2.1 | Subject characteristics
After reviewing the records of 2435 eligible subjects who were attended to the ICU of the First Affiliated Hospital of the University of South China from 1 January 2016 to 31 December 2019.The final cohort comprised 1500 critically ill patients in the analysis (Fig 1). The subject characteristics of critically ill patients are presented in Table 1. Most patients were men (63.4%); 615 patients (41%) were classified in the AKI group, and 885 patients (59%) were allocated to the non-AKI group. The number of patients with stage 1 AKI was 159 (25.9%), with stage 2 AKI was184 (29.9%) and with stage 3 AKI was 272 (44.2%).
The AKI group with a remarkably higher RDW than non-AKI group. Compared with non -AKI patients, the number of older people was larger and the prevalence rates of hypertension, diabetes mellitus, and coronary artery disease were higher in the AKI patients. The AKI patients had remarkably higher PLRs, cystatin C (CystC), Scr, blood urea nitrogen (BUN),C-reactive protein (CRP), and procalcitonin (PCT) levels and APACHE II scores than the non-AKI group. However, haemoglobin was lower in AKI group. Notably, no statistical differences was observed between the AKI group and non-AKI group in the prevalence of chronic obstructive pulmonary disease (COPD) or albumin level and white blood cells(WBC)(Table1).
Table 1. Subject characteristics
Variables
|
ALL
(n=1500)
|
Patients with AKI (n=615)
|
Patients without AKI
(n=885)
|
p-value
|
Male (%)
|
951(63.4%)
|
404(42.5%)
|
547(57.5%)
|
0.125
|
Age (years)
|
60.1±16.14
|
63.27±16.89
|
58.91±16.73
|
<0.001*
|
Comorbidities
|
|
|
|
|
Hypertension
|
486(32.4%)
|
223(36.3%)
|
263(29.7%)
|
0.008*
|
Diabetes mellitus
|
225(14.9%)
|
127(20.7%)
|
96(10.8%)
|
<0.001*
|
Coronary artery disease
|
263(17.5%)
|
144(23.4%)
|
119(13.4%)
|
<0.001*
|
COPD
|
135(9%)
|
48(7.8%)
|
87(9.8%)
|
0.178
|
Laboratory index at ICU admission
|
|
|
|
|
Baseline Scr (umol/L)
|
100.64±9.8
|
127.34±14.73
|
82.09±19.25
|
<0.001*
|
BUN (mmol/L)
|
10.97±9.25
|
16.58±10.99
|
7.07±4.91
|
<0.001*
|
Albumin (g/l)
|
33.45±6.91
|
32.16±4.79
|
34.35±6.85
|
0.364
|
Triglycerides (mmol/l)
|
1.15(0.79,1.72)
|
1.23(0.87,1.24)
|
1.09(0.75,1.66)
|
0.002*
|
PCT (ng/ml)
|
0.52(0.17,3.88)
|
1.86(0.31,16)
|
0.26(0.14,1.4)
|
<0.001*
|
WBC count/mm3
|
11.77(8.26,17.0)
|
12.23(8.46,12.23)
|
11.59(8.11,16.28)
|
0.786
|
Haemoglobin (g/dl)
|
104.98±29.75
|
103.06±20.81
|
106.31±29.65
|
0.038*
|
CystC
|
1.38(0.89,2.72)
|
2.75(1.86,4.6)
|
1.01(0.75,1.41)
|
<0.001*
|
CRP
|
37.22(8.28,95.24)
|
55.78(17.02,131.59)
|
25.47(4.6,76.08)
|
<0.001*
|
APACHE II score
|
16.50±7.32
|
19.09±7.42
|
16.69±6.7
|
<0.001*
|
RDW
PLR
|
14.65±2.14
188.16±129.2
|
15.72±2.30
277.3±133.5
|
13.91±1.37
153.1±111.3
|
<0.001*
<0.001*
|
AKI, acute kidney injury; COPD, chronic obstructive pulmonary disease; Scr, serum creatinine; BUN, blood urea nitrogen; PCT, procalcitonin; WBC,white Blood Cell; CystC, cystatin C; CRP, C-reactive protein; APACHE II, Acute Physiology and Chronic Health Evaluation II;RDW, red cell distribution width, PLR, platelet-to- lymphocyte ratio.
2.2 The association of RDW with other parameters
RDW and PLR were positively associated with CRP, PCT, ferritin and CystC levels (P<0.05) and negatively associated with albumin and haemoglobin levels. There was no correlation between RDW and WBC count. The PLR was positively associated with RDW and PCT, CRP and CystC levels (P<0.05), and no correlation was observed between PLR and albumin, haemoglobin or triglyceride level or WBC count (Table 2).
Table2.Bivariate correlation analyses of baseline RDW/PLR and laboratory indicators
Variable
|
RDW (r)
|
P value
|
PLR (r)
|
P value
|
RDW (%)
|
1
|
-
|
0.182
|
0.000
|
PCT
|
0.161
|
0.000
|
0.122
|
0.000
|
CRP
|
0.108
|
0.001
|
0.102
|
0.000
|
WBC count
|
-0.04
|
0.09
|
0.000
|
0.999
|
PLR
|
0.182
|
0.000
|
1
|
-
|
Haemoglobin (g/l)
|
-0.297
|
0.000
|
-0.021
|
0.406
|
Albumin (g/l)
|
-0.229
|
0.000
|
-0.044
|
0.086
|
Triglycerides (mmol/l)
|
0.081
|
0.004
|
0
|
0.983
|
CystC
|
0.370
|
0.000
|
0.317
|
0.000
|
RDW, red blood cell distribution width; PLR, platelet-to-lymphocyte ratio; PCT, procalcitonin; CRP, C-reactive protein; WBC, white blood cell; CystC, cystatin C.
2.3 RDW /PLR and the development of AKI
After multi-variable adjustment, the risk of the occurrence of AKI in critically ill patients with an elevated RDW and PLR was 1.381 (95% CI:1.300-1.467) and 1.008 (95% CI: 1.007-1.009), respectively. We further divided the patients into four subgroups: RDW-low (RDW<14.045), RDW-high (≥14.045), PLR-low (PLR <172.067) and PLR-high (PLR (≥172.067). Patients within the RDW-high group had a 5.189-fold higher risk of developing AKI than those in the RDW-low group (OR=5.189, 95% CI: 4.088-6.588) (Table 3), and those in the PLR-high group had a 9.109-fold higher risk of developing AKI t (OR= 9.109, 95% CI:7.089-11.705)han those in the PLR-low group. Moreover, CystC, CRP, PCT and triglyceride levels and the APACHE II score were identified as potential risk factors for the development of AKI.
Table 3. Univariate and multivariate logical regression analysis for the prevalence of AKI
Variable
|
Unadjusted
|
|
Adjusted
|
|
|
OR (95%CI)
|
P value
|
OR (95%CI)
|
P value
|
RDW (%)
|
1.381(1.30-1.47)
|
0.000
|
1.28(1.19-1.36)
|
0.000
|
RDW-low (<14.045%)
|
1 (reference)
|
|
1 (reference)
|
|
RDW-high (≥14.045%)
|
5.23(4.17-6.56)
|
0000
|
5.19(4.09-6.59)
|
0.000
|
PCT
|
1.03(1.02-1.04)
|
0.000
|
1.03(1.02-1.13)
|
0.000
|
CRP
|
1.01(1.00-1.02)
|
0.000
|
1.01(1.00-1.02)
|
0.000
|
WBC count
|
1.00(0.99-1.01)
|
0.705
|
1.00(0.99,1.01)
|
0.383
|
CystC
|
2.95(2.58-3.37)
|
0.000
|
2.86(2.50-3.27)
|
0.000
|
Albumin (g/l)
|
0.95(0.94-0.97)
|
0.000
|
0.98(0.97-1.00)
|
0.101
|
Haemoglobin
|
1.00(0.98-1.00)
|
0.038
|
1.00(0.99,1.01)
|
0.494
|
PLR
|
1.01(1.00-1.02)
|
0.000
|
1.01(1.00-1.02)
|
0.000
|
PLR-low (<172.067)
|
1 (reference)
|
0.000
|
1 (reference)
|
0.000
|
PLR-high (≥172.067)
|
9.30(7.31-11.82)
|
0.000
|
9.11(7.09-11.71)
|
0.000
|
Triglycerides (mmol/l)
|
1.09(1.03-1.16)
|
0.000
|
1.10(1.03-1.17)
|
0.004
|
APACHE II score
|
1.09(1.075,1.109)
|
0.000
|
1.07(1.05-1.09)
|
0.000
|
Adjusted by sex, age, hypertension,diabetes mellitus, coronary artery disease, COPD, baseline Scr and BUN. AKI, acute kidney injury; BUN, blood urea nitrogen; PCT, procalcitonin; CystC, cystatin C; CRP, C-reactive protein; RDW, red blood cell distribution width; APACHE II, Acute Physiology and Chronic Health Evaluation II; PLR, platelet-to-lymphocyte ratio.
2.4 RDW and PLR predicted the occurrence of AKI
The ROC curve was used to assess the discriminative ability of RDW in predicting AKI in ICU compared with other inflammation index parameters (including the PLR, CRP, PCT and CystC). The AUC for AKI development based on RDW was 0.728 (95% CI:0.702-0.754), and the optimal cut-off value was 14.045; with the sensitivity was 73.3%, and the specificity was 65.5%, which were higher than those for PCT, CRP and the APACHE II score (Fig 2a, Table 4). The AUC for AKI development based on the PLR was 0.780 (95% CI: 0.755-0.804), with a cut-off value of 172.067 (sensitivity: 77.1%, specificity: 73.4%). However, CystC was associated with the highest AUC, at 0.821 (95% CI: 0.800-0.843) (Fig 2b, Table 4).
2.5 Risk of in-hospital mortality predicted by multi-variable logical regression
After adjustment for male, age, diabetes mellitus, hypertension, COPD, coronary artery disease, baseline Scr and BUN, the adjusted ORs for in-hospital mortality based on RDW was 1.202 (1.136-1.271); there was no relationship between the PLR and in-hospital mortality. Therefore, we divided the patients into two subgroups for each parameter: RDW-low and RDW-high and PLR-low and PLR-high. The adjusted ORs for in-hospital mortality in the RDW-high group were 2.907 and 1.534, respectively. The adjusted ORs for in-hospital mortality based on WBC count, CystC, and the APACHE II score were 1.016, 1.128 and 1.095, respectively (P<0.05). However, albumin, haemoglobin and triglycerides unrelated to mortality(P>0.05). (Table5)
Table 5 The predictive indicators of in-hospital mortality
Variable
|
Unadjusted
|
|
Adjusted
|
|
|
OR (95%CI)
|
P
|
OR (95%CI)
|
P
|
RDW (%)
|
1.224(1.160-1.292)
|
0.000
|
1.202(1.136-1.271)
|
0.000
|
RDW-low (<14.045%)
|
1 (reference)
|
0.000
|
1 (reference)
|
0.000
|
RDW-high (≥14.045%)
|
3.023(2.888-3.994)
|
0.000
|
2.907(2.190-3.858)
|
0.000
|
PLR
|
1.001(1.000-1.002
|
0.056
|
1.000(0.999-1.001)
|
0.529
|
PLR-low (<170.067)
|
1 (reference)
|
0.000
|
1 (reference)
|
0.000
|
PLR-high (≥170.067)
|
1.629(1.258-2.109)
|
0.000
|
1.534(1.179-1.995)
|
0.000
|
WBC count
|
1.014(1.000-1.029)
|
0.051
|
1.016(1.002-1.031)
|
0.026
|
CystC
|
1.183(1.111-1.260)
|
0.000
|
1.128(1.047-1.214)
|
0.001
|
Albumin (g/L)
|
0.983(0.965-1.002)
|
0.076
|
0.992(0.972-1.012)
|
0.417
|
Haemoglobin
|
0.997(0.993-1.001)
|
0.166
|
0.998(0.994-1.003)
|
0.447
|
Triglycerides (mmol/L)
|
1.014(0.961-1.069)
|
0.614
|
1.023(0.967-1.082)
|
0.426
|
APACHE II score
|
1.103(1.083-1.123)
|
0.000
|
1.095 (1.074-1.116)
|
0.000
|
Baseline Scr (umol/L)
|
1.005(1.002-1.007)
|
0.001
|
|
|
BUN (mmol/L)
|
1.029(1.016-1.042)
|
0.000
|
|
|
Adjusted for male, age, hypertension, diabetes mellitus, coronary artery disease, COPD, baseline Scr, and BUN. AKI, acute kidney injury; PCT, procalcitonin; CystC, cystatin C; CRP, C-reactive protein; APACHEII, Acute Physiology and Chronic Health Evaluation II; RDW, red cell distribution width;PLR, platelet-to- lymphocyte ratio.
The prognostic cut-off value for RDW identified by the ROC curve followed by Youden’s test was 14.45 (AUC 0.663; 95% CI, 0.628‒0.698). The AUC for AKI based on CystC was 0.614 (95% CI:0.575-0.653), with a sensitivity of 61.6% and a specificity of 57.6%. The APACHE II score was associated with the highest AUC: 0.706 (95% CI:0.673-0.738). PLR, CRP and PCT did not show a clear ability to predict in-hospital mortality considering a cut-off value of 0.5 (Table 6).