3.1. Baseline characteristics and sofa scores
We included a total of 1071 patients who met the criteria and received vancomycin, with a mean age of 62.3 ± 14.8 years. Of these, 61.8% were male. According to the TyG index, participants were divided into four groups based on quartiles(Q1: 8.40 [8.17;8.57]; Q2: 8.90 [8.79;9.02]; Q3: 9.36 [9.24;9.49]; Q4: 9.97 [9.78;10.2]), as shown in Table 1. In the Q4 group, patients tended to have a lower age but a higher BMI. Additionally, a higher proportion of patients in this group had complications such as hypertension, hypotension, and diabetes. In terms of blood routine, this group exhibited elevated levels of WBC (white blood cell count), platelets, and absolute neutrophil count (P < 0.05). Furthermore, individuals in this group demonstrated Increased levels of sodium, cholesterol, LDL, and ALT, as well as decreased levels of INR and PT (P < 0.001).
Table 1
Baseline characteristics of the study population by quartiles of the TyG index
| Q1 (N = 268) | Q2(N = 268) | Q3(N = 267) | Q4(N = 268) | p.overall |
TyG, [IQR] | 8.40 [8.17;8.57] | 8.90 [8.79;9.02] | 9.36 [9.24;9.49] | 9.97 [9.78;10.2] | <0.001 |
age, [IQR] | 67.3 [55.9;77.7] | 63.0 [52.2;73.3] | 62.9 [53.9;70.0] | 61.6 [49.5;68.8] | <0.001 |
gender, (%): | | | | | 0.673 |
Female | 109 (40.7%) | 104 (38.8%) | 95 (35.6%) | 101 (37.7%) | |
Male | 159 (59.3%) | 164 (61.2%) | 172 (64.4%) | 167 (62.3%) | |
bmi, [IQR] | 25.2 [21.9;29.3] | 26.0 [23.0;29.9] | 26.9 [23.7;32.5] | 28.3 [24.2;33.6] | <0.001 |
hypotension, (%) | 122 (45.5%) | 145 (54.1%) | 149 (55.8%) | 151 (56.3%) | 0.042 |
hypertension, (%) | 79 (29.5%) | 102 (38.1%) | 78 (29.2%) | 110 (41.0%) | 0.005 |
MI, (%) | 43 (16.0%) | 54 (20.1%) | 52 (19.5%) | 52 (19.4%) | 0.615 |
HF, (%) | 107 (39.9%) | 87 (32.5%) | 91 (34.1%) | 75 (28.0%) | 0.032 |
diabetes, (%) | 60 (22.4%) | 78 (29.1%) | 111 (41.6%) | 137 (51.1%) | <0.001 |
CKD (%) | 84 (31.3%) | 58 (21.6%) | 84 (31.5%) | 70 (26.1%) | 0.030 |
hemoglobin, [IQR] | 9.00 [8.22;10.0] | 9.35 [8.44;10.6] | 9.01 [8.30;9.92] | 8.95 [8.29;10.2] | 0.017 |
platelet, [IQR] | 194 [120;285] | 213 [143;298] | 219 [135;303] | 224 [150;327] | 0.049 |
RDW, [IQR] | 16.4 [14.7;18.2] | 16.1 [14.4;17.6] | 16.2 [14.7;18.1] | 15.9 [14.3;17.8] | 0.068 |
WBC, [IQR] | 9.23 [6.75;12.9] | 10.6 [7.65;13.2] | 10.6 [8.02;13.5] | 11.2 [8.30;14.5] | <0.001 |
neutrophils_abs, [IQR] | 7.61 [4.67;12.2] | 8.98 [5.71;13.1] | 9.32 [5.88;12.9] | 9.52 [5.70;12.5] | 0.037 |
lymphocytes_abs, [IQR] | 0.96 [0.65;1.43] | 1.10 [0.73;1.58] | 1.01 [0.68;1.46] | 1.13 [0.71;1.69] | 0.201 |
monocytes_abs, [IQR] | 0.61 [0.37;0.88] | 0.68 [0.42;0.99] | 0.68 [0.40;0.93] | 0.63 [0.38;0.96] | 0.239 |
albumin, [IQR] | 29.6 [25.6;34.0] | 29.8 [26.6;33.4] | 28.7 [24.7;32.4] | 28.8 [25.2;33.0] | 0.096 |
bicarbonate, [IQR] | 25.1 [23.0;27.0] | 24.8 [22.6;27.0] | 25.0 [22.8;26.5] | 24.3 [22.2;26.5] | 0.141 |
BUN, [IQR] | 8.90 [5.70;14.4] | 10.2 [6.43;15.6] | 11.1 [6.82;16.4] | 10.8 [7.13;16.1] | 0.009 |
calcium, [IQR] | 2.11 [2.02;2.21] | 2.12 [2.04;2.19] | 2.10 [2.01;2.19] | 2.11 [2.00;2.22] | 0.476 |
chloride, Mean (SD) | 103 (5.13) | 102 (4.62) | 101 (4.93) | 103 (4.27) | 0.003 |
creatinine, [IQR] | 95.9 [63.5;200] | 107 [70.7;166] | 111 [71.3;223] | 110 [68.7;202] | 0.195 |
glycemia, [IQR] | 6.50 [5.84;7.65] | 7.09 [6.32;8.32] | 7.96 [6.86;9.52] | 8.91 [7.61;10.5] | <0.001 |
sodium, Mean (SD) | 138 (3.78) | 139 (3.27) | 138 (3.99) | 140 (3.55) | <0.001 |
potassium, [IQR] | 4.13 [3.93;4.35] | 4.11 [3.87;4.34] | 4.11 [3.93;4.35] | 4.13 [3.93;4.38] | 0.529 |
triglyceride, [IQR] | 0.79 [0.64;0.98] | 1.26 [1.09;1.51] | 1.85 [1.56;2.18] | 3.10 [2.44;4.05] | <0.001 |
cholesterol, [IQR] | 2.75 [2.02;3.58] | 3.06 [2.23;3.99] | 3.08 [2.40;4.07] | 3.55 [2.80;4.65] | <0.001 |
HDL, [IQR] | 0.91 [0.62;1.22] | 0.80 [0.53;1.17] | 0.75 [0.52;0.97] | 0.73 [0.47;1.01] | <0.001 |
LDL, [IQR] | 1.37 [0.89;1.94] | 1.68 [1.04;2.29] | 1.58 [1.01;2.25] | 1.63 [1.04;2.49] | 0.001 |
INR, [IQR] | 1.40 [1.22;1.79] | 1.33 [1.15;1.64] | 1.35 [1.21;1.64] | 1.28 [1.16;1.47] | <0.001 |
PT, [IQR] | 15.4 [13.6;19.4] | 14.6 [12.9;17.9] | 14.7 [13.2;18.0] | 14.0 [12.8;16.4] | <0.001 |
ALT, [IQR] | 24.4 [16.1;53.7] | 36.1 [21.0;75.4] | 37.6 [17.5;97.3] | 40.5 [20.0;91.2] | <0.001 |
AST, [IQR] | 37.0 [23.9;64.2] | 43.6 [27.1;91.3] | 40.7 [24.5;96.8] | 44.4 [27.1;105] | 0.014 |
VC_concentration, [IQR] | 16.7 [13.1;20.6] | 16.9 [13.0;20.6] | 17.3 [13.2;20.9] | 16.9 [13.4;20.0] | 0.896 |
VC_duration, [IQR] | 145 [67.8;279] | 140 [78.0;261] | 163 [82.5;300] | 173 [82.0;296] | 0.180 |
VC + PT, (%) | 81 (30.2%) | 107 (39.9%) | 109 (40.8%) | 110 (41.0%) | 0.026 |
VC + VA, (%) | 29 (10.8%) | 38 (14.2%) | 37 (13.9%) | 51 (19.0%) | 0.058 |
VI-AKI, (%) | 132 (49.3%) | 163 (60.8%) | 181 (67.8%) | 198 (73.9%) | <0.001 |
Table 1
Data are presented as mean ± standard deviation (SD) or median (IQR) for continuous variables and proportions (%) for categorical variables.
Abbreviation:MI (Myocardial Infarction), HF (Heart Failure), CKD (Chronic Kidney Disease), RDW (Red Cell Distribution Width), WBC (White Blood Cell Count), BUN (Blood Urea Nitrogen), HDL (high-density lipoprotein), LDL (low-density lipoprotein), INR (International Normalized Ratio), PT (Prothrombin Time), ALT (Alanine Aminotransferase), AST (Aspartate Aminotransferase), VC+PT (Vancomycin and Piperacillin-tazobactam), VC+VA (Vancomycin and Vasoactive agents), VI-AKI (Vancomycin Induced Acute Kidney Injury).
In Figure 1. A, we can observe a clear increase in the proportion of VI-AKI with the rise of the TyG index. Figure 1. B illustrates the SOFA scores across different systems among the groups, the Q4 group exhibited high SOFA scores. Moreover, Figure 1.C depicts a higher proportion of high cardiovascular scores in the Q4 group, while Figure 1.D illustrates a higher proportion of low renal scores in the Q1 group.
3.2. TyG index and endpoints
Cox proportional hazard ratios (HR) for VI-AKI show in Table 2. When the TyG index as a continuous variable, Cox proportional hazards analysis indicated a statistically significant association (P<0.001) between the risk of VI-AKI and the TyG index in all models(Model1: 1.36[95% CI 1.20–1.48]; Model2: 1.32[95% CI 1.20–1.47]; Model3: 1.28[95% CI 1.10–1.49]).
Moreover, when considering the TyG index as a nominal variable, the highest quartile (Q4) of the TyG index exhibited a significant association with the risk of AKI in all models (Q1 vs. Q4 in Model 1: 2.00[95% CI 1.60–2.50]; Model 2: 1.98[95% CI 1.57–2.50]; Model 3: 1.58 [95% CI 1.20–2.00]). Except for the Q1 vs Q2 in Model 3, which was not statistically significant (p=0.1), the Cox proportional hazard ratios for all other were statistically meaningful(p<0.05).
Fig 2 displays the restricted cubic splines regression model, illustrating a linear relationship between the TyG index and VI-AKI risk in models (P for non-linearity in unadjusted model=0.004 and adjusted model=0.224).
Finally, we also conducted Kaplan-Meier analysis for TyG quartile groups with VI-AKI cumulative incidence and the 90-day mortality rate after VI-AKI occurrence (Fig 3). We can observe a clear relationship between the cumulative incidence of VI-AKI and the groups(P<0.001), but there is no association with the 90-day mortality rate.
Table 2. Cox proportional hazard ratios (HR) for VI-AKI
|
Model1
|
|
Model2
|
|
Model3
|
|
HR(95% CI)
|
p-value
|
HR(95% CI)
|
p-value
|
HR(95% CI)
|
`p-value
|
TyG index
|
1.36[95% CI 1.20–1.48]
|
<0.001
|
1.32[95% CI 1.20–1.47]
|
<0.001
|
1.28[95% CI 1.10–1.49]
|
0.001
|
Quartile
|
|
|
|
|
|
|
Q1
|
Ref
|
|
Ref
|
|
Ref
|
|
Q2
|
1.44[95% CI 1.14–1.80]
|
0.002
|
1.43[95% CI 1.13–1.80]
|
0.003
|
1.22[95% CI 0.96–1.56]
|
0.1
|
Q3
|
1.70[95% CI 1.35–2.13]
|
<0.001
|
1.68[95% CI 1.33–2.11]
|
<0.001
|
1.36[95% CI 1.06–1.75]
|
0.01
|
Q4
|
2.00[95% CI 1.60–2.50]
|
<0.001
|
1.98[95% CI 1.57–2.50]
|
<0.001
|
1.58 [95% CI 1.20–2.00]
|
0.001
|
3.2. Subgroup analysis
To further substantiate the relationship between TyG and VI-AKI, we conducted a subgroup analysis,based on gender, age, BMI, Diabetes,CKD, VC+PT, VC+VA. In Figure 4, There is a significant relationship between TyG and VI-AKI for males (HR = 1.30, 95% CI 1.14-1.50), females (HR = 1.37, 95% CI 1.18-1.59), age<65 years (HR = 1.20, 95% CI 1.05-1.37), age ≥65 years (HR = 1.55, 95% CI 1.31-1.83),BMI<30 (HR = 1.38, 95% CI 1.22-1.56), with diabetes (HR = 1.20 95% CI 1.02-1.47), without diabetes (HR = 1.53, 95% CI 1.32-1.77), with CKD (HR = 1.29, 95% CI 1.06-1.56), without CKD (HR = 1.35, 95% CI 1.20-1.52), Vancomycin with Piperacillin-tazobactam (HR = 1.32, 95% CI 1.11-1.57), Vancomycin without Piperacillin-tazobactam (HR = 1.32, 95% CI 1.16-1.50), Vancomycin without vasopressor agents (HR = 1.32, 95% CI 1.18-1.48). However, there is no association between TyG and VI-AKI in patients with BMI ≥ 30 or in patients who used vasopressor agents during vancomycin therapy.