Comparison of citrate dialysate in pre- and post-dilution online hemodiafiltration: effect on clot formation and adequacy of dialysis in hemodialysis patients

Figures & data

Figure 1. Study flow chart.

Table 1. Restitutional clotting scale.

Clotting score	External appearance of venous chamber
0	No or very little residual blood in the filters
1	Residual blood in less than 10% of the fibers
2	Residual blood 10–25%
3	Residual blood 25–50%
4	Residual blood > 50%

Adapted from: [17].

Table 2. Baseline characteristics.

Characteristics (n = 8)
	n	%
age (yrs.), Mean ± SD (Min - Max)	68.38 ± 17.00 (38–86)
sex
F	5	62.50
M	3	37.50
BMI (kg/m^2), Mean ± SD (Min - Max)	23.43 ± 5.54 (18.29–31.56)
DM	3	37.5
HT	8	100.00
CAD	3	37.50
vascular access
AVF	6	75.00
permanent catheter	2	25.00
cause of ESRD
CGN	4	50.00
DKD	3	37.50
IgA	1	12.50
gout	2	25.00
dialysis vintage (yr), Median (IQR)	8.05 (3.12–14.7)

SD: standard deviation; BMI: body mass index; CGN: chronic glomerulonephritis; DKD: diabetic kidney disease; DM: diabetes mellitus; HT: hypertension; CAD: cardiovascular disease; AVF.

Table 3. Treatment characteristics.

Qb convection
Outcome	Pre phase	Phase 1 heparin 50%		Phase 2 heparin 25%		Phase 3 heparin-free
	Mean ± SD/Absolute difference	p Value	Mean ± SD/Absolute difference	p Value	Mean ± SD/Absolute difference	p Value	Mean ± SD/Absolute difference	p Value
blood flow
Predilution	291.93 ± 9.86		295.31 ± 6.71		297.25 ± 3.91		298.37 ± 3.65	0.079^c
Postdilution	296.09 ± 5.75		301.44 ± 9.91		294.43 ± 20.45		301.47 ± 11.64	0.307^c
Change from pre to post (95% CI)^a	4.17 (-3.08 to 11.41)	0.260	6.13 (-1.12 to 13.37)	0.097	−2.82 (-10.07 to 4.42)	0.445	3.1 (-4.14 to 10.34)	0.402
Difference from heparin-free (95% CI)^b	1.07 (-8.51 to 10.65)	0.827	3.03 (-6.55 to 12.61)	0.535	−5.92 (-15.5 to 3.65)	0.225	Ref.
Substitute volume
Predilution	41.97 ± 4.20		40.93 ± 4.06		43.71 ± 6.09		43.79 ± 6.27	0.181^c
Postdilution	45.61 ± 5.57		18.37 ± 2.41		17.59 ± 2.87		18.85 ± 2.16	<0.001^c
Change from pre to post (95% CI)^a	3.64 (0.47, 6.80)	0.024	−22.56 (-25.73 to −19.39)	< 0.001	−26.12 (-29.28 to −22.95)	< 0.001	−24.93 (-28.1 to −21.77)	<0.001
Difference from heparin-free (95% CI)^b	28.57 (24.82 to 32.32)	< 0.001	2.37 (-1.38 to 6.12)	0.215	−1.18 (-4.93 to 2.57)	0.536	Ref.
Substitute rate
Predilution	174.89 ± 17.51		170.55 ± 16.92		182.11 ± 25.38		182.44 ± 26.13	0.181^c
Postdilution	190.04 ± 23.20		76.55 ± 10.06		73.28 ± 11.98		78.55 ± 8.98	< 0.001^c
Change from pre to post (95% CI)^a	15.15 (1.96 to 28.35)	0.024	−94.01 (-107.20 to −80.81)	< 0.001	−108.83 (-122.02 to −95.63)	< 0.001	−103.89 (-117.09 to −90.70)	<0.001
Difference from heparin-free (95% CI)^b	119.05 (103.42 to 134.68)	< 0.001	9.89 (-5.74 to 25.52)	0.215	−4.93 (-20.56 to 10.7)	0.536	Ref.
Ultrafiltration
Predilution	2.64 ± 0.98		2.65 ± 0.91		2.46 ± 0.80		2.56 ± 1.08	0.709^c
Postdilution	2.15 ± 0.84		2.35 ± 1.02		2.29 ± 1.07		2.35 ± 0.94	0.701^c
Change from pre to post (95% CI)^a	−0.49 (−0.91 to −0.06)	0.024	−0.30 (−0.73 to 0.12)	0.163	−0.17 (−0.59 to 0.25)	0.431	−0.20 (−0.63 to 0.22)	0.350
Difference from heparin-free (95% CI)^b	−0.29 (−0.77 to 0.20)	0.251	−0.10 (−0.59 to 0.39)	0.689	0.03 (−0.46 to 0.52)	0.898	Ref.
Effective convective volume
Predilution	22.33 ± 1.08		22.65 ± 0.96		23.29 ± 1.57		23.23 ± 1.46	0.087^c
Postdilution	23.41 ± 1.59		20.72 ± 1.58		19.87 ± 2.45		21.21 ± 1.75	< 0.001^c
Change from predilution (95% CI)^a	1.08 (−0.04 to 2.20)	0.059	−1.93 (-3.05 to −0.81)	0.001	−3.41 (-4.54 to −2.29)	< 0.001	−2.02 (-3.15 to −0.90)	< 0.001
Difference from heparin-free (95% CI)^b	3.11 (1.63 to 4.58)	<0.001	0.10 (-1.38 to 1.57)	0.899	−1.39 (-2.87 to 0.09)	0.065	Ref.
Hct
Predilution	35.23 ± 4.47		32.54 ± 3.95		32.39 ± 4.44		33.28 ± 4.01	0.119^c
Postdilution	33.33 ± 4.30		34.26 ± 3.20		32.26 ± 2.74		32.76 ± 3.37	0.603^c
Change from pre to post (95% CI)^a	−1.90 (-4.68 to 0.88)	0.181	1.73 (-1.06 to 4.51)	0.225	−0.13 (-2.91 to 2.66)	0.930	−0.51 (-3.30 to 2.27)	0.718
Difference from heparin-free (95% CI)^b	−1.39 (-4.96 to 2.19)	0.447	2.24 (-1.34 to 5.81)	0.220	0.39 (-3.19 to 3.96)	0.832	Ref.
DF
Predilution	50.18 ± 2.35		52.13 ± 2.85		50.8 ± 3.75		50.55 ± 4.27	0.238^c
Postdilution	49.24 ± 2.94		–		–		–	–
Change from predilution (95% CI)^a	−0.94 (-2.91 to 1.04)	0.352	–	–	–	–	–	–
Difference from heparin-free (95% CI)^b	–	–	–	–	–	–	Ref.
Qfeff
Predilution	87.46 ± 5.50		88.54 ± 5.13		91.77 ± 6.81		91.31 ± 6.48	0.051^c
Postdilution	93.07 ± 6.62		76.55 ± 10.06		73.28 ± 11.98		78.55 ± 8.98	< 0.001^c
Change from predilution (95% CI)^a	5.62 (0.43 to 10.80)	0.034	−11.99 (-17.18 to −6.80)	< 0.001	−18.49 (-23.68 to −13.30)	< 0.001	−12.76 (-17.95 to −7.57)	< 0.001
Difference from heparin-free (95% CI)^b	18.38 (11.43 to 25.33)	< 0.001	0.77 (-6.18 to 7.72)	0.827	−5.72 (-12.68 to 1.23)	0.106	Ref.

^a Absolute difference is the mean change from pre-dilution with 95% CIs in the same phase estimated by a linear mixed-effects model adjusted for baseline.

^b Absolute difference is the mean difference of each parameter from difference in heparin free with 95% Cis in the same phase estimated by a linear mixed-effects model adjusted for baseline.

^c Different time point estimated by One Way repeated measures ANOVA.

Significant if p < 0.05.

DF: Dilution factor; Qfeff: effective convection flow rate = substitute volume*1000/t*DF.

Table 4. Clotting scores in various phases in pre and postdilution oL-HDF.

Visual clotting score	Predilution	Postdilution	Difference (95% CI)^a	p value
pre/washout	1.65 ± 0.27	2.19 ± 0.46	0.54 (0.27, 0.81)	<0.001*
Phase 1 (heparin 50%)	1.88 ± 0.41	2.32 ± 0.17	0.45 (0.18, 0.72)	0.001*
Phase 2 (heparin 25%)	2.10 ± 0.23	2.42 ± 0.23	0.31 (0.04, 0.58)	0.023
Phase 3 (no heparin)	2.48 ± 0.27	2.51 ± 0.18	0.03 (−0.24, 0.30)	0.815

Absolute difference is the mean change from pre -dilution in the same phase with 95% CIs estimated by a linear mixed-effects model adjusted for baseline.

Table 5. Biochemical parameters, ESA doses, iron supplement per week, and reuse number of dialyzers after changing from acetate to citrate dialysate and reduce heparin in stepwise fashion.

Labs
Outcome	Pre phase		Phase 1 heparin 50%		Phase 2 heparin 25%		Phase 3 heparin-free
	Mean ± SD/Absolute difference	p Value	Mean ± SD/Absolute difference	p Value	Mean ± SD/Absolute difference	p Value	Mean ± SD/Absolute difference	p Value
Hemoglobin
Pre-dilution	11.20 ± 1.21		10.38 ± 1.05		10.29 ± 1.16		10.74 ± 1.08	0.168^c
Post-dilution	10.68 ± 1.26		10.86 ± 0.82		10.26 ± 0.95		10.49 ± 0.92	0.659^c
Change from pre-dilution (95% CI)^a	−0.53 (-1.41 to 0.36)	0.247	0.49 (−0.40 to 1.38)	0.282	−0.03 (−0.91 to 0.86)	0.956	−0.25 (-1.14 to 0.64)	0.581
Difference from heparin-free (95% CI)^b	−0.28 (-1.43 to 0.88)	0.642	0.74 (−0.42 to 1.90)	0.212	0.23 (−0.93 to 1.38)	0.704	Ref.
ESA Dose (%)
Predilution	100.00 ± 0		100.00 ± 46.29		104.75 ± 42.20		104.13 ± 29.16	0.842^c
Postdilution	96.88 ± 20.86		106.25 ± 17.68		106.88 ± 18.34		125.00 ± 38.87	0.189^c
Change from pre-dilution (95% CI)^a	−3.13 (-30.3 to 24.05)	0.822	6.25 (-20.92 to 33.42)	0.652	2.125 (-25.05 to 29.3)	0.878	20.88 (-6.3 to 48.05)	0.132
Difference from heparin-free (95% CI)^b	−24 (-53.92 to 5.92)	0.116	−14.63 (-44.54 to 15.29)	0.338	−18.75 (-48.67 to 11.17)	0.219	Ref.
Ferritin
Predilution	506.34 ± 446.70		601.48 ± 491.20		803.25 ± 461.82		611.88 ± 275.42	0.090^c
Postdilution	513.75 ± 326.29		916.50 ± 748.54		545.91 ± 317.19		449.50 ± 291.82	0.110^c
Change from pre-dilution (95% CI)^a	7.41 (-294.75 to 309.57)	0.962	315.03 (12.87 to 617.18)	0.041	−257.34 (-559.5 to 44.82)	0.095	−162.38 (-464.53 to 139.78)	0.292
Difference from heparin-free (95% CI)^b	169.79 (-200.98, 540.55)	0.369	477.40 (106.64 to 848.16)	0.012	−94.96 (-465.73 to 275.80)	0.616	Ref.
Iron supplement per wk
Predilution	25.00 ± 26.73		28.13 ± 36.44		75.00 ± 90.63		28.13 ± 41.05	0.216^c
Postdliution	31.25 ± 70.39		43.75 ± 87.37		12.5 ± 26.73		21.88 ± 24.78	0.636^c
Change from pre-dilution (95% CI)^a	6.25 (-43.91 to 56.41)	0.807	15.63 (-34.53 to 65.78)	0.541	−62.50 (-112.66 to −12.34)	0.015	−6.25 (-56.41 to 43.91)	0.807
Difference from heparin-free (95% CI)^b	12.5 (-58.43 to 83.43)	0.730	21.88 (-49.06 to 92.81)	0.546	−56.25 (-127.18 to 14.68)	0.120	Ref.
Tsat
Predilution	0.32 ± 0.10		0.24 ± 0.07		0.31 ± 0.09		0.33 ± 0.11	0.088^c
Postdilution	0.30 ± 0.10		0.34 ± 0.08		0.30 ± 0.10		0.26 ± 0.07	0.276^c
Change from pre-dilution (95% CI)^a	−0.02 (−0.09 to 0.05)	0.618	0.10 (0.03 to 0.17)	0.004	−0.01 (−0.08 to 0.05)	0.667	−0.07 (−0.14 to 0)	0.053
Difference from heparin-free (95% CI)^b	0.05 (−0.04 to 0.14)	0.297	0.17 (0.07 to 0.26)	< 0.001	0.05 (−0.04 to 0.15)	0.274	Ref.
Kt/V
Predilution	2.36 ± 0.52		1.74 ± 0.49		1.98 ± 0.28		1.91 ± 0.37	0.006^c
Postdilution	1.87 ± 0.33		1.91 ± 0.38		2.00 ± 0.62		1.83 ± 0.36	0.610^c
Change from pre-dilution (95% CI)^a	−0.50 (−0.81 to −0.19)	0.002	0.17 (−0.14 to 0.48)	0.286	0.02 (−0.29 to 0.33)	0.900	−0.08 (−0.39 to 0.23)	0.627
Difference from heparin-free (95% CI)^b	−0.42 (−0.83 to −0.01)	0.046	0.25 (−0.17 to 0.66)	0.241	0.10 (−0.32 to 0.51)	0.644	Ref.
Ca
Predilution	9.23 ± 0.88		8.85 ± 0.72		8.56 ± 0.66		8.54 ± 0.75	0.022^c
Postdilution	8.79 ± 0.76		8.41 ± 1.17		8.25 ± 0.83		8.50 ± 0.76	0.230^c
Change from pre-dilution (95% CI)^a	−0.44 (−0.94 to 0.06)	0.086	−0.44 (−0.94 to 0.06)	0.086	−0.31 (−0.81 to 0.19)	0.220	−0.04 (−0.54 to 0.46)	0.883
Difference from heparin-free (95% CI)^b	−0.40 (-1.04 to 0.24)	0.220	−0.40 (-1.04 to 0.24)	0.220	−0.28 (−0.91 to 0.36)	0.399	Ref.
iCa
Predilution	4.65 ± 0.34		4.46 ± 0.19		4.45 ± 0.30		4.59 ± 0.29	0.180^c
Postdilution	4.56 ± 0.29		4.56 ± 0.37		4.51 ± 0.46		4.67 ± 0.21	0.331^c
Change from pre-diution (95% CI)^a	−0.08 (−0.30 to 0.13)	0.451	0.09 (−0.12 to 0.31)	0.391	0.06 (−0.15 to 0.27)	0.583	0.08 (−0.14 to 0.29)	0.472
Difference from heparin-free (95% CI)^b	−0.16 (−0.41 to 0.09)	0.206	0.02 (−0.23 to 0.26)	0.906	−0.02 (−0.27 to 0.23)	0.883	Ref.
iPTH
Predilution	406.49 ± 307.70		553.55 ± 435.21		524.84 ± 351.41		494.74 ± 292.65	0.665^c
Postdilution	421.29 ± 267.77		377.78 ± 199.09		345.81 ± 267.12		304.90 ± 195.91	0.517^c
Change from pre-dilution (95% CI)^a	14.80 (-192.23 to 221.83)	0.889	−175.78 (-382.80 to 31.25)	0.096	−179.03 (-386.05 to 28.00)	0.090	−189.84 (-396.87 to 17.19)	0.072
Difference from heparin-free (95% CI)^b	204.64 (-62.58 to 471.85)	0.133	14.06 (-253.15 to 281.28)	0.918	10.81 (-256.40 to 278.03)	0.937	Ref.
hs-CRP
Predilution	4.19 ± 4.53		7.24 ± 10.54		6.30 ± 9.43		6.04 ± 5.42	0.810^c
Postdilution	4.87 ± 5.05		4.76 ± 3.47		9.70 ± 12.86		5.21 ± 3.89	0.342^c
Change from pre -dilution (95% CI)^a	0.68 (-5.09 to 6.45)	0.817	−2.90 (-8.86 to 3.07)	0.341	2.99 (-2.98 to 8.96)	0.326	−1.25 (-7.22 to 4.72)	0.681
Difference from heparin-free (95% CI)^b	1.93 (-5.80 to 9.66)	0.624	−1.65 (-9.49 to 6.20)	0.681	4.24 (-3.60 to 12.09)	0.289	Ref.
IL-6
Predilution	6.22 ± 3.68		7.03 ± 5.23		7.49 ± 4.55		5.94 ± 3.99	0.316^c
Postdilution	6.45 ± 4.07		6.99 ± 3.19		6.73 ± 3.79		7.32 ± 3.70	0.869^c
Change from pre -dilution (95% CI)^a	0.23 (-2.02 to 2.48)	0.840	−0.45 (-2.86 to 1.96)	0.716	−0.88 (-3.32 to 1.56)	0.478	1.13 (-1.20 to 3.47)	0.342
Difference from heparin-free (95% CI)^b	−0.90 (-3.93 to 2.13)	0.559	−1.58 (-4.70 to 1.54)	0.321	−2.02 (-5.16 to 1.13)	0.209	Ref.
max use
Predilution	6.00 ± 0		9.38 ± 2.88		6.50 ± 3.63		7.75 ± 2.92	0.050^c
Postdilution	5.25 ± 1.04		8.00 ± 2.27		7.25 ± 2.82		5.63 ± 1.92	0.014^c
Change from pre-dilution (95% CI)^a	−0.75 (-2.77 to 1.27)	0.466	−1.38 (-3.39 to 0.64)	0.182	0.75 (-1.27 to 2.77)	0.466	−2.13 (-4.14 to −0.11)	0.039
Difference from heparin-free (95% CI)^b	1.38 (-1.31 to 4.06)	0.315	0.75 (-1.93 to 3.43)	0.584	2.88 (0.19 to 5.56)	0.036

^a Absolute difference is the mean change from pre -dilution in the same phase with 95% CIs estimated by a linear mixed-effects model adjusted for baseline.

^b Absolute difference is the mean difference of each parameter from difference in heparin-free with 95% Cis in the same phase estimated by a linear mixed-effects model adjusted for baseline.

^c Different time point estimated by One-Way repeated measures ANOVA.

Significant if p < 0.05.

Max use: Number of reuses in each phase.

iCa: ionized calcium.

Figure 2. Comparison between erythrocyte stimulating agents dose between pre-and post- dilution online hemodiafiltration.

Figure 3. Mental component summary (MCS) and physical component summary (PCS) are comparable between pre and post-dilution mode A: Physical component B: Mental component Comparison between erythrocyte stimulating agents between pre- and post- dilution online hemodiafiltration

Table 6. KDQOL-SF-12 physical /mental composite score.

Outcome	Pre phase		Phase 1 heparin 50%		Phase 2 heparin 25%		Phase 3 heparin-free
	Mean ± SD/Absolute difference	p Value	Mean ± SD/Absolute difference	p Value	Mean ± SD/Absolute difference	p Value	Mean ± SD/Absolute difference	p Value
SF-12 Physical Composite
Predilution	32.96 ± 7.21		34.67 ± 9.56		36.14 ± 6.66		38.21 ± 12.52
Postdilution	40.56 ± 10.17		43.64 ± 11.77		38.96 ± 11.25		39.25 ± 9.51
Change from predilution (95% CI)^a	7.6 (1.57, 13.63)	0.014	8.97 (2.94, 15.00)	0.004	2.82 (-3.21, 8.85)	0.359	1.03 (-4.99, 7.06)	0.737
Difference from heparin-free (95% CI)^b	6.56 (-1.24, 14.36)	0.099	7.94 (0.13, 15.74)	0.046	1.79 (-6.01, 9.59)	0.653	Ref.
SF-12 Mental Composite
Predilution	46.47 ± 6.79		47.14 ± 5.86		44.52 ± 6.46		51.73 ± 8.92
Postdilution	48.70 ± 9.08		45.48 ± 7.74		45.24 ± 5.83		41.21 ± 5.55
Change from pre prodilution (95% CI)^a	2.23 (-2.79, 7.26)	0.383	−1.66 (-6.68, 3.36)	0.517	0.72 (-4.3, 5.74)	0.780	−10.52 (-15.54, −5.5)	<0.001
Difference from heparin-free (95% CI)^b	12.75 (6.45, 19.06)	<0.001	8.86 (2.55, 15.17)	0.006	11.24 (4.93, 17.54)	<0.001	Ref.

^a Absolute difference is the mean change from predilution with 95%CIs estimated by a linear mixed-effects model adjusted for baseline.

^b Absolute difference is the mean difference from heparin-free with 95%CIs estimated by a linear mixed-effects model adjusted for baseline.

Significant if p < 0.05.

Aniort J, Petitclerc T, Créput C. Safe use of citric acid-based dialysate and heparin removal in postdilution online hemodiafiltration. Blood Purif. 2012;34(3-4):336–343. doi:10.1159/000345342.

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Data availability statement

Data supporting the findings of this study are available from the corresponding author. Data supporting the findings of this study are openly available in ‘figshare’ at http://10.6084/m9.figshare.21971570.