 0.31

*Mixed effects analysis of variance model with terms for treatment period and subject included as a random effect. As shown, all p-value>0.10. P-value could not be calculated for dialysate flow and bicarbonate bath because there was no change across treatments.