Nonlinear association between estimated plasma volume status and acute kidney injury in acute pancreatitis patients

Table 1 Baseline characteristics of included patients grouped by occurrence of acute kidney injury, mean ± SD/n (%)

Variables	Non-AKI (n = 1257)	AKI (n = 251)	P value
Male	642 (51.1)	164 (65.3)	< 0.001
Age (years), median (IQR)	53.0 (41.0, 64.0)	56.0 (44.0, 69.0)	0.002
Hypertension	304 (24.2)	88 (35.1)	< 0.001
DM	177 (14.1)	47 (18.7)	0.059
CHD	77 (6.1)	26 (10.4)	0.015
COPD	48 (3.8)	15 (6)	0.119
Weight (kg), median (IQR)	64.0 (56.0, 75.0)	66.0 (55.0, 75.0)	0.675
Height (cm), median (IQR)	163.0 (158.0, 170.0)	166.0 (158.0, 172.0)	0.003
BMI (kg/m2), median (IQR)	24.1 (21.8, 26.7)	24.2 (20.9, 26.9)	0.534
HR (bpm), median (IQR)	78.0 (72.0, 90.0)	90.0 (76.0, 109.5)	< 0.001
SBP (mmHg), median (IQR)	130.0 (119.0, 143.0)	123.0 (110.0, 140.5)	< 0.001
DBP (mmHg), median (IQR)	80.0 (74.0, 90.0)	80.0 (66.0, 89.0)	0.001
RR (bpm), median (IQR)	20.0 (19.0, 20.0)	20.0 (19.0, 21.0)	0.010
SpO2 (%), median (IQR)	99.0 (98.0, 100.0)	98.0 (96.0, 100.0)	< 0.001
Mechanical ventilation	73 (5.8)	83 (33.1)	< 0.001
Transfusion	70 (5.6)	93 (37.1)	< 0.001
CRRT	21 (1.7)	66 (26.3)	< 0.001
WBC (× 109/L), median (IQR)	9.6 (6.4, 13.2)	11.2 (7.8, 15.8)	< 0.001
HGB (g/L), median (IQR)	129.0 (116.0, 144.0)	128.0 (106.0, 150.5)	0.255
HCT (%), median (IQR)	38.7 (34.9, 42.3)	37.6 (32.2, 43.2)	0.057
PLT (× 109/L), median (IQR)	181.0 (139.0, 234.0)	172.0 (111.0, 226.5)	0.005
PCT (ng/mL), median (IQR)	0.1 (0.0, 0.6)	1.1 (0.2, 6.2)	< 0.001
CRP (mg/L), median (IQR)	31.4 (5.9, 119.0)	90.8 (17.2, 198.6)	< 0.001
AST (U/L), median (IQR)	41.0 (23.0, 143.0)	44.0 (25.0, 132.5)	0.422
ALB (g/dL), median (IQR)	39.1 (34.9, 42.7)	34.9 (28.6, 39.7)	< 0.001
FPG (mmol/L), median (IQR)	6.6 (5.3, 8.9)	7.5 (5.7, 11.2)	< 0.001
AMY (U/L), median (IQR)	163.0 (64.5, 716.0)	193.0 (90.0, 580.0)	0.124
TG (mmol/L), median (IQR)	1.5 (1.0, 3.4)	1.8 (1.2, 6.4)	< 0.001
Na+ (mmol/L), median (IQR)	139.7 (137.1, 141.8)	137.9 (135.0, 141.1)	< 0.001
Ca2+ (mmol/L), median (IQR)	2.2 (2.1, 2.4)	2.1 (1.9, 2.3)	< 0.001
BUN (mmol/L), median (IQR)	5.0 (3.8, 6.3)	9.6 (5.9, 15.1)	< 0.001
CREA (mmol/L), median (IQR)	71.0 (59.0, 83.0)	95.5 (84.0, 187.0)	< 0.001
D-ePVS (dL/g), median (IQR)	4.7 (4.0, 5.6)	4.9 (3.8, 6.4)	0.181
KH-ePVS (%), median (IQR)	-2.5 (-10.0, 4.5)	0.9 (-10.7, 13.1)	0.002
Death	5 (0.4)	18 (7.2)	< 0.001
LOS (day), median (IQR)	13.0 (10.0, 18.0)	16.0 (10.0, 26.0)	< 0.001
ICU	115 (9.1)	127 (50.6)	< 0.001
SOFA (score)	2.2 ± 1.9	5.0 ± 3.6	< 0.001
BISAP (score)	1.2 ± 1.1	2.0 ± 1.3	< 0.001
Biliary	887 (70.6)	130 (51.8)
Hyperlipidemic	289 (23)	64 (25.5)
Alcoholic	42 (3.3)	8 (3.2)
Others	39 (3.1)	49 (19.5)
Severity of AP (%)			< 0.001
Mild and moderate	800 (63.6)	90 (35.9)
Severe	457 (36.4)	161 (64.1)

IQR: Interquartile range; AKI: Acute kidney injury; DM: Diabetes mellitus; CHD: Coronary heart disease; COPD: Chronic obstructive pulmonary disease; BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HR: Heart rate; RR: Respiratory rate; SpO₂: Pulse oxygen saturation; CRRT: Continuous renal replacement treatment; WBC: White blood cell count; HGB: Hemoglobin; HCT: Hematocrit; PCT: Procalcitonin; CRP: C-reactive protein; PLT: Platelet; AST: Aspartate aminotransferase; ALB: Albumin; AMY: Amylase; FPG: Fasting plasma glucose; TG: Triglyceride; Na⁺: Sodium; Ca²⁺: Calcium; BUN: Blood urea nitrogen; CREA: Creatinine; D-ePVS: Duarte formula-based estimated plasma volume status; KH-ePVS: Kaplan-Hakim formula-based estimated plasma volume status; ICU: Intensive care unit; LOS: Length of hospital stay; SOFA: Sequential organ failure assessment score; BISAP: Bedside index of severity in acute pancreatitis score; AP: Acute pancreatitis; Mechanical ventilation: Noninvasive or invasive mechanical ventilation; Transfusion: Blood transfusion.

Table 2 Baseline characteristics of included patients grouped by tertile of estimated plasma volume status using Duarte and Kaplan-Hakim formula, mean ± SD/n (%)

Characteristics	D-ePVS formula				KH-ePVS formula
	T1 (n = 505) (< 4.231 dL/g)	T2 (n = 504) (4.231-5.358 dL/g)	T3 (n = 505) (≥ 5.358 dL/g)	P value	T1 (n = 505) (< -7.425)	T2 (n = 504) (-7.425-2.669)	T3 (n = 505) (≥ 2.669)	P value
Male	401 (79.7)	239 (47.6)	166 (33)	< 0.001	363 (72.2)	211 (42)	232 (46.1)	< 0.001
Age (years), median (IQR)	46.0 (36.0, 57.0)	55.0 (44.0, 65.0)	59.0 (48.0, 69.0)	< 0.001	45.0 (35.0, 56.0)	54.0 (46.0, 66.0)	60.0 (50.0, 70.0)	< 0.001
Death	9 (1.8)	2 (0.4)	12 (2.4)	0.031	493 (98)	500 (99.6)	492 (97.8)	0.04
ICU	75 (14.9)	51 (10.2)	116 (23.1)	< 0.001	75 (14.9)	51 (10.2)	116 (23.1)	< 0.001
LOS (day), median (IQR)	12.0 (10.0, 17.0)	13.0 (10.0, 18.0)	14.0 (10.0, 22.0)	< 0.001	12.0 (10.0, 17.0)	12.0 (10.0, 18.0)	14.0 (10.0, 23.0)	< 0.001
Hypertension	119 (23.7)	132 (26.3)	141 (28)	0.281	118 (23.5)	149 (29.7)	125 (24.9)	0.062
DM	85 (16.9)	62 (12.4)	77 (15.3)	0.121	95 (18.9)	60 (12)	69 (13.7)	0.006
CHD	477 (94.8)	473 (94.2)	455 (90.5)	0.012	26 (5.2)	32 (6.4)	45 (8.9)	0.053
SBP (mmHg), median (IQR)	130.0 (120.0, 144.0)	130.0 (118.0, 144.0)	125.0 (112.0, 140.0)	< 0.001	130.0 (120.0, 146.0)	130.0 (118.0, 142.0)	125.0 (111.0, 140.0)	< 0.001
DBP (mmHg), median (IQR)	85.0 (78.0, 94.0)	80.0 (72.0, 90.0)	78.0 (69.0, 85.5)	< 0.001	86.0 (78.0, 95.0)	80.0 (72.0, 90.0)	77.0 (69.0, 85.0)	< 0.001
HR (bpm), median (IQR)	82.0 (75.0, 100.0)	78.0 (72.0, 90.0)	80.0 (72.0, 92.0)	< 0.001	82.0 (75.0, 99.0)	78.0 (72.0, 89.8)	80.0 (72.0, 94.0)	< 0.001
RR (bpm), median (IQR)	20.0 (19.0, 20.0)	20.0 (19.0, 20.0)	20.0 (18.0, 20.0)	0.002	20.0 (19.0, 20.0)	20.0 (19.0, 20.0)	20.0 (18.0, 20.0)	< 0.001
SpO2 (%), median (IQR)	99.0 (97.0, 100.0)	99.0 (97.0, 100.0)	99.0 (98.0, 100.0)	0.464	99.0 (97.0, 100.0)	99.0 (97.0, 100.0)	99.0 (97.0, 100.0)	0.318
Mechanical ventilation (%)	52 (10.3)	37 (7.4)	67 (13.3)	0.008	46 (9.1)	31 (6.2)	79 (15.7)	< 0.001
Transfusion (%)	41 (8.2)	30 (6)	92 (18.3)	< 0.001	35 (7)	27 (5.4)	101 (20.1)	< 0.001
CRRT (%)	38 (7.6)	12 (2.4)	37 (7.4)	< 0.001	37 (7.4)	12 (2.4)	38 (7.6)	< 0.001
WBC (× 109/L), median (IQR)	11.9 (8.4, 15.2)	9.6 (6.5, 12.8)	8.3 (5.6, 11.9)	< 0.001	11.8 (8.5, 14.8)	9.3 (6.5, 12.9)	8.3 (5.6, 12.3)	< 0.001
HGB (g/L), median (IQR)	152.0 (144.0, 162.0)	129.0 (125.0, 134.0)	108.0 (98.0, 114.0)	< 0.001	151.0 (141.0, 161.0)	128.0 (120.0, 136.0)	109.0 (98.0, 119.0)	< 0.001
HCT (%), median (IQR)	44.5 (42.5, 47.2)	38.6 (37.2, 40.0)	32.8 (30.0, 34.6)	< 0.001	44.3 (42.0, 47.2)	38.0 (36.4, 40.1)	33.0 (30.0, 35.6)	< 0.001
PCT (ng/mL), median (IQR)	0.2 (0.1, 0.9)	0.1 (0.0, 0.6)	0.3 (0.1, 1.2)	< 0.001	0.2 (0.1, 0.7)	0.1 (0.0, 0.5)	0.3 (0.1, 1.4)	< 0.001
CRP (mg/L), median (IQR)	37.3 (7.3, 130.7)	27.4 (4.1, 123.2)	53.3 (7.6, 139.0)	0.007	34.7 (7.1, 138.1)	32.8 (5.3, 134.7)	45.9 (7.2, 133.4)	0.194
AST (U/L), median (IQR)	38.0 (23.2, 121.5)	44.2 (24.0, 152.5)	41.0 (22.0, 143.5)	0.435	38.0 (23.0, 134.0)	42.0 (22.7, 143.8)	42.0 (22.0, 137.4)	0.919
ALB (g/dL), median (IQR)	41.1 (37.4, 44.3)	38.9 (35.3, 42.5)	35.0 (29.6, 39.2)	< 0.001	41.4 (37.9, 44.4)	38.4 (34.9, 41.9)	35.2 (29.6, 39.4)	< 0.001
FPG (mmol/L), median (IQR)	7.5 (6.0, 11.5)	6.5 (5.3, 8.7)	6.1 (5.0, 7.8)	< 0.001	7.8 (6.0, 11.9)	6.4 (5.2, 8.4)	6.2 (5.0, 7.8)	< 0.001
TG (mmol/L), median (IQR)	2.4 (1.2, 7.7)	1.4 (0.9, 2.7)	1.3 (0.9, 2.2)	< 0.001	2.5 (1.2, 7.4)	1.4 (1.0, 2.7)	1.2 (0.9, 2.2)	< 0.001
Na+ (mmol/L), median (IQR)	138.8 (135.5, 141.1)	139.8 (137.2, 142.2)	139.9 (137.3, 141.9)	< 0.001	139.1 (135.8, 141.2)	139.9 (137.3, 142.4)	139.6 (136.9, 141.8)	< 0.001
Ca2+ (mmol/L), median (IQR)	2.3 (2.1, 2.4)	2.2 (2.1, 2.4)	2.1 (2.0, 2.3)	< 0.001	2.2 (2.1, 2.4)	2.2 (2.1, 2.4)	2.1 (2.0, 2.3)	< 0.001
AMY (U/L), median (IQR)	236.0 (85.0, 875.5)	193.0 (68.3, 650.8)	117.0 (59.0, 433.0)	< 0.001	251.0 (78.2, 921.0)	182.7 (68.3, 574.0)	128.0 (60.0, 466.0)	< 0.001
CREA (μmol/L), median (IQR)	80.0 (69.0, 92.0)	71.1 (59.0, 84.1)	71.0 (58.0, 88.0)	< 0.001	79.0 (67.0, 91.0)	70.0 (58.7, 81.8)	75.0 (60.0, 90.0)	< 0.001
AKI	91 (18.1)	55 (11)	105 (20.9)	< 0.001	81 (16.1)	62 (12.4)	108 (21.5)	< 0.001
Etiology				< 0.001				< 0.001
Biliary	276 (54.9)	367 (73.1)	374 (74.4)		272 (54.1)	372 (74.1)	373 (74.2)
Hyperlipidemic	186 (37)	97 (19.3)	70 (13.9)		189 (37.6)	99 (19.7)	65 (12.9)
Alcoholic	28 (5.6)	13 (2.6)	9 (1.8)		29 (5.8)	12 (2.4)	9 (1.8)
Others	13 (2.6)	25 (5)	50 (9.9)		13 (2.6)	19 (3.8)	56 (11.1)
SOFA (score)	2.5 ± 2.4	2.5 ± 2.2	3.1 ± 2.8	< 0.001	2.4 ± 2.2	2.5 ± 2.2	3.2 ± 2.9	< 0.001
BISAP (score)	1.3 ± 1.1	1.2 ± 1.2	1.4 ± 1.2	0.004	1.3 ± 1.1	1.2 ± 1.1	1.5 ± 1.2	< 0.001
Severity of AP				0.006				< 0.001
Mild and moderate	434 (86.3)	467 (93.0)	439 (87.3)		442 (87.9)	472 (94.0)	426 (84.7)
Severe	69 (13.7)	35 (7.0)	64 (12.7)		61 (12.1)	30 (6.0)	77 (15.3)

IQR: Interquartile range; D-ePVS: Duarte formula-based estimated plasma volume status; KH-ePVS: Kaplan-Hakim formula-based estimated plasma volume status; ICU: Intensive care unit; LOS: Length of hospital stay; DM: Diabetes mellitus; CHD: Coronary heart disease; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HR: Heart rate; RR: Respiratory rate; SpO₂: Pulse oxygen saturation; CRRT: Continuous renal replacement treatment; WBC: White blood cell count; HGB: Hemoglobin; HCT: Hematocrit; PCT: Procalcitonin; CRP: C-reactive protein; AST: Aspartate aminotransferase; ALB: Albumin; FPG: Fasting plasma glucose; TG: Triglyceride; Na⁺: Sodium; Ca²⁺: Calcium; AMY: Amylase; CREA: Creatinine; AKI: Acute kidney injury; SOFA: Sequential organ failure assessment score; BISAP: Bedside index of severity in acute pancreatitis score; AP: Acute pancreatitis.

Table 3 Multiple logistic regression analysis for estimated plasma volume status and acute kidney injury in acute pancreatitis population

	Non-adjusted model		Adjusted model 1		Adjusted model 2		Adjusted model 3
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
D-ePVS, tertiles
T1	1.8 (1.25-2.57)	0.001	1.65 (1.13-2.41)	0.01	1.54 (1.04-2.29)	0.032	1.56 (1.01-2.41)	0.045
T2	Ref.		Ref.		Ref.		Ref.
T3	2.14 (1.51-3.05)	< 0.001	2.32 (1.61-3.35)	< 0.001	2.31 (1.57-3.38)	< 0.001	1.87 (1.2-2.91)	0.005
P for trend	0.236		0.043		0.028		0.469
KH-ePVS, tertiles
T1	1.36 (0.95-1.95)	0.089	1.28 (0.87~1.89)	0.211	1.18 (0.79-1.77)	0.414	1.11 (0.72-1.72)	0.629
T2	Ref.		Ref.		Ref.		Ref.
T3	1.94 (1.38-2.73)	< 0.001	1.83 (1.28-2.62)	0.001	1.4 (1.19-2.54)	0.004	1.51 (1-2.29)	0.05
P for trend	0.023		0.051		0.05		0.167

Kaplan-Hakim formula-based estimated plasma volume status of tertile 1: < -7.425; tertile 2: -7.425 to 2.669; tertile 3: ≥ 2.669. Duarte formula-based estimated plasma volume status of tertile 1: < 4.231; tertile 2: 4.231-5.358; tertile 3: ≥ 5.358. Model 1: Adjusted for age, sex and body mass index. Model 2: Adjusted for age, sex, body mass index, hypertension, diabetes mellitus, coronary heart disease, heart rate, respiratory rate and pulse oxygen saturation. Model 3: Adjusted for age, sex, hypertension, diabetes mellitus, coronary heart disease, heart rate, respiratory rate, pulse oxygen saturation, sequential organ failure assessment score, bedside index of severity in acute pancreatitis score, triglyceride, calcium, albumin, fasting plasma glucose, amylase, procalcitonin, C-reactive protein and white blood cell count. D-ePVS: Duarte formula-based estimated plasma volume status; KH-ePVS: Kaplan-Hakim formula-based estimated plasma volume status; OR: Odds ratio; CI: Confidence interval.

Table 4 Threshold effect analysis of estimated plasma volume status and acute kidney injury using two-piecewise regression models

Two-piecewise linear regression model	D-ePVS		KH-ePVS
	OR (95%CI)	P value	OR (95%CI)	P value
Inflection point (K)	4.3		-2.8
ePVS < K	0.579 (0.335-0.998)	0.049	0.990 (0.953-1.028)	0.601
ePVS ≥ K	1.235 (1.079-1.413)	0.002	1.032 (1.005-1.06)	0.019
Likelihood ratio test		0.002		0.006
Non-linear test		0.021		0.025

Adjusted for all covariates as model 3. ePVS: Estimated plasma volume status; D-ePVS: Duarte formula-based estimated plasma volume status; KH-ePVS: Kaplan-Hakim formula-based estimated plasma volume status; OR: Odds ratio; CI: Confidence interval.