The MIMIC III database contains records for 61567 admissions, of which 15091 were excluded for duplications. Of the remaining 46476 admissions, 7938 were excluded because of age less than 18 years old, and 3921 were excluded because of data shortage. Finally, 34617 patients were included in this analysis. Among them, 7364 admissions were AKI patients and 27253 admissions were non-AKI patients. The flow diagram of patient selections was presented in Fig. 1.
Demographic characteristics of the AKI and non-AKI were presented in Table 1. The number of patients of each disease subgroup was as follows: cerebral group (8883, 25.7%), cardiac group (28887, 83.4%), respiratory group (16833, 55.0%) and gastrointestinal group (13424, 38.8%). Group of AKI owed more complication of chronic kidney disease (CKD) or sepsis or septic shock but less history of diabetes, hypertension, heart failure, and chronic obstructive pulmonary disease. AKI patients presented higher level of glomerular filtration rate (eGFR), creatinineinitial, and creatininemax than non-AKI patients, and more patients in the AKI group underwent RRT. For the level of chloride, higher level of chloride_max and Δchloride but not chloride_initial was shown in the group of AKI patients.
Table 1
Comparisons of demographics between AKI and non-AKI
Variable | AKI | Non-AKI | P value |
N Male sex | 7364 4236 | 27253 15528 | 0.401 |
Age (year) | 84.8 ± 64.9 | 71.8 ± 50.7 | < 0.000 |
Cerebral disease (N) | 2116 | 6767 | < 0.000 |
Cardiac disease (N) | 6529 | 22358 | < 0.000 |
Respiratory disease (N) | 4826 | 12007 | < 0.000 |
Gastrointestinal disease (N) | 3929 | 9495 | < 0.000 |
History of | | | |
CKD (N) | 1576 | 1158 | < 0.000 |
DM (N) | 2548 | 6483 | < 0.000 |
Hypertension (N) | 2619 | 12671 | < 0.000 |
Heart failure (N) | 2993 | 5501 | < 0.000 |
COPD (N) | 231 | 468 | < 0.000 |
Sepsis or septic shock (N) | 1951 | 1387 | < 0.000 |
eGFR (ml/min/1.73 m2) | 37.4 ± 49.6 | 85.5 ± 70.3 | < 0.000 |
Creatinineinitial (mg/L) | 2.1 ± 1.8 | 1.1 ± 1.1 | < 0.000 |
Creatininemax (mg/L) | 2.4 ± 2.0 | 1.2 ± 1.2 | < 0.000 |
RRT (N) | 538 | 100 | < 0.000 |
Chlorideinitial (mmol/L) | 105.4 ± 7.4 | 105.9 ± 5.7 | 0.005 |
Chloridemax (mmol/L) | 110.6 ± 6.8 | 108.6 ± 5.2 | < 0.000 |
ΔChloride (mmol/L) | 11.1 ± 6.9 | 8.2 ± 5.7 | < 0.000 |
AKI: acute Kidney Injury; CKD: chronic kidney disease; DM: diabetes; COPD: chronic obstructive pulmonary disease; SOFA: sequential organ failure assessment score; SAPS: simplified acute physiology score; RRT: renal replacement therapy; eGFR: glomerular filtration rate. The standard deviation (SD) was shown in brackets. |
Clinical outcome was explored between the hyperchloremia and non-hyperchlomeria patients. Crude outcomes were observed in Table 2 for patients with hyperchloremia and non-hyperchlomeria. Without adjusting for other factors, higher incidence rate of AKI and RRT were observed in the hyperchloremia group. Hyperchloremia patients presented increased mortality during ICU, as well as higher hospital mortality rate compared to the non-hyperchlomeria group. Besides, the hyperchloremia group was associated with longer LOS and ICU length. In addition, patients with hyperchloremia owed higher score of SOFA and SAPS II than the non-hyperchlomeria group.
Table 2
Unadjusted outcomes by max serum chloride categories in all patients
Outcomes | Total (n = 34617) | Hyperchloremia (n = 12667) | Non-hyperchloremia (n = 21950) | p |
AKI (n(%)) | 7364(21.8) | 3656(28.9) | 3691(16.8) | < 0.000 |
RRT (n(%)) | 638(1.8) | 306(2.4) | 332(1.5) | < 0.000 |
Hospital mortality [n(%)] | 3952(11.4) | 1980(15.6) | 1972(9.0) | < 0.000 |
ICU mortality [n(%)] | 2971(8.4) | 1463(11.5) | 1508(6.9) | < 0.000 |
Hospital LOS (days) [median(IQR)] | 7.0(4.2–12.1) | 8.8(5.2–16.2) | 6.3(3.8–10.3) | < 0.000 |
ICU LOS (days) [median(IQR)] | 2.2(1.3–4.4) | 3.1(1.7–7.1) | 2.0(1.1–3.5) | < 0.000 |
SOFA [median(IQR)] | 4(2–6) | 4(3–7) | 3(1–5) | < 0.000 |
SAPS II [median(IQR)] | 33(25–43) | 37(29–47) | 31(23–40) | < 0.000 |
ICU: intensive care unit; LOS: length of stay; AKI: acute Kidney Injury; RRT: renal replacement therapy; SOFA: SOFA, sequential organ failure assessment; SAPS II: Simplified Acute Physiology Score. |
Relationship between level of chloride and AKI incidence was analyzed using the univariate and multivariate logistic regression (Table 3). As insignificant chloride_initial was noticed in terms of AKI, chloride_max was categorized into six groups, which were used as design variables in six regression models. The normal level of serum chloride (95–110 mmol/L) was served as the reference group. Results showed that both hypochlorimia ((chloride_max < 95) and hyperchlorimia (chloride_max > 110) were significantly associated with increased AKI. As the higher level of hyperchlorimia, the bigger adjusted odds ratio (OR) presented in terms of AKI, with the OR increasing from 1.13 (95%CI 1.06–1.21) to 4.09 (95%CI 3.04–5.52). Besides, the multivariate logistic regression analyses showed a significant positive effect of diabetes, chronic kidney disease, heart failure, COPD, and sepsis in terms of AKI.
Table 3
Cox proportional hazard models exploring the association of chloride_max with AKI
Variable | Univariate model | Multivariate model |
Odds ratio | 95%CI | P | Odds ratio | 95%CI | P |
Chloride_max (< 95) | 2.88 | 1.98–2.84 | < 0.000 | 1.84 | 1.51–2.24 | < 0.000 |
Chloride_max (95–109) | Ref. | - | - | Ref. | - | - |
Chloride_max (110–114) | 1.15 | 1.08–1.21 | < 0.000 | 1.13 | 1.06–1.21 | < 0.000 |
Chloride_max (115–119) | 2.04 | 1.85–2.26 | < 0.000 | 1.78 | 1.60-2.00 | < 0.000 |
Chloride_max (120–124) | 3.02 | 2.46–3.71 | < 0.000 | 2.67 | 2.12–3.36 | < 0.000 |
Chloride_max (≥ 125) | 4.43 | 3.40–5.78 | < 0.000 | 4.09 | 3.04–5.52 | < 0.000 |
Age | 1.00 | 1.00–1.00 | < 0.000 | 1.00 | 1.00–1.00 | < 0.000 |
DM | 1.70 | 1.61–1.80 | < 0.000 | 1.36 | 1.28–1.45 | < 0.000 |
CKD | 6.13 | 5.65–6.65 | < 0.000 | 4.60 | 4.20–5.05 | < 0.000 |
Heart failure | 2.71 | 2.56–2.86 | < 0.000 | 2.17 | 2.03–2.31 | < 0.000 |
Hypertension | 0.64 | 0.60–0.67 | < 0.000 | 0.83 | 0.78–0.88 | < 0.000 |
COPD | 6.13 | 5.65–6.65 | < 0.000 | 1.57 | 1.32–1.88 | < 0.000 |
Sepsis | 6.72 | 6.23–7.24 | < 0.000 | 6.52 | 6.03–7.06 | < 0.000 |
AKI: acute Kidney Injury; DM: diabetes; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease |
The specific relationship between chloride_max and incidence rate of AKI for patients in terms of cerebral, cardiac, respiratory and gastrointestinal disease subgroups was analyzed using the Lowess Smoothing technique (Fig. 2). We observed that the normal level of chloride (95–110 mmol/L) was associated with the lower incidence of AKI rate compared to the hypochloremia (< 95 mmol/L) or the hyperchloremia (> 110 mmol/L) in patients with any of the four systematic diseases. Observed lowest AKI rate was shown in the chloride level of 105–110 mmol/L. Thus, it suggests that chloride level of 105–110 mmol/L might be the optimal chlorimia in cerebral, cardiac, respiratory or gastrointestinal patients. Meanwhile, another four logistic regression models were built for analysis of the cerebral, cardiac, respiratory and gastrointestinal disease subgroups. Figure 2 shows the OR and 95%CI for the four subgroups. A similar trend showed that OR was increased either in group of hyperchloremia or the group of hypochlormia, which indicated the normal chlormia contributed to less AKI in ICU.
Receiver operating characteristic curves were applied to analyze the diagnostic value of hyperchloremia (chloride_max > 110 mmol/L) in these four subgroup patients (Fig. 3). The results showed the diagnostic performance was good for cerebral disease (AUC = 0.617), cardiac disease (AUC = 0.636), respiratory disease (AUC = 0.623) and gastrointestinal disease (AUC = 0.633). The optimal cut-off value in terms of chloride_max for diagnosing AKI was 116 for the subgroup of cerebral, respiratory and gastrointestinal diseases. It indicated that hyperchloremia (chloride_max > 116 mmol/L) could be used to predictive diagnostic of AKI in ICU patients with cerebral, respiratory, or gastrointestinal diseases. For the subgroup of cardiac patients, the cut-off value was shown in 115, which suggested that hyperchloremia (chloride_max > 115 mmol/L) could be applied to predictive diagnostic of AKI in ICU.