Elevated mean arterial pressure is associated with a lower risk of mortality in acute kidney injury patients receiving continuous renal replacement therapy

Figures & data

Table 1. Baseline characteristics of the four groups.

Variables	Total	Quartile 1	Quartile 2	Quartile 3	Quartile 4	p Value
N	1144	283	295	278	288
Age (years), median (IQR)	66.0 (54.0, 74.0)	69.0 (56.0, 75.0)	66.0 (55.5, 73.0)	65.0 (54.2, 73.0)	63.0 (52.0, 72.0)	0.002
Male, yes (%)	705 (61.6)	173 (61.1)	172 (58.3)	170 (61.2)	190 (66)	0.292
BMI, (kg/m^2), median (IQR)	23.6 (20.9, 26.2)	23.5 (20.7, 25.9)	23.7 (21.1, 26.5)	23.4 (20.9, 26.1)	23.7 (20.9, 26.5)	0.725
SBP, (mmHg), median (IQR)	110.0 (97.0, 125.0)	92.0 (86.0, 100.0)	106.0 (99.0, 114.5)	113.0 (104.0, 122.0)	134.0 (122.8, 145.0)	< 0.001
DBP, (mmHg), median (IQR)	60.0 (50.0, 70.0)	45.0 (40.0, 50.0)	55.0 (51.0, 61.0)	65.0 (59.0, 69.0)	75.0 (69.0, 82.0)	< 0.001
Myocardial infarction, yes (%)	112 (9.8)	26 (9.2)	33 (11.2)	25 (9)	28 (9.7)	0.809
Heart failure, yes (%)	186 (16.3)	48 (17)	43 (14.6)	51 (18.3)	44 (15.3)	0.613
Cerebrovascular disease, yes (%)	114 (10.0)	16 (5.7)	29 (9.8)	32 (11.5)	37 (12.8)	0.031
PVD, yes (%)	46 (4.0)	10 (3.5)	12 (4.1)	11 (4)	13 (4.5)	0.948
Dementia, yes (%)	42 (3.7)	14 (4.9)	6 (2)	10 (3.6)	12 (4.2)	0.291
Diabetes mellitus, yes (%)	398 (34.8)	92 (32.5)	108 (36.6)	93 (33.5)	105 (36.5)	0.642
Hypertension, yes (%)	601 (52.5)	144 (50.9)	146 (49.5)	148 (53.2)	163 (56.6)	0.339
MV (%)	898 (78.6)	237 (84)	232 (78.6)	212 (76.3)	217 (75.3)	0.053
COPD, yes (%)	80 (7.0)	19 (6.7)	18 (6.1)	18 (6.5)	25 (8.7)	0.621
Cause of CRRT, n (%)						0.011
Volume overload	160 (14.0)	47 (16.6)	39 (13.2)	37 (13.3)	37 (12.8)
Metabolic acidosis	242 (21.2)	68 (24)	60 (20.3)	56 (20.1)	58 (20.1)
Hyperkalemia	58 (5.1)	13 (4.6)	22 (7.5)	11 (4)	12 (4.2)
Uremia	115 (10.1)	19 (6.7)	35 (11.9)	26 (9.4)	35 (12.2)
Oliguria	294 (25.7)	60 (21.2)	69 (23.4)	96 (34.5)	69 (24)
Others	275 (24.0)	76 (26.9)	70 (23.7)	52 (18.7)	77 (26.7)
AKIN stages, n (%)						0.095
Stage 2	298 (26.0)	58 (20.5)	81 (27.5)	81 (29.1)	78 (27.1)
Stage 3	846 (74.0)	225 (79.5)	214 (72.5)	197 (70.9)	210 (72.9)
Cause of AKI, n (%)						0.536
Sepsis	798 (69.8)	191 (67.5)	206 (69.8)	202 (72.7)	199 (69.1)
Nephrotoxin	37 (3.2)	6 (2.1)	9 (3.1)	8 (2.9)	14 (4.9)
Ischemia	98 (8.6)	29 (10.2)	28 (9.5)	15 (5.4)	26 (9)
Surgery	94 (8.2)	28 (9.9)	20 (6.8)	24 (8.6)	22 (7.6)
Others	117 (10.2)	29 (10.2)	32 (10.8)	29 (10.4)	27 (9.4)
Potassium (mEq/L), median (IQR)	4.5 (4.0, 5.3)	4.5 (4.1, 5.3)	4.6 (3.9, 5.3)	4.5 (3.9, 5.2)	4.5 (4.0, 5.2)	0.649
Phosphate (mg/dL), median (IQR)	5.4 (4.0, 7.0)	5.4 (4.0, 7.2)	5.5 (4.0, 7.3)	5.5 (4.2, 6.9)	5.4 (3.9, 6.6)	0.637
CCI, median (IQR)	3.0 (2.0, 5.0)	2.0 (1.0, 5.0)	2.0 (2.0, 5.0)	3.0 (2.0, 5.0)	3.0 (2.0, 5.0)	0.272
Hemoglobin (g/dL), median (IQR)	9.3 (8.2, 10.7)	9.1 (8.0, 10.6)	9.3 (8.2, 10.4)	9.3 (8.2, 10.7)	9.7 (8.4, 11.2)	0.017
White blood cell (μL)	11660 (6452, 18645)	13130 (7275, 20455)	11095 (6415, 17347)	10695 (5632, 17245)	12300 (6545, 18990)	0.093
BUN (mg/dL), median (IQR)	49.0 (33.0, 73.0)	45.0 (31.0, 71.0)	51.0 (33.5, 75.0)	51.5 (35.0, 73.0)	51.0 (35.0, 73.8)	0.252
Creatinine (mg/dL), median (IQR)	2.4 (1.6, 3.4)	2.2 (1.6, 3.5)	2.4 (1.7, 3.2)	2.4 (1.6, 3.4)	2.5 (1.7, 3.6)	0.429
Albumin (g/dL), median (IQR)	2.6 (2.2, 3.0)	2.6 (2.2, 3.0)	2.6 (2.2, 2.9)	2.6 (2.2, 3.0)	2.6 (2.2, 3.0)	0.613
CRP (mg/L), median (IQR)	78.7 (21.0, 170.8)	81.8 (26.9, 171.5)	87.8 (20.8, 189.6)	80.3 (19.5, 175.4)	64.8 (18.2, 146.0)	0.298
eGFR, median (IQR)	26.3 (17.1, 39.0)	28.8 (17.9, 41.3)	26.4 (17.3, 36.5)	25.5 (17.2, 39.9)	25.2 (16.0, 39.2)	0.382
APACHE II score, median (IQR)	28.0 (22.0, 33.0)	29.0 (24.0, 35.0)	28.0 (22.0, 33.0)	26.5 (21.0, 33.0)	27.0 (21.0, 31.0)	< 0.001
SOFA score, median (IQR)	12.0 (10.0, 14.0)	13.0 (10.0, 15.0)	12.0 (10.0, 15.0)	12.0 (9.0, 14.0)	12.0 (10.0, 14.0)	0.011
CRRT dose, median (IQR)	36.7 (34.0, 39.5)	36.5 (33.6, 39.6)	36.4 (34.0, 39.2)	37.0 (34.0, 39.6)	36.9 (34.5, 39.7)	0.365

Quartile 1: MAP < 67.3 mmHg; Quartile 2: 67.3 ≤ MAP < 76.7 mmHg; Quartile 3: 76.7 ≤ MAP < 86.3 mmHg; Quartile 4: MAP ≥ 86.3 mmHg.

MAP: Mean arterial pressure; BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; PVD: Peripheral vascular disease; MV: Mechanical ventilation; COPD: Chronic obstructive pulmonary disease; AKIN: Acute kidney injury criteria; AKI: Acute kidney injury; CCI: Charlson comorbidity index; BUN: Blood urea nitrogen; CRP: C-reactive protein; eGFR: Estimated glomerular filtration rate; APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA score: Sequential Organ Failure Assessment Score; CRRT: Continuous renal replacement therapy.

Figure 1. Comparison of 28-day (left panel) and 90-day mortality (right panel) among four groups. Quartile 1: MAP < 67.3 mmHg; Quartile 2: 67.3 ≤ MAP < 76.7 mmHg; Quartile 3: 76.7 ≤ MAP < 86.3 mmHg; Quartile 4: MAP ≥ 86.3 mmHg.

Figure 2. Kaplan–meier analysis of mean arterial pressure and 28-day (left panel) and 90-day (right panel) mortality. Quartile 1: MAP < 67.3 mmHg; Quartile 2: 67.3 ≤ MAP < 76.7 mmHg; Quartile 3: 76.7 ≤ MAP < 86.3 mmHg; Quartile 4: MAP ≥ 86.3 mmHg.

Table 2. Univariable Cox proportional hazard regression analysis associated with 28 - and 90-day mortality.

	28-day mortality		90-day mortality
Variables	HR (95% CI)	p Value	HR (95% CI)	p Value
Age	1.00 (0.99–1.01)	0.824	1.00 (0.99–1.01)	0.286
Male	0.94 (0.81–1.09)	0.420	0.98 (0.85–1.13)	0.810
BMI	0.98 (0.96–0.99)	0.024	0.98 (0.96–0.99)	0.003
SBP	0.99 (0.98–0.99)	<0.001	0.98 (0.98–0.99)	<0.001
DBP	0.98 (0.98–0.99)	<0.001	0.99 (0.98–0.99)	<0.001
Myocardial infarction	0.89 (0.69–1.15)	0.373	0.88 (0.69–1.12)	0.311
Heart failure	1.29 (1.05–1.59)	0.015	0.88 (0.73–1.06)	0.180
Cerebrovascular disease	0.84 (0.65–1.08)	0.176	0.96 (0.76–1.22)	0.762
PVD	0.82 (0.56–1.20)	0.307	0.98 (0.68–1.39)	0.898
Dementia	0.66 (0.43–1.02)	0.064	0.76 (0.51–1.14)	0.188
Diabetes mellitus	1.18 (1.01–1.38)	0.041	1.21 (1.05–1.40)	0.011
Hypertension	1.43 (1.24–1.66)	<0.001	1.33 (1.16–1.53)	<0.001
MV	1.82 (1.48–2.23)	<0.001	1.65 (1.37–1.98)	<0.001
COPD	0.81 (0.59–1.11)	0.189	0.86 (0.65–1.14)	0.290
Cause of CRRT
Volume overload	Reference	Reference	Reference	Reference
Metabolic acidosis	1.24 (1.03–1.73)	0.027	1.32 (1.04–1.68)	0.021
Hyperkalemia	1.48 (1.02–2.16)	0.037	1.40 (0.99–1.98)	0.056
Uremia	0.89 (0.65–1.23)	0.503	1.08 (0.81–1.45)	0.598
Oliguria	1.01 (0.78–1.31)	0.916	1.09 (0.86–1.37)	0.493
Others	1.25 (0.97–1.61)	0.084	1.20 (0.95–1.52)	0.127
AKIN stages	1.03 (0.87–1.21)	0.753	0.97 (0.83–1.13)	0.702
Cause of AKI
Sepsis	Reference	Reference	Reference	Reference
Nephrotoxin	0.93 (0.61–1.41)	0.717	0.88 (0.58–1.32)	0.536
Ischemia	1.06 (0.81–1.37)	0.677	1.07 (0.84–1.37)	0.569
Surgery	0.82 (0.61–1.10)	0.196	0.71 (0.54–0.93)	0.014
Others	1.34 (1.05–1.70)	0.018	0.91 (0.72–1.15)	0.446
Potassium	1.02 (0.95–1.09)	0.582	1.04 (0.98–1.11)	0.183
Phosphate	1.06 (1.03–1.09)	<0.001	1.06 (1.03–1.08)	<0.001
CCI	1.08 (1.05–1.11)	<0.001	1.07 (1.03–1.10)	<0.001
Hemoglobin	0.95 (0.92–0.98)	0.003	0.95 (0.92–0.98)	0.002
White blood cell	1.00 (1.00–1.00)	0.062	1.00 (1.00–1.00)	0.030
BUN	1.00 (0.99–1.00)	0.136	1.00 (1.00–1.00)	0.080
Creatinine	0.91 (0.87–0.96)	<0.001	0.89 (0.85–0.94)	<0.001
Albumin	0.68 (0.60–0.77)	<0.001	0.64 (0.57–0.72)	<0.001
CRP	1.00 (1.00–1.00)	0.270	1.00 (1.00–1.00)	0.329
eGFR	1.00 (1.00–1.01)	0.093	1.00 (1.00–1.00)	0.001
APACHE II score	1.03 (1.02–1.04)	<0.001	1.03 (1.02–1.04)	<0.001
SOFA score	1.17 (1.14–1.19)	<0.001	1.12 (1.09–1.14)	<0.001
CRRT dose	1.01 (0.99–1.02)	0.468	1.00 (0.99–1.02)	0.569
MAP
Quartile 1	Reference	Reference	Reference	Reference
Quartile 2	0.78 (0.64–0.95)	0.015	0.79 (0.65–0.95)	0.013
Quartile 3	0.75 (0.62–0.92)	0.006	0.77 (0.64–0.93)	0.006
Quartile 4	0.54 (0.43–0.66)	<0.001	0.58 (0.47–0.70)	<0.001

Quartile 1: MAP < 67.3 mmHg; Quartile 2: 67.3 ≤ MAP < 76.7 mmHg; Quartile 3: 76.7 ≤ MAP < 86.3 mmHg; Quartile 4: MAP ≥ 86.3 mmHg.

MAP: Mean arterial pressure; HR: hazard ratio; CI: confident interval; BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; PVD: Peripheral vascular disease; MV: Mechanical ventilation; COPD: Chronic obstructive pulmonary disease; AKIN: Acute kidney injury criteria; AKI: Acute kidney injury; CCI: Charlson comorbidity index; BUN: Blood urea nitrogen; CRP: C-reactive protein; eGFR: Estimated glomerular filtration rate; APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA score: Sequential Organ Failure Assessment Score; CRRT: Continuous renal replacement therapy.

Figure 3. Lasso regression analysis associated with 28-day mortality.

Figure 4. Lasso regression analysis associated with 90-day mortality.

Figure 5. Independent association of MAP with 28-day (left panel) and 90-day (left panel) mortality. Quartile 1: MAP < 67.3 mmHg; Quartile 2: 67.3 ≤ MAP < 76.7 mmHg; Quartile 3: 76.7 ≤ MAP < 86.3 mmHg; Quartile 4: MAP ≥ 86.3 mmHg.

Figure 6. Restricted cubic splines illustrate the outcomes, demonstrating a non-linear association between MAP and both 28-day and 90-day mortality with and without accounting for potential confounding factors. MAP: mean arterial pressure. Hypertension, continuous renal replacement therapy cause, Charlson comorbidity index, acute kidney injury cause, and phosphate were adjusted in the adjusted model of 28- mortality. Hypertension, Charlson comorbidity index, acute kidney injury cause, and phosphate were adjusted in the adjusted model of 90- mortality.

Table 3. Multivariable Cox proportional hazard regression analysis associated with 28 - and 90-day mortality.

	28-day mortality			90-day mortality
MAP	HR	95% CI	p Value	HR	95% CI	p Value
Quartile 1	Reference	Reference		Reference	Reference
Quartile 2	0.72	0.59–0.89	0.002	0.73	0.60–0.89	0.002
Quartile 3	0.69	0.56–0.85	<0.001	0.71	0.58–0.86	<0.001
Quartile 4	0.51	0.41–0.64	<0.001	0.56	0.45–0.68	<0.001

Quartile 1: MAP < 67.3 mmHg; Quartile 2: 67.3 ≤ MAP < 76.7 mmHg; Quartile 3: 76.7 ≤ MAP < 86.3 mmHg; Quartile 4: MAP ≥ 86.3 mmHg.

MAP: Mean arterial pressure; HR: hazard ratio; CI = confident interval.

Hypertension, cause of continuous renal replacement therapy, Charlson comorbidity index, cause of acute kidney injury, and phosphate were adjusted in model for 28-day mortality.

Hypertension, Charlson comorbidity index, cause of acute kidney injury, and phosphate were adjusted in model for 90-day mortality.

Data availability statement

All the data can be freely downloaded from public databases (https://datadryad.org/).