The association between the duration of postoperative acute kidney injury and in-hospital mortality in critically ill patients after non-cardiac surgery: an observational cohort study

Figures & data

Figure 1. Data flow diagram.

Table 1. Definition and stage for AKI, according to the KDIGO classification.

Stage	SCr criterion	UO criteria
Stage 1	≥0.3 mg/dL increase within 48 h or 1.5–1.9 times baseline	<0.5 mL/kg/h for 6–12 h
Stage 2	2.0–2.9 times baseline	<0.5 mL/kg/h for ≥12 h
Stage 3	≥3.0 times baseline or increase in serum creatinine to ≥4.0 mg/dL, or initiation of renal replacement therapy	<0.3 mL/kg/h × 24 h or <0.3 mL/kg/h for ≥24 h or anuria for ≥12 h

Notes: SCr, serum creatinine; UO, urine output.

Table 2. Patients’ demographic data and clinical characteristics.

Parameters	All patients N = 318	Non-AKI N = 220	1st tertile N = 34	2nd tertile N = 30	3rd tertile N = 34	p-Value
Age (years)	65.6 ± 14.9	66.1 ± .5	65.2 ± 13.2	61.0 ± 15.1	63.8 ± 17.7	0.255
Male (%)	225 (71)	155 (70)	28 (82)	20 (67)	22 (65)	0.382
BMI (kg/m^2)	23.6 ± 4.8	23.8 ± 4.2	22.5 ± 4.2	23.3 ± 3.8	23.9 ± 4.2	0.373
Cigarette smoker (%)	38 (11.9)	25 (11.3)	4 (11.7)	5 (16.7)	4 (11.7)	0.666
Ventilator dependency (%)	246 (77)	168 (76)	24 (71)	25 (83)	29 (85)	0.461
Emergent surgery (%)	171 (54)	117 (53)	17 (50)	17 (57)	20 (59)	0.470
ICU stay (days)*	6 (3–14)	4 (3–8)	5 (3–13)	6 (3–13)	10 (5–18)	0.001**
8Length of hospitalization (days)^+	31 (13–39)	29 (14–43)	22 (11–38)	27 (14–39)	42 (16–54)	<0.001***
Mean arterial pressure (mm Hg)^+	91.3 (74.0–110)	92.5 (76.3–104.4)	85 (70–100.4)	95 (72–102)	86 (63–107)	0.107
Duration of AKI (days)^+	2 (0–5)	0	1.5 (1–2)	4 (3–7)	10 (7–17)	<0.001***
The least urine output (mL/day)	1855 (920–2280)	1935 (1180–2490)	1561 (580–1775)	1802 (910–2310)	1694 (980–1973)	0.447
Underlying disease
Diabetes mellitus (%)	90 (28.3)	62 (28.2)	8 (23.5)	8 (26.7)	12 (35.3)	0.742
Hypertension (%)	160 (50.3.1)	116 (52.8)	13 (38.2)	13 (43.3)	18 (52.9)	0.365
Liver cirrhosis (%)	18 (5.6)	10 (4.5)	4 (11.7)	3 (10)	1 (2.9)	0.655
COPD (%)	4 (1.2)	2 (0.9)	1 (2.9)	0 (0)	1 (2.9)	0.455
Coronary artery disease (%)	78 (24.5)	53 (24.1)	9 (26.4)	6 (20)	10 (29.4)	0.713
CHF, NYHA I & II (%)	211 (66.3)	146 (66.3)	23 (67.6)	19 (63.3)	23 (67.6)	0.960
CHF, NYHA III & IV (%)	70 (22)	51 (23)	5 (15)	6 (20)	8 (23.5)	0.392
History of malignancy (%)	88 (27.6)	62 (28.2)	9 (26.5)	8 (26.7)	9 (26.5)	0.993
Surgery category
Abdominal surgery (%)	125 (39)	86 (39)	13 (38)	12 (40)	14 (41)	0.812
Neurosurgery (%)	19 (5.9)	10 (4.5)	3 (8.8)	2 (6.6)	4 (11.7)	0.470
Chest surgery (%)	25 (7.8)	18 (8.1)	2 (5.9)	2 (6.6)	3 (8.8)	0.789
Trauma (%)	32 (10.1)	24 (10.9)	3 (8.8)	3 (10)	2 (5.9)	0.412
Orthopedic surgery (%)	18 (5.7)	13 (5.9)	2 (5.8)	2 (6.6)	1 (2.9)	0.472
Peripheral vascular surgery (%)	13 (4.1)	11 (5)	2 (5.8)	0 (0)	0 (0)	0.341
Gynecologic surgery (%)	18 (5.7)	14 (6.3)	0 (0)	2 (6.6)	2 (5.9)	0.312
Multiple surgeries (%)	9 (2.8)	5 (2.3)	1 (2.9)	1 (3.3)	2 (5.9)	0.470
Head and neck surgery (%)	20 (6.2)	16 (7.2)	1 (2.9)	0 (0)	3 (8.8)	0.371
Other surgery (%)	39 (12.2)	23 (10.4)	7 (20.5)	6 (20)	3 (8.8)	0.197
Scoring system
APACHE II^+	8 (6–13)	8 (6–12)	9.5 (7–15)	9.5 (5–17)	10 (6–15)	<0.001***
MODS^+	4 (2–7)	4 (2–6)	4 (2–7)	5 (2–8)	6 (3–8)	<0.001***
SOFA^+	7 (4–9)	6 (4–8)	6.5 (4–11)	6.5 (3.5–8)	8 (5–11)	<0.001***
Severity of sepsis (non-sepsis/sepsis/   severe sepsis/septic shock)	7/48/144/119	6/37/96/81	0/6/12/16	0/3/19/8	1/2/17/14	0.290
KDIGO classification   (non-AKI/stages 1/2/3)	220/34/21/43	220/0/0/0	0/9/8/17	0/12/7/11	0/13/6/15	<0.001***
Serial renal function
Baseline creatinine (0.4–1.2 mg/dL)^+	1.6 (1.1–2.0)	1.6 (1.2–2.0)	1.8 (1.0–1.9)	1.2 (1.1–1.8)	1.3 (1.1–2.1)	0.001**
Creatinine at AKI onset (0.4–1.2 mg/dL)^+	2.1 (1.6–2.6)	2.0 (1.5–2.3)	2.1 (1.6–2.7)	2.2 (1.9–3.0)	2.7 (1.6–3.0)	0.002**
Creatinine at peak AKI (0.4–1.2 mg/dL)^+	2.5 (1.9–3.5)	2.1 (1.6–2.4)	3.3 (2.2–3.8)	3.2 (2.6–4.1)	3.2 (2.7–5.5)	<0.001***
Baseline BUN (8–12 mg/dL)	31.3 ± 18.5	33.0 ± 18.7	24.4 ± 15.8	25.6 ± 14.7	32.4 ± 22.1	0.050
BUN at ICU (8–12 mg/dL)	31.2 ± 18.2	30.8 ± 16.7	26.9 ± 21.5	29.0 ± 13.8	39.1 ± 24.7	<0.001***
BUN at AKI onset (8–12 mg/dL)	40.7 ± 37.6	37.3 ± 18.8	41.7 ± 22.8	47.6 ± 20.2	54.4 ± 27.3	<0.001***
Biochemical data and clinical characteristics on ICU admission, first day
Albumin (g/dL)	3.1 ± 0.7	3.1 ± 0.7	3.3 ± 0.7	3.2 ± 0.6	3.0 ± 0.7	0.076
Hemoglobin (g/dL)	11.4 ± 2.2	11.5 ± 1.9	10.6 ± 2.1	11.1 ± 2.3	11.4 ± 2.1	0.965
WBC count (×10^3/µL)	11.3 ± 6.0	11.2 ± 5.7	10.9 ± 5.8	11.1 ± 5.8	12.2 ± 6.3	0.549
Platelets (×10^9/L)	175 ± 106	190 ± 123	170 ± 105	162 ± 101	167 ± 111	0.567
ALT (U/L)	129 ± 291	100 ± 186	121 ± 267	189 ± 459	137 ± 356	0.217
Total bilirubin (mg/dL)	2.4 ± 5.4	1.9 ± 4.7	3.6 ± 8.0	4.3 ± 8.4	1.5 ± 1.2	0.056
Prothrombin time INR^+	1.3 (1.1–1.4)	1.2 (1.0–1.3)	1.3 (1.2–1.5)	1.7 (1.5–2.1)	1.2 (1.1–1.4)	<0.001***
Lactate (mg/dL)^+	4.1 (1.6–5.9)	3.8 (1.5–5.6)	5.3 (1.8–6.5)	4.6 (2.0–7.9)	4.7 (1.5–5.8)	0.554
Sodium (mEq/L)	140.0 ± 5.7	140.5 ± 5.7	139.6 ± 6.7	140.8 ± 5.9	138.7 ± 6.4	0.487
Potassium (mEq/L)	4.0 ± 0.6	4.0 ± 0.6	4.0 ± 0.8	3.9 ± 0.6	4.1 ± 0.6	0.695
Bicarbonate (mmol/L)	22.2 ± 4.8	22.3 ± 4.1	21.9 ± 6.7	22.1 ± 4.9	22.2 ± 5.0	0.875
Medicine prescribed at AKI onset
Use of diuretics (%)	171 (53.7)	105 (47.7)	21 (61.7)	20 (66.7)	25 (73.5)	<0.001***
Furosemide (%)	140 (44)	90 (41)	16 (47)	11 (37)	23 (67.6)	0.026*
Bumetanide (%)	27 (8.4)	14 (6.3)	5 (14.7)	4 (13.3)	4 (11.7)	0.226
Mannitol (%)	4 (1.2)	3 (1.3)	0 (0)	1 (3.3)	0 (0)	0.821
Spironolactone (%)	1 (0.3)	1 (0.4)	0 (0)	0 (0)	0 (0)	0.551
Use of vasoactives (%)	157 (49.3)	105 (47.7)	21 (61.7)	12 (40)	19 (55.9)	0.266
^IE at peak AKI	7.6 ± 19.6	6.8 ± 19.9	7.8 ± 11.8	10.6 ± 26.2	9.6 ± 16.4	0.696

Notes: ⁺Interquartile range: *p < 0.05, **p < 0.01, ***p < 0.001.

Statistical comparison uses an analysis of variance (ANOVA), chi-squared, Mann–Whitney U or Kruskal–Wallis tests.

BMI, body mass index; ICU, intensive care unit; AKI, acute kidney injury; COPD, chronic obstructive pulmonary disease; CHF, congestive heart failure; NYHA, New York Heart Association classification of heart failure; BUN, blood urea nitrogen; APACHE II, Acute Physiology and Chronic Health Evaluation II score; MODS, the Multiple Organ Dysfunction score; SOFA, the Sequential Organ Failure Assessment score; INR, international normalized ratio; ALT, alanine transaminase; WBC, white blood cells.

^IE (inotrope equivalent) = (dopamine + dobutamine) + milrinone × 15 + (epinephrine + norepinephrine + isoproterenol) × 100 in μg/kg/min.

Table 3. Patients’ data divided according to KDIGO stages and subdivided by tertiles of the AKI duration.

	Stage 1	Stage 2	Stage 3
ICU stay (days)	1st: 6.5 (2–16)	1st: 6 (1–29)	1st: 4 (2–11)
	2nd: 3 (1–10)	2nd: 9.5 (3–18)	2nd: 7 (4–14)
	3rd: 5 (3–13)	3rd: 24 (5–34)	3rd: 17 (14–29)
The least UO (mL/day)	1st: 1260 (780–2770)	1st: 1292 (660–2007)	1st: 1400 (665–2090)
	2nd: 1030 (485–1810)	2nd: 1625 (750–2780)	2nd: 1490 (1140–2920)
	3rd: 1170 (1010–1760)	3rd: 1700 (1095–2770)	3rd: 1520 (420–2590)
APACHE II	1st: 9 (6.5–10)	1st: 9 (5.7–19)	1st: 10 (7–16.5)
	2nd: 4.5 (3–11)	2nd: 8 (5–19)	2nd: 12 (11–21)
	3rd: 10 (3–16)	3rd: 6.5 (65.2–15.5)	3rd: 12 (7–15)
MODS	5 (3.5–7.5)	4.5 (2.2–5.75)	4 (1–9)
	4 (1.25–5)	4 (1–7)	8 (4–13)
	7 (3–8)	3.5 (2.5–5.25)	7 (5–8)
SOFA	7 (5.5–11.5)	7.5 (5–10.7)	6 (4–12)
	5.5 (2.5–8)	5 (3–7)	8 (5–15)
	7 (1–12.5)	8.5 (6–10)	9 (8–11)
Surgery category (n) GS/NS/CS//Os/T/GYN/V/M ENT/ot	1st: 4/1/1/0/0/0/1/0/0/2	1st: 3/0/0/0/0/0/1/1/0/3	1st: 6/2/1/2/3/0/0/0/1/2
	2nd: 5/1/1/0/2/0/0/0/0/3	2nd: 3/1/0/2/0/0/0/1/0/0	2nd: 4/0/1/0/1/2/0/0/0/3
	3rd: 3/2/2/1/0/1/0/1/1/2	3rd: 2/0/0/0/1/0/0/1/1/1	3rd: 9/2/1/0/1/1/0/0/1/0
Severity of sepsis (n) sepsis/severe sepsis/septic shock	1st: 2/2/5	1st: 1/3/4	1st: 3/7/7
	2nd: 1/6/5	2nd: 1/6/0	2nd: 1/7/3
	3rd: 1/8/3	3rd: 0/1/5	3rd: 1/8/6
In-hospital mortality (n)	1st: 6	1st: 3	1st: 8
	2nd: 2	2nd: 3	2nd: 9
	3rd: 3	3rd: 2	3rd: 11

Notes: ICU, intensive care unit; UO, urine output; AKI, acute kidney injury; APACHE II, Acute Physiology and Chronic Health Evaluation II score; MODS, the Multiple Organ Dysfuntion score; SOFA, the Sequential Organ Failure Assessment score; GS, abdominal surgery; NS, neurosurgery; CS, chest surgery; T, trauma; Os, orthopedic surgery; V, peripheral vascular surgery; M, multiple surgery; GYN, gynecologic surgery; ENT, head and neck surgery; ot, other surgery.

Figure 2. Cumulative survival rate for 318 postoperative patients based on their AKI stages and the different tertiles of AKI in each of the KDIGO stages. Cumulative survival curve according to AKI stages (A) and the different tertiles of AKI in each of the KDIGO stages (B–D). The overall in-hospital survival rates were significantly in (A), (B) and (D) (p < 0.001 by log-rank test).

Figure 3. Cumulative survival rate for 318 postoperative patients based on the tertiles of AKI and the different AKI stages in each of the tertiles. Cumulative survival curve according to tertiles of AKI stages (A) and the different stages of AKI in each of the tertiles (B–D). *p < 0.05 by log-rank test in (A) and (C).

Figure 4. The AUC of the ROC curve for in-hospital mortality according to AKI stage, duration and stage together with duration.

Table 4. Hazard ratios for in-hospital mortality, for different durations of AKI.

Parameter	HR (95% CI)	p-Value	HR (95% CI)	p-Value
	Model 1		Model 2
Non-AKI	1 (reference)	1 (reference)	1 (reference)	1 (reference)
1st tertile	9.82 (4.88–19.71)	<0.001**	8.22 (2.25–30.02)	<0.001**
2nd tertile	7.75 (3.71–16.18)	<0.001**	8.38 (2.36–29.78)	<0.001**
3rd tertile	3.14 (1.55–6.55)	0.002*	2.45 (0.692–8.49)	0.166
	Model 3		Model 4
Non-AKI	1 (reference)	1 (reference)	1 (reference)	1 (reference)
1st tertile	9.69 (2.98–31.52)	<0.001**	7.92 (1.79–35.06)	0.006*
2nd tertile	8.02 (2.33–27.66)	0.001*	6.68 (1.32–33.67)	0.021*
3rd tertile	2.04 (0.63–6.61)	0.234	1.68 (0.57–7.12)	0.476

Notes: Model 1: Univariate analysis; Model 2: Adjusted for underlying diseases, age, gender, need for a ventilator, emergent operation and baseline renal function; Model 3: Model 2 and severity of sepsis, the use of vasoactive drugs and diuretics, surgery category; Model 4: Model 3 and APACHE II, MODS, SOFA scores and peak KDIGO stage.

*p < 0.05, **p < 0.001.

AKI, acute kidney injury; CI, confidence interval.