World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 13, Number 6, December 2022, pages 370-378

Acute Kidney Injury After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in a Portuguese Population

Figure 1. Flowchart of patient enrollment and study population. CRS/HIPEC: cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

**Table 1.** Demographic and Clinical Data of the Patients Who Underwent CRS/HIPEC
	All (n = 182)	AKI (n = 23)	Non-AKI (n = 159)	P value
Descriptive statistics are presented as mean ± SD, or number (percentage). P-value < 0.05 was considered to be statistically significant. AKI: acute kidney injury; BMI: body mass index; CC score: completeness of cytoreduction score; CKD: chronic kidney disease; DM: diabetes mellitus; ECOG-PS: Eastern Cooperative Oncology Group performance status; eGFR: estimated glomerular filtration rate; HF: heart failure; HIPEC: hyperthermic intraperitoneal chemotherapy; HTN: hypertension; ICU: intensive care unit; IQR: interquartile range; NSAID: non-steroidal anti-inflammatory drug; PCI: peritoneal cancer index; RAS: renin-angiotensin system; SD: standard deviation.
Gender male (%)	125 (68.7%)	15 (65.2%)	110 (69.2%)	0.701
Age (years) (mean ± SD)	58.0 ± 12.1	60.3 ± 11.9	57.7 ± 12.2	0.333
ECOG-PS, n (%)
0	151 (83.0%)	18 (78.3%)	133 (84.7%)	0.432
1	29 (15.9%)	5 (21.7%)	24 (15.3%)	0.432
≥ 2	0 (0%)			-
Unknown	2 (1.1%)	0 (0%)	2 (1.3%)	-
BMI (mean ± SD)	26.2 ± 5.6	26.7 ± 7.1	26.1 ± 5.2	0.643
CKD history	9 (4.9%)	4 (17.4%)	5 (3.1%)	0.016
Stage 1	0 (0%)	0 (0%)	0 (0%)	-
Stage 2	1 (11.1%)	1 (4.3%)	0 (0%)	0.126
Stage 3a	5 (55.6%)	3 (13.0%)	2 (1.3%)	0.015
Stage 3b	3 (33.3%)	0 (0%)	3 (1.9%)	1.000
Stage ≥ 4	0 (0%)	0 (0%)	0 (0%)	-
Baseline eGFR (CKD-EPI mL/min/1.73 m²) (mean ± SD)	91.3 ± 23	81.0 ± 29.8	92.6 ± 21.6	0.084
Cancer type
Colorectal	63 (34.6%)	7 (30.4%)	56 (35.4%)	0.638
Mucinous appendix	43 (23.6%)	1 (4.3%)	42 (26.6%)	0.018
Ovary	27 (14.8%)	7 (30.4%)	20 (12.7%)	0.025
Pseudomyxoma peritonei	20 (11.0%)	2 (8.7%)	18 (11.4%)	1.000
Mesothelioma	12 (6.6%)	4 (17.4%)	8 (5.1%)	0.026
Gastric	12 (6.6%)	2 (8.7%)	10 (6.3%)	0.670
Others	5 (2.7%)	0 (0%)	5 (3.1%)	1.00
Previous chemotherapy	59 (32.4%)	9 (39.1%)	50 (31.4%)	0.461
Previous chemotherapy agent
Platinum agent (%)	33 (18.1%)	6 (26.1%)	27 (17.5%)	0.326
Non-platinum agent (%)	21 (11.5%)	3 (13.0%)	18 (11.7%)	0.851
Unknown	5 (2.7%)	0 0%	5 (3.1%)	1.000
Comorbidity
None	110 (60.4%)	12 (52.2%)	98 (61.6%)	0.386
DM	25 (13.7%)	6 (26.1%)	19 (11.9%)	0.066
HTN	67 (36.8%)	10 (43.5%)	57 (35.8%)	0.478
HF	4 (2.2%)	1 (4.3%)	3 (1.9%)	0.420
PCI, mean ± SD	14 ± 9.3	16.4 ± 8.9	13.6 ± 9.3	0.193
CC (%)
0	137 (75.3%)	17 (77.3%)	120 (79.5%)	0.812
1	24 (13.2%)	2 (9.1%)	22 (14.6%)	0.743
2	11 (6.0%)	2 (9.1%)	9 (6.0%)	0.574
3	1 (0.5%)	1 (4.5%)	0 (0%)	0.127
Unknown	9 (4.9%)	1 (4.3%)	8 (5.0%)	1.000
Bleeding during procedure
≤ 200 mL	116 (63.7%)	14 (60.9%)	102 (64.6%)	0.731
> 200 mL	65 (35.7%)	9 (39.1%)	56 (35.4%)	0.731
Unknown	1 (0.5%)
HIPEC regimen (%)
Mitomycin	139 (76.4%)	12 (52.2%)	127 (80.4%)	0.003
Cisplatin	42 (23.1%)	11 (47.8%)	31 (19.6%)	0.003
Unknown	1 (0.5%)			-
Crystalloids reposition during procedure (mL) (mean ± SD)	3,946.4 ± 1,156.5	4,176.1 ± 913.0	3,912.7 ± 1,186.7	0.309
Hospitalization (days)
Mean ± SD	14.2 ±10.1	22.1 ± 17.8	13.1 ± 7.9	0.025
Average (IQR)	11 (9 - 15)	15 (11 - 28)	11 (9 - 13)	0.010
ICU admission	63 (34.6%)	8 (34.8%)	55 (34.6%)	0.986
ICU duration (days)
Mean ± SD	1.7 ± 1.05	2.6 ± 2.1	1.6 ± 0.8	0.195
Average (IQR)	1 (1 - 2)	2.5 (1.0 - 4.5)	1.0 (1.0 - 2.0)	0.570
Infection	54 (32.4%)	11 (47.8%)	48 (30.2%)	0.091
Medications
NSAIDs	21 (11.5%)	5 (21.7%)	16 (10.1%)	0.101
RAS	30 (16.5%)	4 (17.4%)	26 (16.4%)	1.000
Antibiotics	58 (31.9%)	12 (52.2%)	46 (28.9%)	0.025
Electrolyte disorders
Hypomagnesemia	84 (46.2%)	13 (65.0%)	71 (55.5%)	0.475
Hypophosphatemia	98 (53.8%)	9 (39.1%)	89 (57.4%)	0.118
Hypokalemia	41 (22.5%)	6 (26.1%)	35 (22.6%)	0.709
Hypocalcemia	22 (12.1%)	3 (17.6%)	19 (21.6%)	1.000
Hyponatremia	26 (14.3%)	6 (26.1%)	20 (12.8%)	0.091

Table 1. Demographic and Clinical Data of the Patients Who Underwent CRS/HIPEC

All (n = 182)

AKI (n = 23)

Non-AKI (n = 159)

P value

Descriptive statistics are presented as mean ± SD, or number (percentage). P-value < 0.05 was considered to be statistically significant. AKI: acute kidney injury; BMI: body mass index; CC score: completeness of cytoreduction score; CKD: chronic kidney disease; DM: diabetes mellitus; ECOG-PS: Eastern Cooperative Oncology Group performance status; eGFR: estimated glomerular filtration rate; HF: heart failure; HIPEC: hyperthermic intraperitoneal chemotherapy; HTN: hypertension; ICU: intensive care unit; IQR: interquartile range; NSAID: non-steroidal anti-inflammatory drug; PCI: peritoneal cancer index; RAS: renin-angiotensin system; SD: standard deviation.

Gender male (%)

125 (68.7%)

15 (65.2%)

110 (69.2%)

0.701

Age (years) (mean ± SD)

58.0 ± 12.1

60.3 ± 11.9

57.7 ± 12.2

0.333

ECOG-PS, n (%)

151 (83.0%)

18 (78.3%)

133 (84.7%)

0.432

29 (15.9%)

5 (21.7%)

24 (15.3%)

0.432

≥ 2

0 (0%)

Unknown

2 (1.1%)

0 (0%)

2 (1.3%)

BMI (mean ± SD)

26.2 ± 5.6

26.7 ± 7.1

26.1 ± 5.2

0.643

CKD history

9 (4.9%)

4 (17.4%)

5 (3.1%)

0.016

Stage 1

0 (0%)

Stage 2

1 (11.1%)

1 (4.3%)

0 (0%)

0.126

Stage 3a

5 (55.6%)

3 (13.0%)

2 (1.3%)

0.015

Stage 3b

3 (33.3%)

0 (0%)

3 (1.9%)

1.000

Stage ≥ 4

0 (0%)

Baseline eGFR (CKD-EPI mL/min/1.73 m²) (mean ± SD)

91.3 ± 23

81.0 ± 29.8

92.6 ± 21.6

0.084

Cancer type

Colorectal

63 (34.6%)

7 (30.4%)

56 (35.4%)

0.638

Mucinous appendix

43 (23.6%)

1 (4.3%)

42 (26.6%)

0.018

Ovary

27 (14.8%)

7 (30.4%)

20 (12.7%)

0.025

Pseudomyxoma peritonei

20 (11.0%)

2 (8.7%)

18 (11.4%)

1.000

Mesothelioma

12 (6.6%)

4 (17.4%)

8 (5.1%)

0.026

Gastric

12 (6.6%)

2 (8.7%)

10 (6.3%)

0.670

Others

5 (2.7%)

0 (0%)

5 (3.1%)

1.00

Previous chemotherapy

59 (32.4%)

9 (39.1%)

50 (31.4%)

0.461

Previous chemotherapy agent

Platinum agent (%)

33 (18.1%)

6 (26.1%)

27 (17.5%)

0.326

Non-platinum agent (%)

21 (11.5%)

3 (13.0%)

18 (11.7%)

0.851

Unknown

5 (2.7%)

0 0%

5 (3.1%)

1.000

Comorbidity

None

110 (60.4%)

12 (52.2%)

98 (61.6%)

0.386

25 (13.7%)

6 (26.1%)

19 (11.9%)

0.066

HTN

67 (36.8%)

10 (43.5%)

57 (35.8%)

0.478

4 (2.2%)

1 (4.3%)

3 (1.9%)

0.420

PCI, mean ± SD

14 ± 9.3

16.4 ± 8.9

13.6 ± 9.3

0.193

CC (%)

137 (75.3%)

17 (77.3%)

120 (79.5%)

0.812

24 (13.2%)

2 (9.1%)

22 (14.6%)

0.743

11 (6.0%)

2 (9.1%)

9 (6.0%)

0.574

1 (0.5%)

1 (4.5%)

0 (0%)

0.127

Unknown

9 (4.9%)

1 (4.3%)

8 (5.0%)

1.000

Bleeding during procedure

≤ 200 mL

116 (63.7%)

14 (60.9%)

102 (64.6%)

0.731

> 200 mL

65 (35.7%)

9 (39.1%)

56 (35.4%)

0.731

Unknown

1 (0.5%)

HIPEC regimen (%)

Mitomycin

139 (76.4%)

12 (52.2%)

127 (80.4%)

0.003

Cisplatin

42 (23.1%)

11 (47.8%)

31 (19.6%)

0.003

Unknown

1 (0.5%)

Crystalloids reposition during procedure (mL) (mean ± SD)

3,946.4 ± 1,156.5

4,176.1 ± 913.0

3,912.7 ± 1,186.7

0.309

Hospitalization (days)

Mean ± SD

14.2 ±10.1

22.1 ± 17.8

13.1 ± 7.9

0.025

Average (IQR)

11 (9 - 15)

15 (11 - 28)

11 (9 - 13)

0.010

ICU admission

63 (34.6%)

8 (34.8%)

55 (34.6%)

0.986

ICU duration (days)

Mean ± SD

1.7 ± 1.05

2.6 ± 2.1

1.6 ± 0.8

0.195

Average (IQR)

1 (1 - 2)

2.5 (1.0 - 4.5)

1.0 (1.0 - 2.0)

0.570

Infection

54 (32.4%)

11 (47.8%)

48 (30.2%)

0.091

Medications

NSAIDs

21 (11.5%)

5 (21.7%)

16 (10.1%)

0.101

RAS

30 (16.5%)

4 (17.4%)

26 (16.4%)

1.000

Antibiotics

58 (31.9%)

12 (52.2%)

46 (28.9%)

0.025

Electrolyte disorders

Hypomagnesemia

84 (46.2%)

13 (65.0%)

71 (55.5%)

0.475

Hypophosphatemia

98 (53.8%)

9 (39.1%)

89 (57.4%)

0.118

Hypokalemia

41 (22.5%)

6 (26.1%)

35 (22.6%)

0.709

Hypocalcemia

22 (12.1%)

3 (17.6%)

19 (21.6%)

1.000

Hyponatremia

26 (14.3%)

6 (26.1%)

20 (12.8%)

0.091

**Table 2.** Analysis of Risk Factors for the Occurrence of AKI Using Univariate Logistic Regression Models
	OR (95% CI)	P value
P-value < 0.05 was considered to be statistically significant. AKI: acute kidney disease; CI: confidence interval; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; HIPEC: hyperthermic intraperitoneal chemotherapy; ICU: intensive care unit; OR: odds ratio.
DM	0.39 (0.14 - 1.09)	0.074
Previous CKD	0.15 (0.38 - 0.62)	0.009
Baseline eGFR (CKD-EPI mL/min/1.73 m²)	1.02 (1.00 - 1.04)	0.029
Antibiotics	0.37 (0.15 - 0.91)	0.029
Days in ICU	2.06 (1.11 - 3.82)	0.022
Hospitalization (duration)	1.06 (0.02 - 0.11)	0.010
HIPEC protocol
Cisplatin	3.76 (1.52 - 9.31)	0.040

Table 2. Analysis of Risk Factors for the Occurrence of AKI Using Univariate Logistic Regression Models

OR (95% CI)

P value

P-value < 0.05 was considered to be statistically significant. AKI: acute kidney disease; CI: confidence interval; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; HIPEC: hyperthermic intraperitoneal chemotherapy; ICU: intensive care unit; OR: odds ratio.

0.39 (0.14 - 1.09)

0.074

Previous CKD

0.15 (0.38 - 0.62)

0.009

Baseline eGFR (CKD-EPI mL/min/1.73 m²)

1.02 (1.00 - 1.04)

0.029

Antibiotics

0.37 (0.15 - 0.91)

0.029

Days in ICU

2.06 (1.11 - 3.82)

0.022

Hospitalization (duration)

1.06 (0.02 - 0.11)

0.010

HIPEC protocol

Cisplatin

3.76 (1.52 - 9.31)

0.040

**Table 3.** Analysis of Risk Factors for the Occurrence of AKI Using Multivariable Logistic Regression Models
	OR (95% CI)	P value
P-value < 0.05 was considered to be statistically significant. AKI: acute kidney disease; CI: confidence interval; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; eGFR: estimated glomerular filtration rate; HIPEC: hyperthermic intraperitoneal chemotherapy; ICU: intensive care unit; OR: odds ratio.
eGFR previous HIPEC (CKD-EPI mL/min/1.73 m²)	0.96 (0.94 - 0.98)	0.037
Days in ICU	2.42 (1.07 - 5.45)	0.033
HIPEC protocol
Cisplatin	12.21 (1.26 - 109.70)	0.025
Mitomycin	Ref

Table 3. Analysis of Risk Factors for the Occurrence of AKI Using Multivariable Logistic Regression Models

OR (95% CI)

P value

P-value < 0.05 was considered to be statistically significant. AKI: acute kidney disease; CI: confidence interval; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; eGFR: estimated glomerular filtration rate; HIPEC: hyperthermic intraperitoneal chemotherapy; ICU: intensive care unit; OR: odds ratio.

eGFR previous HIPEC (CKD-EPI mL/min/1.73 m²)

0.96 (0.94 - 0.98)

0.037

Days in ICU

2.42 (1.07 - 5.45)

0.033

HIPEC protocol

Cisplatin

12.21 (1.26 - 109.70)

0.025

Mitomycin

Ref