3.1 Participants and baseline characteristics. A total of 961 patients with AP were reviewed according to the ICD-9 code.We excluded 468 participants who did not meet the inclusion criteria. A total of 493 participants of AP were included in the study. Figure 1 describes the inclusion and exclusion processes of the study population. The demographic and clinical characteristics of participants by levels of eGFR are summarized in Table 1. Of the 493 included participants, 231 were female (46.86%) and 262 (53.14%) were male. The mean age of participants was 60.15±17.49 years. Age, BUN, creatinine, SOFA score, in-hospital mortality, in-ICU mortality, and ICU 28-day mortality were significantly higher in patients with eGFR <30 ml/min/1.73 m2 than in those with eGFR ≥90 ml/min/1.73 m2.
Table 1. Baseline characteristics of participants by levels of estimated glomerular filtration rate (eGFR).
Characteristics
|
|
Levels of eGFR (ml/min/1.73 m2)
|
|
Overall
|
<30
|
30-60
|
60-90
|
≥90
|
P-value
|
|
N=493
|
N=118
|
N=111
|
N=106
|
N=158
|
|
Demographics
|
|
|
|
|
|
|
Age
|
60.15 (17.49)
|
67.80 ± 18.31
|
68.10 ± 13.58
|
62.06 ± 15.71
|
47.58 ± 12.85
|
<0.001
|
Sex
|
|
|
|
|
|
0.112
|
Female
|
231 (46.86%)
|
64 (54.24%)
|
45 (40.54%)
|
54 (50.94%)
|
68 (43.04%)
|
|
Male
|
262 (53.14%)
|
54 (45.76%)
|
66 (59.46%)
|
52 (49.06%)
|
90 (56.96%)
|
|
Clinical features, N (%)
|
|
|
|
|
|
Congestive heart failure
|
|
|
|
|
<0.001
|
No
|
391 (79.31%)
|
86 (72.88%)
|
79 (71.17%)
|
85 (80.19%)
|
141 (89.24%)
|
|
Yes
|
102 (20.69%)
|
32 (27.12%)
|
32 (28.83%)
|
21 (19.81%)
|
17 (10.76%)
|
|
Cardiac arrhythmias
|
|
|
|
|
<0.001
|
No
|
342 (69.37%)
|
72 (61.02%)
|
69 (62.16%)
|
70 (66.04%)
|
131 (82.91%)
|
|
Yes
|
151 (30.63%)
|
46 (38.98%)
|
42 (37.84%)
|
36 (33.96%)
|
27 (17.09%)
|
|
Hypertension
|
|
|
|
|
|
<0.001
|
No
|
218 (44.22%)
|
37 (31.36%)
|
45 (40.54%)
|
44 (41.51%)
|
92 (58.23%)
|
|
Yes
|
275 (55.78%)
|
81 (68.64%)
|
66 (59.46%)
|
62 (58.49%)
|
66 (41.77%)
|
|
Chronic pulmonary disease
|
|
|
|
|
0.26
|
No
|
420 (85.19%)
|
102 (86.44%)
|
88 (79.28%)
|
92 (86.79%)
|
138 (87.34%)
|
|
Yes
|
73 (14.81%)
|
16 (13.56%)
|
23 (20.72%)
|
14 (13.21%)
|
20 (12.66%)
|
|
Diabetes
|
|
|
|
|
|
0.05
|
No
|
352 (71.40%)
|
76 (64.41%)
|
78 (70.27%)
|
73 (68.87%)
|
125 (79.11%)
|
|
Yes
|
141 (28.60%)
|
42 (35.59%)
|
33 (29.73%)
|
33 (31.13%)
|
33 (20.89%)
|
|
Alcohol consumption
|
|
|
|
|
0.739
|
No
|
361 (73.23%)
|
90 (76.27%)
|
83 (74.77%)
|
75 (70.75%)
|
113 (71.52%)
|
|
Yes
|
132 (26.77%)
|
28 (23.73%)
|
28 (25.23%)
|
31 (29.25%)
|
45 (28.48%)
|
|
Blood biochemistry, mean (SD)
|
|
|
|
|
|
eGFR ml/min/1.73 m2
|
65.93 (38.56)
|
16.07 ± 7.17
|
46.48 ± 8.64
|
73.97 ± 9.50
|
111.44 ± 15.68
|
<0.001
|
Creatinine, mg/dl
|
1.10 (0.20-16.20)
|
3.42 ± 2.12
|
1.45 ± 0.33
|
0.98 ± 0.20
|
0.68 ± 0.17
|
<0.001
|
BUN, mmol /L
|
28.37 (22.21)
|
53.19 ± 27.56
|
31.54 ± 14.12
|
20.19 ± 8.25
|
13.09 ± 6.66
|
<0.001
|
WBC, 10^9/L
|
15.67 (7.72)
|
15.83 ± 8.14
|
16.58 ± 8.45
|
16.04 ± 7.05
|
14.66 ± 7.24
|
0.211
|
SOFA score, mean (SD)
|
4.83 (3.56)
|
7.86 ± 3.99
|
4.92 ± 2.78
|
4.00 ± 2.81
|
3.05 ± 2.59
|
<0.001
|
SIRS score, mean (SD)
|
3.09 (0.86)
|
3.04 (0.97)
|
3.10 (0.86)
|
3.16 (0.81)
|
3.08 (0.82)
|
0.783
|
RRT, N (%)
|
|
|
|
|
|
<0.001
|
No
|
474 (96.15%)
|
103 (87.29%)
|
110 (99.10%)
|
103 (97.17%)
|
158 (100.00%)
|
|
Yes
|
19 (3.85%)
|
15 (12.71%)
|
1 (0.90%)
|
3 (2.83%)
|
0 (0.00%)
|
|
ICU 28-day mortality, N (%)
|
|
|
|
|
<0.001
|
No
|
434 (88.03%)
|
87 (73.73%)
|
98 (88.29%)
|
98 (92.45%)
|
151 (95.57%)
|
|
Yes
|
59 (11.97%)
|
31 (26.27%)
|
13 (11.71%)
|
8 (7.55%)
|
7 (4.43%)
|
|
In-hospital mortality, N (%)
|
|
|
|
|
<0.001
|
No
|
428 (86.82%)
|
83 (70.34%)
|
98 (88.29%)
|
97 (91.51%)
|
150 (94.94%)
|
|
Yes
|
65 (13.18%)
|
35 (29.66%)
|
13 (11.71%)
|
9 (8.49%)
|
8 (5.06%)
|
|
In-ICU mortality, N (%)
|
|
|
|
|
<0.001
|
No
|
445 (90.26%)
|
90 (76.27%)
|
103 (92.79%)
|
100 (94.34%)
|
152 (96.20%)
|
|
Yes
|
48 (9.74%)
|
28 (23.73%)
|
8 (7.21%)
|
6 (5.66%)
|
6 (3.80%)
|
|
Abbreviation: eGFR, estimated glomerular filtration rate; SD, standard deviation; RRT, renal replacement therapy; BUN, blood urea nitrogen; WBC, white blood cell; SOFA score, Sequential Organ Failure Assessment score; SIRS, score, systemic inflammatory response syndrome; ICU, intensive care unit.
3.2 Association between eGFR and all-cause mortality. Table 2 shows that 28-day mortality was negatively correlated with eGFR in the crude model (non-adjusted model) and full adjusted models. The hazard ratio (HR) and 95% confidence interval (CI) was 0.80 (0.73, 0.86) in the crude model when eGFR increased by 10 ml/min/1.73 m2. In model I, which was adjusted for age and sex, the HR (95% CI) was 0.82 (0.75, 0.90). In model II, after adjusting for age, sex, hypertension, diabetes mellitus, congestive heart failure, chronic pulmonary disease, alcohol consumption, cardiac arrhythmias, BUN, WBC, and the SIRS score, the HR (95% CI) was 0.85 (0.76, 0.96).
For the purpose of sensitivity analysis, we converted eGFR into a categorical variable using clinical cut-off points using multivariate proportional hazards regression models and calculated P for trend. The higher eGFR (≥90 ml/min/1.73 m2) group was used as the reference group, and the risk of 28-day all-cause mortality significantly increased in the lower eGFR (<30 ml/min/1.73 m2) group after adjusting for potential covariates. The adjusted HR (95% CI) was 4.96 (1.41, 17.36) (P = 0.012). The P value for the trend was 0.010.
Table 2. Relationship between eGFR and 28-day mortality in different Cox proportional hazards regression models
Exposure
|
Crude Model
|
|
Model I
|
|
Model II
|
|
HR (95%CI)
|
P-value
|
|
HR (95%CI)
|
P-value
|
|
HR (95%CI)
|
P-value
|
eGFR per increase 10 ml/min/1.73m2
|
0.80 (0.73, 0.86)
|
<0.0001
|
|
0.82 (0.75, 0.90)
|
<0.0001
|
|
0.85 (0.76, 0.96)
|
0.008
|
eGFR groups
|
|
|
≥90
|
Ref
|
|
|
Ref
|
|
|
Ref
|
|
60-90
|
2.58 (0.79, 8.37)
|
0.115
|
|
1.78 (0.54, 5.87)
|
0.345
|
|
2.16 (0.64, 7.23)
|
0.214
|
30-60
|
4.70 (1.60, 13.81)
|
0.005
|
|
2.66 (0.86, 8.21)
|
0.088
|
|
2.60 (0.82, 8.21)
|
0.104
|
<30
|
9.13 (3.19, 26.10)
|
<0.0001
|
|
5.82 (1.96, 17.26)
|
0.002
|
|
4.96 (1.41, 17.36)
|
0.012
|
P for trend
|
|
<0.0001
|
|
|
<0.0001
|
|
|
0.010
|
|
|
|
|
|
|
|
|
|
|
|
|
Crude Model: Adjusted none.
Model I: Adjusted for gender; age;
Model II: Adjusted for age, gender, hypertension, diabetes mellitus, congestive heart failure, chronic pulmonary disease, alcohol consumption, cardiac arrhythmias, BUN, WBC, and the SIRS score.
Abbreviation: eGFR, estimated glomerular filtration rate; HR, hazard ratio; Ref, reference; CI, Confidence interval; BUN, blood urea nitrogen; WBC, white blood cell; SIRS score, systemic inflammatory response syndrome.
3.3 Non-linear association between eGFR and all-cause mortality. Figure 2 shows the non-linear association between eGFR and 28-day mortality (A), eGFR and in-hospital mortality (B), and eGFR and in-ICU mortality (C) by a Cox proportional hazard regression model with restricted cubic spline and smooth curve fitting. We adjusted for age, sex, hypertension, diabetes mellitus, congestive heart failure, chronic pulmonary disease, alcohol consumption, cardiac arrhythmias, BUN, WBC, and SIRS score. We further calculated the threshold inflection point as 57 ml/min/1.73 m2 using a two-piecewise regression model in Table 3. There was a negative correlation between eGFR and 28-day all-cause mortality on the left of the threshold inflection point, the HR (95% CI) was 0.97 (0.95, 0.99), p < 0.0034. However, there was no significant association on the right of the inflection point (HR 1.00; 95% CI 0.98-1.02; p = 0.8003).
Table 3. Threshold effect analysis of the relationship between eGFR and 28-day mortality using a two-piecewise regression model
eGFR inflection point
|
OR (95% CIs)
|
p-value
|
< 57 ml/min/1.73m2
|
0.97 (0.95, 0.99)
|
0.0034
|
≥ 57 ml/min/1.73m2
|
1.00 (0.98, 1.02)
|
0.8003
|
P for log likelihood ratio test
|
|
0.049
|
Adjusted for age, gender, hypertension, diabetes mellitus, congestive heart failure, chronic pulmonary disease, alcohol consumption, cardiac arrhythmias, BUN, WBC, and the SIRS score.
Abbreviation: eGFR, estimated glomerular filtration rate; OR, odds ratio; Ref, reference; CI, Confidence interval; BUN, blood urea nitrogen; WBC, white blood cell; SIRS score, systemic inflammatory response syndrome.
3.4 eGFR and 28-day all cause mortality. Figure 3 shows the Kaplan–Meier survival curve for 28-day all-cause mortality stratified by the clinical cut-off point of eGFR levels (A) and by the inflection point of eGFR (B). The curves of lower eGFR groups (<30 ml/min/1.73 m2 and <57 ml/min/1.73 m2) separated early and continued to diverge throughout the 28-day follow-up. The risk of 28-day mortality in the groups with eGFR <30 ml/min/1.73 m2 and <57 ml/min/1.73 m2 was significantly higher than in the other groups (log-rank test P value < 0.0001).
We further determined that in-hospital and in-ICU mortality were both negatively correlated with eGFR using Cox proportional hazards regression models (Table 4). When eGFR increased by 10 ml/min/1.73 m2, the HR (95% CI) of in-hospital mortality was 0.87 (0.77, 0.98) (P=0.026) and the HR (95% CI) of in-ICU mortality was 0.87 (0.76, 1.01) (P=0.068) after adjusting for age, sex, hypertension, diabetes mellitus, congestive heart failure, chronic pulmonary disease, alcohol consumption, cardiac arrhythmias, BUN, WBC, and SIRS scores.
Table 4. Cox proportional hazards regression models according to eGFR (per increase 10 ml/min/1.73m2).
Variable
|
Crude Model
|
|
Adjusted Model
|
|
HR (95% CI)
|
p-value
|
|
HR (95% CI)
|
p-value
|
In-hospital mortality
|
0.82 (0.76,0.89)
|
<0.0001
|
|
0.87 (0.77,0.98)
|
0.026
|
In-ICU mortality
|
0.84 (0.77,0.93)
|
<0.0001
|
|
0.87 (0.76,1.01)
|
0.068
|
Crude Model: Adjusted none.
Adjusted model: Adjusted for age, gender, hypertension, diabetes mellitus, congestive heart failure, chronic pulmonary disease, alcohol consumption, cardiac arrhythmias, BUN, WBC, and the SIRS score.
Abbreviation: eGFR, estimated glomerular filtration rate; HR: hazard ratio; Confidence interval; BUN, blood urea nitrogen; WBC, white blood cell.
The subgroup analysis (Fig. 4) further verified the robustness of the results. As shown in Figure 4, the 28-day all cause mortality was negatively correlated with eGFR in different characteristics.The change in the population with hypertension was more obvious (P for interaction = 0.001, HR: 0.7 with hypertension vs. 0.89 with no-hypertension).