The baseline characteristics of critical patients with AIS based on propensity score matching (1:1) were shown in Table 1. A total of 634 critical patients with AIS aged ≥ 18 years were included in the the present study, including 354 (55.8%) males and 280 (44.2%) females, with a mean (SD) age of 69.92 (13.41) years. Compared with the No-AKI critical patients, the AKI critical patients were more likely to be older (mean [SD], 71.55 [12.15] vs 68.29 [14.39]; P-value = 0.002), have higher levels of heart rate (mean [SD], 87.57 [14.49] vs 85.14 [13.86]; P-value = 0.031), PaCO2 (mean [SD], 42.80 [8.22] vs 39.53 [6.25]; P-value < 0.001), serum lactate level (Median [IQR], 2.2 [1.5, 3.6] vs 1.6 [1.1, 2.2]; P-value < 0.001), WBC count (mean [SD], 13.29 [5.72] vs 11.54 [4.39]; P-value < 0.001), glucose (mean [SD], 172.48 [57.50] vs 138.35 [46.91]; P-value < 0.001), Scr (Median [IQR], 1.30 [0.90, 2.10] vs 0.90 [0.70, 1.20]; P-value < 0.001), potassium (mean [SD], 4.35 [0.79] vs 4.09 [0.65]; P-value < 0.001), APTT (Median [IQR], 36.00 [29.70, 48.40] vs 29.50 [25.70, 36.40]; P-value < 0.001), PT (mean [SD], 16.08 [2.45] vs 14.16 [2.16]; P-value < 0.001), INR (mean [SD], 1.50 [0.32] vs 1.27 [0.28]; P-value < 0.001), Saps II score (Median [IQR], 48.00 [41.00, 59.00] vs 32.00 [25.00, 42.00]; P-value < 0.001), SOFA score (Median [IQR], 8.00 [5.00, 10.00] vs 3.00 [1.00, 5.00]; P-value < 0.001), have lower levels of respiration rate (mean [SD], 17.07 [4.59] vs 18.23 [4.35]; P-value = 0.001), Hb (mean [SD], 9.99 [2.25] vs 11.30 [2.03]; P-value = 0.001), sodium (mean [SD], 137.84 [4.38] vs 138.58 [3.99]; P-value = 0.027), TC (Median [IQR], 145.70 [128.00, 160.70] vs 154.12 [141.00, 172.30]; P-value < 0.001), TG (Median [IQR], 127.00 [93.60, 159.00] vs 135.80 [100.40, 172.00]; P-value < 0.001), and HDL-C (Median [IQR], 37.80 [32.00, 44.00] vs 43.70 [37.00, 52.40]; P-value < 0.001), and have combination of AMI (33.1% vs 16.4%; P-value < 0.001), hypertension (48.6% vs 64.7%; P-value < 0.001), DM (56.5% vs 32.5%; P-value < 0.001), and thrombolytic agent (5% vs 11%; P-value = 0.009). There were no significant differences in sex, race, admission type, marital status, SBP, DBP, PaO2, SpO2, LDL-C, and hyperlipidemia between the two groups. In addition, the baseline characteristics of critical patients with AIS before propensity score matching are shown in Table S1.
Table 1
Baseline characteristic of all participants based on propensity score matching.
|
Overall
|
No-AKI
|
AKI
|
P-value
|
N = 634
|
N = 317
|
N = 317
|
Age, year
|
69.92 (13.41)
|
68.29 (14.39)
|
71.55 (12.15)
|
0.002
|
Gender (Female), n (%)
|
280 (44.2)
|
151 (47.6)
|
129 (40.7)
|
0.093
|
Ethnicity, n (%)
|
|
|
|
0.087
|
White
|
488 (77.0)
|
236 (74.4)
|
252 (79.5)
|
|
Black
|
37 (5.8)
|
23 (7.3)
|
14 (4.4)
|
|
Hispanic
|
21 (3.3)
|
14 (4.4)
|
7 (2.2)
|
|
Asian
|
9 (1.4)
|
7 (2.2)
|
2 (0.6)
|
|
Other
|
79 (12.5)
|
37 (11.7)
|
42 (13.2)
|
|
Admission type, n (%)
|
|
|
0.209
|
Elective
|
83 (13.1)
|
49 (15.5)
|
34 (10.7)
|
|
Emergency
|
533 (84.1)
|
259 (81.7)
|
274 (86.4)
|
|
Urgent
|
18 (2.8)
|
9 (2.8)
|
9 (2.8)
|
|
Married, n (%)
|
324 (51.1)
|
163 (51.4)
|
161 (50.8)
|
0.937
|
Vital signs, mean (SD) or Median (IQR)
|
|
|
|
Heart rate (bpm)
|
86.36 (14.22)
|
85.14 (13.86)
|
87.57 (14.49)
|
0.031
|
Respiration rate (bpm)
|
17.65 (4.51)
|
18.23 (4.35)
|
17.07 (4.59)
|
0.001
|
Systolic blood pressure (mmHg)
|
131.77 (24.59)
|
130.55 (22.39)
|
132.98 (26.59)
|
0.215
|
Diastolic blood pressure (mmHg)
|
67.89 (14.44)
|
67.85 (12.89)
|
67.94 (15.86)
|
0.934
|
PaO2 (mmHg)
|
198.95 (137.30, 283.60)
|
200.40 (144.80, 271.70)
|
198.50 (129.90, 304.00)
|
0.97
|
PaCO2 (mmHg)
|
41.17 (7.48)
|
39.53 (6.25)
|
42.80 (8.22)
|
< 0.001
|
SpO2 (%)
|
98.03 (2.37)
|
97.93 (2.23)
|
98.13 (2.49)
|
0.303
|
Laboratory tests, mean (SD) or Median (IQR)
|
|
|
Lactate acid (mmol/L)
|
1.8 (1.3, 2.8)
|
1.6 (1.1, 2.2)
|
2.2 (1.5, 3.6)
|
< 0.001
|
WBC count (×109)
|
12.42 (5.17)
|
11.54 (4.39)
|
13.29 (5.72)
|
< 0.001
|
Hb (g/L)
|
10.65 (2.24)
|
11.30 (2.03)
|
9.99 (2.25)
|
< 0.001
|
Glucose, mg/dL
|
155.41 (55.14)
|
138.35 (46.91)
|
172.48 (57.50)
|
< 0.001
|
Scr (mg/dL)
|
1.10 (0.80, 1.58)
|
0.90 (0.70, 1.20)
|
1.30 (0.90, 2.10)
|
< 0.001
|
Sodium (mmol/L)
|
138.21 (4.20)
|
138.58 (3.99)
|
137.84 (4.38)
|
0.027
|
Potassium (mmol/L)
|
4.22 (0.73)
|
4.09 (0.65)
|
4.35 (0.79)
|
< 0.001
|
APTT (seconds)
|
32.15 (27.00, 41.40)
|
29.50 (25.70, 36.40)
|
36.00 (29.70, 48.40)
|
< 0.001
|
PT (seconds)
|
15.12 (2.50)
|
14.16 (2.16)
|
16.08 (2.45)
|
< 0.001
|
INR
|
1.39 (0.32)
|
1.27 (0.28)
|
1.50 (0.32)
|
< 0.001
|
TC (mg/dL)
|
149.50 (135.00, 166.00)
|
154.12 (141.00, 172.30)
|
145.70 (128.00, 160.70)
|
< 0.001
|
TG (mg/dL)
|
130.20 (96.70, 167.12)
|
135.80 (100.40, 172.00)
|
127.00 (93.60, 159.00)
|
0.040
|
HDL-C (mg/dL)
|
40.10 (34.00, 48.00)
|
43.70 (37.00, 52.40)
|
37.80 (32.00, 44.00)
|
< 0.001
|
LDL-C (mg/dL)
|
80.80 (68.00, 93.98)
|
80.80 (67.00, 94.20)
|
80.80 (68.80, 93.50)
|
0.860
|
Complications, n (%)
|
|
|
|
|
Hyperlipidemia
|
293 (46.2)
|
152 (47.9)
|
141 (44.5)
|
0.426
|
Hypertension
|
359 (56.6)
|
205 (64.7)
|
154 (48.6)
|
< 0.001
|
AMI
|
157 (24.8)
|
52 (16.4)
|
105 (33.1)
|
< 0.001
|
DM
|
282 (44.5)
|
103 (32.5)
|
179 (56.5)
|
< 0.001
|
Thrombolytic agent, n (%)
|
51 (8.0)
|
35 (11.0)
|
16 (5.0)
|
0.009
|
Saps II score (IQR)
|
41.50 (31.00, 52.00)
|
32.00 (25.00, 42.00)
|
48.00 (41.00, 59.00)
|
< 0.001
|
SOFA score (IQR)
|
5.00 (3.00, 8.00)
|
3.00 (1.00, 5.00)
|
8.00 (5.00, 10.00)
|
< 0.001
|
Abbreviation: SpO2, pulse oxygen saturation; PaO2, partial pressure of oxygen; PaCO2, partial pressure of carbon dioxide; WBC, white blood cell; Hb, hemoglobin; Scr, serum creatinine; PT, prothrombin time; APTT, activated partial thromboplastin time; INR, international normalized ratio; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; AMI, acute myocardial infarction; DM, diabetes mellitus; SAPS, simplified acute physiology score; SOFA, sequential organ failure assessment; AKI, acute kidney injury; SD, standard deviation; IQR; interquartile range. |
As shown in Fig. 1, we performed an RCS plot to assess the association between AKI and serum lactate level, as well as the association between serum lactate level and serum glucose, and revealed a linear association of between serum lactate levels and AKI and between serum glucose levels and serum lactate levels (all P for nonlinear < 0.001). Table 2 displays the association between AKI and serum lactate level and the association between serum lactate level and serum glucose in models 1, 2, and 3, respectively. After full adjustment for potential confounders (Model 3), serum glucose was positively correlated to serum lactate level (β = 0.004, 95% CI: 0.003–0.006, P-value < 0.001). High lactate level increased the risk of AKI (OR, 2.216; 95% CI, 1.559–3.271; P-value < 0.001). The above relationship was also found in stepwise logistic regression analysis (Table S2-S3). Similarly, the association between AKI and serum lactate level and the association between serum lactate level and serum glucose was also present in subgroups age, sex, hyperlipidemia, hypertension, AMI, DM, and thrombolytic agent (Table S4). After converting serum glucose and serum lactate from a continuous variable to a categorical variable (quartiles), The corresponding β and 95% confidence interval (CI) of both the second, third, and forth quartile of serum glucose for serum lactate level were 0.083 (95% CI, -0.153-0.319), 0.259 (95% CI, 0.014–0.503) and 0.531 (95% CI, 0.272–0.790) compared with the first quartile. The corresponding odds ratio (OR) and 95% CI of both the second, third, and forth quartile of serum lactate for incidence of AKI were 1.709 (95% CI, 0.577–5.161), 5.663 (95% CI, 1.770-19.815) and 12.172 (95% CI, 3.857–42.485) compared with the first quartile (all P for trend < 0.001) (Table 2).
Table 2
The relationship of between AKI and serum lactate level and between serum lactate level and serum glucose level.
|
Model 1
|
Model 2
|
Model 3
|
|
Beta/OR (95% CI)
|
P-value
|
Beta/OR (95% CI)
|
P-value
|
Beta/OR (95% CI)
|
P-value
|
Lactate acid-glucose
|
Glucose
|
0.005(0.003, 0.006)
|
< 0.001
|
0.004(0.002,0.005)
|
< 0.001
|
0.004(0.003, 0.006)
|
< 0.001
|
Interquartile of glucose
|
|
|
|
|
|
|
Q1
|
Ref.
|
|
Ref.
|
|
Ref.
|
|
Q2
|
0.138(-0.114,0.390)
|
0.284
|
0.073(-0.167,0.312)
|
0.552
|
0.083(-0.153,0.319)
|
0.492
|
Q3
|
0.459(0.205,0.713)
|
< 0.001
|
0.256(0.011,0.502)
|
0.040
|
0.259(0.014,0.503)
|
0.038
|
Q4
|
0.613(0.360,0.867)
|
< 0.001
|
0.475(0.223,0.726)
|
< 0.001
|
0.531(0.272,0.790)
|
< 0.001
|
P for trend
|
|
< 0.001
|
|
< 0.001
|
|
< 0.001
|
AKI-lactate acid
|
lactate acid
|
1.724(1.467,2.040)
|
< 0.001
|
1.858(1.466,2.387)
|
< 0.001
|
2.216(1.559,3.271)
|
< 0.001
|
Interquartile of lactate acid
|
|
|
|
|
|
Q1
|
Ref.
|
|
Ref.
|
|
Ref.
|
|
Q2
|
1.867(1.150,3.043)
|
0.012
|
2.016(0.998,4.115)
|
0.052
|
1.709(0.577,5.161)
|
0.335
|
Q3
|
1.961(1.231,3.141)
|
0.005
|
2.576(1.282,5.276)
|
0.009
|
5.663(1.770,19.815)
|
0.005
|
Q4
|
4.705(2.873,7.822)
|
< 0.001
|
6.533(3.099,14.228)
|
< 0.001
|
12.172(3.857,42.485)
|
< 0.001
|
P for trend
|
|
< 0.001
|
|
< 0.001
|
|
< 0.001
|
Interquartile of glucose: Q1: 48–113 mg/dl; Q2: 113–140 mg/dl; Q3: 140–188 mg/dl; Q4: 188–267 mg/dl. |
Interquartile of lactate acid: Q1: 0.5–1.3 mmol/L; Q2: 1.3–1.8 mmol/L; Q3: 1.8–2.8 mmol/L; Q4: 2.8–4.7 mmol/L. |
Model 1 adjusted for age, sex, ethnicity, admission type, married. |
Model 2 adjusted for age, sex, ethnicity, admission type, married, HR, RR, PaO2, PaCO2, SpO2, Systolic blood pressure, diastolic blood pressure, WBC, Hb, SCr, sodium, potassium, APTT, PT, INR, TC, TG, HDL-C, LDL-C. |
Model 3 adjusted for age, sex, ethnicity, admission type, married, HR, RR, PaO2, PaCO2, SpO2, Systolic blood pressure, diastolic blood pressure, WBC, Hb, SCr, sodium, potassium, APTT, PT, INR, TC, TG, HDL-C, LDL-C, hyperlipidemia, hypertension, AMI, DM, thrombolytic agent, SAPS II score, SOFA score. |
Abbreviation: SpO2, pulse oxygen saturation; PaO2, partial pressure of oxygen; PaCO2, partial pressure of carbon dioxide; WBC, white blood cell; Hb, hemoglobin; Scr, serum creatinine; PT, prothrombin time; APTT, activated partial thromboplastin time; INR, international normalized ratio; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; AMI, acute myocardial infarction; DM, diabetes mellitus; SAPS, simplified acute physiology score; SOFA, sequential organ failure assessment; AKI, acute kidney injury. |
More importantly, we performed the mediation analysis of serum glucose for association between serum lactate level and AKI. After adjusting for the confounding factors, we found that serum glucose was involved in the process of serum lactate level -related AKI to some extent. serum glucose explains 14.9% of the association between serum lactate and AKI among critical patients with AIS (P-value < 0.001) (Fig. 2A), serum glucose explains 16.4% of the association between serum lactate and AKI among critical patients with AIS and with DM (P-value = 0.24) (Fig. 2B), and serum glucose explains 19.5% of the association between serum lactate and AKI among critical patients with AIS and without DM (P-value < 0.001) (Fig. 2C). However, no statistical significance among critical patients with AIS and with DM was observed (Fig. 2 and Figure S1-S3). Therefore, the above results suggest that serum lactate level have a linear association with AKI, and this relationship is mediated by serum glucose some to extent.