Relationship between effective blood flow rate and clinical outcomes in maintenance hemodialysis patients: a single-center study

Figures & data

Figure 1. Flow diagram showing the patient enrollment and follow-up.

Figure 2. The distribution of time-averaged eBFR in enrolled patients.

Table 1. Demographics and patient characteristics in two groups based on the time-averaged eBFR.

	Overall	eBFR ≤ 275 mL/min	eBFR > 275 mL/min	P
N (%)	175	87 (49.7%)	88 (50.3%)	–
Follow-up (months)	32.8 (21.7, 44.1)	29.2 (16.1, 39)	36.6 (24.7, 48.1)	0.001
Age (years)	59.1 ± 13.9	62.8 ± 13.8	55.4 ± 13.1	<0.001
Female	34.9%	43.7%	26.1%	0.015
Vintage (years)	4.3 (3.1, 6.8)	4 (2.8, 6.4)	4.4 (3.3, 7)	0.358
Diabetes	37.7%	64.40%	60.20%	0.641
Hypertension	86.3%	80.5%	92%	0.029
History of CVD	18.3%	25.3%	11.4%	0.020
HDF ≥ 1/week	65.1%	57.5%	72.7%	0.034
Primary kidney diseases
Glomerulonephritis	33.7%	31%	36.4%	0.523
Diabetic nephropathy	30.9%	28.7%	33.0%	0.624
Hypertensive nephropathy	15.4%	16.1%	14.8%	0.837
Others	20.0%	24.1%	15.9%	0.190
Medication
Antiplatelet	59.4%	57.5%	61.4%	0.646
Antihypertensive	88%	85.1%	90.9%	0.254
Phosphate binders	94.3%	90.8%	97.7%	0.057

CVD: cardiovascular disease; HDF: hemodiafiltration.

Table 2. The baseline and time-averaged values in two groups based on the time-averaged eBFR.

	Baseline values				Time-averaged values
	Overall	eBFR ≤ 275 mL/min	eBFR > 275 mL/min	P	Overall	eBFR ≤ 275 mL/min	eBFR > 275 mL/min	P
N (%)	175	87 (49.7%)	88 (50.3%)	-	175	87 (49.7%)	88 (50.3%)	-
Dialysis data
eBFR (ml/min)	274 ± 23	257 ± 17	289 ± 17	<0.001	276 ± 24	257 ± 18	293 ± 13	<0.001
pBFR (ml/min)	282 ± 25	273 ± 24	290 ± 22	<0.001	295 ± 25	278 ± 21	309 ± 19	<0.001
spKt/V	1.46 ± 0.30	1.49 ± 0.32	1.42 ± 0.26	0.118	1.55 ± 0.24	1.55 ± 0.21	1.55 ± 0.26	0.700
IDWG (kg)	2.35 ± 0.75	2.19 ± 0.74	2.49 ± 0.73	0.008	2.50 ± 0.77	2.24 ± 0.71	2.76 ± 0.75	<0.001
SBP (mmHg)	137.4 ± 15.5	138.6 ± 16.4	136.2 ± 14.5	0.251	140.7 ± 14.4	141.1 ± 15.1	140 ± 14.9	0.642
DBP (mmHg)	77.3 ± 10.5	77.2 ± 11.7	77.4 ± 9.2	0.871	77.9 ± 10.5	77.2 ± 11.2	78.4 ± 10.2	0.461
Laboratory tests
CRE (µmol/L)	792 (622, 976)	677 (527, 919)	883 (666, 1065)	<0.001	860.8 (701, 1040)	781 (651, 905)	960 (813, 1143)	<0.001
ALB (g/L)	37.5 ± 4.5	36.3 ± 5.1	38.6 ± 3.5	0.003	38.8 ± 2.9	37.9 ± 3.3	39.6 ± 1.9	<0.001
CRP (mg/L)	3.5 (1.3, 8.9)	4.17 (1.8, 11.1)	2.5 (1, 7.3)	0.021	4.7 (2.1, 9.6)	5.8 (2.6, 11.9)	3.7 (1.8, 7.8)	0.016
CA (mmol/L)	2.16 ± 0.21	2.17 ± 0.21	2.15 ± 0.2	0.503	2.15 ± 0.15	2.16 ± 0.15	2.15 ± 0.15	0.726
P (mmol/L)	1.74 ± 0.61	1.66 ± 0.63	1.82 ± 0.59	0.102	1.75 ± 0.37	1.71 ± 0.37	1.8 ± 0.37	0.122
PTH (ng/ml)	249 (150, 369)	236 (130, 346)	256 (161, 377)	0.271	278 (198, 383)	272 (189, 357)	297 (215, 405)	0.096
Na (mmol/L)	137.1 ± 2.8	137.1 ± 3.2	137.1 ± 2.2	0.724	137.1 ± 2.3	136.8 ± 2.4	137.2 ± 2.2	0.313
Mg (mmol/L)	1.04 ± 0.17	1.03 ± 0.17	1.05 ± 0.17	0.332	1.11 ± 0.12	1.09 ± 0.13	1.11 ± 0.12	0.239
K (mmol/L)	4.8 ± 0.8	4.8 ± 0.9	4.8 ± 0.7	0.791	4.7 ± 0.5	4.7 ± 0.5	4.7 ± 0.4	0.807
CO2 (mmol/L)	23.2 ± 3.7	23.6 ± 4.3	22.8 ± 2.8	0.137	23.3 ± 1.7	23.4 ± 1.9	23.3 ± 1.5	0.586
GLU (mmol/L)	7.5 (5.9, 10.2)	7.3 (5.8, 11)	7.7 (5.9, 9.9)	0.936	7.6 (6.4, 11.4)	7.8 (6.6, 11.4)	7.5 (6.3, 11.9)	0.337
TG (mmol/L)	1.72 (1.17, 2.53)	1.64 (1.08, 2.43)	1.75 (1.19, 2.82)	0.171	1.99 (1.48, 2.8)	1.84 (1.34, 2.64)	2.18 (1.55, 2.98)	0.046
β2-MG (mg/L)	24.0 (20.2, 33.9)	24.3 (19.4, 33.9)	23.9 (21.2, 33.5)	0.995	31.4 (26.1, 35.1)	31.9 (25.5, 36.7)	30.9 (26.2, 34.4)	0.456
β2-MG RR	0.62 (0.44, 0.73)	0.62 (0.46, 0.74)	0.62 (0.43, 0.72)	0.413	0.69 (0.62, 0.75)	0.65 (0.535, 0.75)	0.71 (0.66, 0.77)	<0.001
HB (g/L)	99.5 ± 19.8	97.1 ± 19.7	101.9 ± 19.8	0.118	111.3 ± 10.5	108.3 ± 12.4	114.2 ± 7.1	<0.001
BMI (kg/m^2)	24.3 ± 4.5	23.2 ± 3.4	25.2 ± 5.2	0.007	12.9 ± 2.7	12.1 ± 2.6	13.6 ± 2.6	<0.001
LTI (kg/m^2)	13.0 ± 2.8	12.4 ± 2.8	13.5 ± 2.7	0.016	24.4 ± 4.4	23.3 ± 3.1	25.5 ± 5.1	0.003
LVEF(%)	61.2 ± 8.9	60.8 ± 9.1	61.5 ± 8.8	0.637	62.0 ± 6.9	61.7 ± 7	62.1 ± 6.7	0.512

eBFR: effective blood flow rate; pBFR: prescribed blood flow rate; IDWG: interdialytic weight gain; SBP: systolic blood pressure; DBP: diastolic blood pressure; CRE: creatinine; ALB: albumin; CRP: C-reactive protein; CA: calcium; P: phosphate; PTH: parathyroid hormone; Na: sodium; Mg: magnesium; K: potassium; CO₂: carbon dioxide; GLU: glucose; TG: triglyceride; β₂-MG: β₂-microglobulin; β₂-MG RR: β₂-microglobulin reduction ratio; HB: hemoglobin; LTI: lean tissue index; BMI: body Mass Index; LVEF: left ventricular ejection fraction.

Figure 3. A. Unadjusted Kaplan–Meier curves for all-cause mortality in two groups based on time-averaged eBFR. B. Unadjusted Kaplan–Meier curves for new MACE in two groups based on time-averaged eBFR.

Table 3. The relationship between eBFR and clinical outcomes.

All-cause mortality
	Unadjusted			Adjusted
	Model 1			Model 2			Model 3
	HR	95% CI	P	HR	95% CI	P	HR	95% CI	P
eBFR
Categorical model:
≤275ml/min	16.15	3.79–68.7	<0.001	12.78	2.87–56.94	0.001	14.18	3.14–64.1	0.001
>275ml/min	1.00 (Reference)			1.00 (Reference)			1.00 (Reference)
Continuous model: per 20 ml/min higher eBFR	0.51	0.39–0.67	<0.001	0.36	0.23–0.56	<0.001	0.37	0.23–0.59	<0.001
All-cause mortality (propensity score-adjusted by age and CVD)
	Unadjusted			Adjusted
	Model 1			Model 2			Model 3
	HR	95% CI	P	HR	95% CI	P	HR	95% CI	P
eBFR
Categorical model:
≤275ml/min	12.60	2.89–54.85	0.001	11.85	2.68–52.27	0.001	11.06	2.46–49.73	0.002
>275ml/min	1.00 (Reference)			1.00 (Reference)			1.00 (Reference)
Continuous model: per 20 ml/min higher eBFR	0.50	0.35–0.71	<0.001	0.34	0.20–0.58	<0.001	0.32	0.18–0.59	<0.001
MACE
	Unadjusted			Adjusted
	Model 1			Model 2			Model 3
	HR	95% CI	P	HR	95% CI	P	HR	95% CI	P
eBFR
Categorical model:
≤275ml/min	4.16	2.26–7.67	<0.001	3.59	1.82–7.04	<0.001	3.76	1.91–7.40	<0.001
>275ml/min	1.00 (Reference)		1.00 (Reference)		1.00 (Reference)
Continuous model: per 20 ml/min higher eBFR	0.71	0.59–0.86	0.001	0.62	0.46–0.83	0.001	0.62	0.46–0.84	0.002
MACE (propensity score-adjusted by age and CVD)
		Unadjusted		Adjusted
	Model 1			Model 2			Model 3
	HR	95% CI	P	HR	95% CI	P	HR	95% CI	P
eBFR
Categorical model:
≤275ml/min	3.33	1.76–6.31	<0.001	3.15	1.62–6.11	0.001	3.17	1.63–6.17	0.001
>275ml/min	1.00 (Reference)			1.00 (Reference)			1.00 (Reference)
Continuous model: per 20 ml/min higher eBFR	0.69	0.53–0.89	0.005	0.56	0.39–0.79	0.001	0.56	0.39–0.80	0.001

Model 1 unadjusted.

Model 2 adjusted for age, sex, vintage, diabetes, and CVD.

Model 3 adjusted for Model 2 variables plus HDF and spKt/V.

Table 4. The baseline characteristics and data in the two groups based on the time-averaged eBFR after propensity score matching.

	Overall	eBFR ≤ 275 mL/min	eBFR > 275 mL/min	P
N (%)	122	60 (49.2%)	62 (50.8%)	–
Age (years)	59 ± 12.3	58.6 ± 12.3	59.3 ± 12.4	0.776
Male	72.1%	68.3%	75.8%	0.421
Vintage (years)	4 (2.6, 6.1)	3.9 (2.4, 6.9)	4.1 (3.1, 5.9)	0.795
Diabetes	43.40%	38.30%	48.40%	0.279
CVD	18.0%	21.7%	14.5%	0.352
eBFR (ml/min)	275 ± 19	261 ± 15	287 ± 14	<0.001
pBFR (ml/min)	281 ± 24	275 ± 23	287 ± 24	0.004
spKt/V	1.45 ± 0.29	1.48 ± 0.33	1.42 ± 0.26	0.281
IDWG (kg)	2.3 ± 0.7	2.3 ± 0.8	2.5 ± 0.7	0.178
SBP (mmHg)	138.8 ± 15	138.3 ± 17.1	139.2 ± 12.9	0.763
DBP (mmHg)	78 ± 10.2	79.2 ± 11.7	76.8 ± 8.4	0.214
Laboratory tests
CRE (µmol/L)	775 (624, 963)	718 (607, 938)	801 (640, 1039)	0.23
ALB (g/L)	37.4 ± 4.2	36.8 ± 5.1	37.8 ± 3.3	0.21
CRP (mg/L)	3.2 (1.4, 9.8)	3.7 (1.8, 10.9)	2.6 (1.1, 9.2)	0.15
CA (mmol/L)	2.16 ± 0.21	2.18 ± 0.22	2.14 ± 0.19	0.291
P (mmol/L)	1.72 ± 0.63	1.65 ± 0.66	1.79 ± 0.59	0.222
PTH (ng/ml)	257 (151, 372)	291 (151, 411)	242 (154, 331)	0.487
Na (mmol/L)	137.1 ± 2.7	137.4 ± 3.1	136.8 ± 2.3	0.253
Mg (mmol/L)	1.05 ± 0.17	1.04 ± 0.16	1.07 ± 0.17	0.296
K (mmol/L)	4.8 ± 0.8	4.9 ± 0.8	4.8 ± 0.8	0.702
CO2 (mmol/L)	23.2 ± 3.8	23.6 ± 4.6	22.9 ± 2.7	0.297
GLU (mmol/L)	7.8 (5.9, 10.8)	7.3 (5.6, 10.5)	8.4 (6.7, 10.9)	0.118
TG (mmol/L)	1.63 (1.12, 2.48)	1.65 (1.13, 2.45)	1.57 (1.12, 2.55)	0.952
β2-MG (mg/L)	23.8 (19.3, 33.9)	24.7 (19.4, 36.5)	22.8 (18.7, 29.3)	0.173
β2-MG RR	0.61 (0.41, 0.73)	0.64 (0.39, 0.75)	0.6 (0.41, 0.69)	0.116
HB (g/L)	99.1 ± 18.5	97.4 ± 19.1	100.6 ± 18.1	0.342
BMI (kg/m^2)	24.2 ± 4.5	23.3 ± 3.4	24.9 ± 5.2	0.053
LTI (kg/m^2)	13.3 ± 2.7	13 ± 2.8	13.5 ± 2.5	0.286
LVEF(%)	60.7 ± 8.5	59.5 ± 9.8	61.8 ± 6.8	0.136

CVD: cardiovascular disease; eBFR: effective BFR; pBFR: prescribed BFR; IDWG: interdialytic weight gain; SBP; systolic blood pressure; DBP: diastolic blood pressure; CRE: creatinine; ALB: albumin; CRP: C-reactive protein; CA: calcium; P: phosphate; PTH: parathyroid hormone; Na: sodium; Mg: magnesium; K: potassium; CO₂: carbon dioxide; GLU: glucose; TG: triglyceride; β₂-MG: β₂-microglobulin; β₂-MG RR; β₂-microglobulin reduction ratio; HB: hemoglobin; LTI: lean tissue index; BMI: body Mass Index; LVEF: left ventricular ejection fraction.

Figure 4. A. Subgroup analyses for the relationship of eBFR and all-cause mortality in patients according to age, sex, BMI, diabetes, CVD, HDF ≥ 1/week, and ALB. BMI, body mass index; CVD, cardiovascular disease; HDF, hemodiafiltration; ALB, albumin; HR, hazard ratio; CI confidence interval. B. Subgroup analyses for the relationship of eBFR and new MACE in patients according to age, sex, BMI, diabetes, CVD, HDF ≥ 1/week, and ALB. BMI, body mass index; CVD, cardiovascular disease; HDF, hemodiafiltration; ALB, albumin; HR, hazard ratio; CI confidence interval.

Table 5. The outcome of AVF in two groups based on the time-averaged eBFR.

		eBFR ≤ 275 mL/min	eBFR > 275 mL/min	P
N (%)	175	87 (49.7%)	88 (50.3%)	–
Type
Forearm	89.7%	92.0%	87.5%	0.701
Wrist	6.3%	4.6%	8.0%	0.701
Upperarm	4.0%	3.4%	4.5%	0.701
Complication
Thrombosis	9.1%	10.3%	8.0%	0.611
Stenosis	24.0%	27.6%	20.5%	0.293
Aneurysmal dilation	1.1%	1.1%	1.1%	1.00
Surgical intervention
Open	16.6%	16.1%	17.0%	1.000
PTA	9.7%	12.6%	6.8%	0.213
Outcome
Final AVF failure	8.6%	10.3%	6.8%	0.432

PTA: percutaneous angioplasty; AVF: arteriovenous fistula.