Risk factors of acute renal impairment after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Figures & data

Figure 1. Flowchart of patient enrollment and study population. CC: completeness of cytoreduction score; CRS/HIPEC: cytoreductive surgery with hyperthermic intraperitoneal chemotherapy; ECOG: Eastern Cooperative Oncology Group (ECOG) performance status; ESRD: end-stage renal disease; ARI: acute renal impairment.

Table 1. Demographic and clinical data of the patients who underwent CRS/HIPEC.

Characteristic	All (n = 169)	ARI Group (n = 21)	Non-ARI Group (n = 148)	p-value
Age (years)				0.373
Mean ± SD	54.26 ± 12.14	56.48 ± 10.56	53.95 ± 12.35
Sex				0.177
Male	54 (32.0%)	4 (19.0%)	50 (33.8%)
Female	115 (68.0%)	17 (81.0%)	98 (66.2%)
BMI (kg/m^2)				0.855
Mean ± SD	23.68 ± 4.17	23.52 ± 3.43	23.70 ± 4.27
ECOG				0.442
0–1	165 (97.6%)	20 (95.2%)	145 (98.0%)
2	4 (2.4%)	1 (4.8%)	3 (2.0%)
ASA classification				0.539
2	99 (58.6%)	11 (52.4%)	88 (59.5%)
3	70 (41.4%)	10 (47.6%)	60 (40.5%)
Clinical presentation				0.305
Primary	98 (58.0%)	10 (47.6%)	88 (59.5%)
Recurrence	71 (42.0%)	11 (52.4%)	60 (40.5%)
Medication before HIPEC:
NSAID	6 (3.6%)	2 (9.5%)	4 (2.7%)	0.115
RAS	3 (1.8%)	0 (0%)	3 (2%)	1.000
Previous definitive surgery				0.337
None	81 (47.9%)	8 (38.1%)	73 (49.3%)
Yes	88 (52.1%)	13 (61.9%)	75 (50.7%)
Previous systemic therapy				0.021*
Never	53 (31.4%)	4 (19.0%)	49 (33.1%)
1st line	57 (33.7%)	4 (19.0%)	53 (35.8%)
2nd lines or more	59 (34.9%)	13 (61.9%)	46 (31.1%)
Previous chemotherapy				0.007*
Platinum based	61 (36.1%)	14 (66.7%)	47 (31.8%)
Others	54 (32.0%)	4 (19.0%)	50 (33.8%)
Never received chemotherapy	54 (32.0%)	3 (14.3%)	51 (34.5%)
Preoperative PCI				0.768
Mean ± SD	10.52 ± 10.27	11.14 ± 7.90	10.43 ± 10.58
CC score				0.862
0	119 (70.4%)	15 (71.4%)	104 (70.3%)
1	25 (14.8%)	4 (19.0%)	21 (14.2%)
2	12 (7.1%)	1 (4.8%)	11 (7.4%)
3	13 (7.7%)	1 (4.8%)	12 (8.1%)
Enrollment indications				0.589
Palliative	18 (10.7%)	2 (9.5%)	16 (10.8%)
Curative	113 (66.9%)	16 (76.2%)	97 (65.5%)
Prophylactic	38 (22.5%)	3 (14.3%)	35 (23.6%)
Cancer				0.04*
Colorectal	54 (32.0%)	5 (23.8%)	49 (33.1%)
Ovary	60 (35.5%)	13 (61.9%)	47 (31.8%)
Gastric	30 (17.8%)	1 (4.8%)	29 (19.6%)
Mesothelioma	2 (1.2%)	1 (4.8%)	1 (0.7%)
Pseudomyxoma peritonei	16 (9.5%)	1 (4.8%)	15 (10.1%)
Others	7 (4.1%)	0 (0%)	7 (4.7%)
Comorbidity
Hypertension	45 (26.6%)	4 (19.0%)	41 (27.7%)	0.402
Diabetes mellitus	29 (17.2%)	5 (23.8%)	24 (16.2%)	0.389
Surgical method				0.562
Laparotomy	137 (81.1%)	18 (85.7%)	119 (80.4%)
Laparoscopy	32 (18.9%)	3 (14.3%)	29 (19.6%)
Blood loss (mL)				0.923
<500	146 (86.4%)	18 (85.7%)	128 (86.5%)
≥500	23 (13.6%)	3 (14.3%)	20 (13.5%)
HIPEC regimen				0.004*
Cisplatin	71 (42.0%)	15 (71.4%)	56 (37.8%)
Non-cisplatin	98 (58.0%)	6 (28.6%)	92 (62.2%)
HIPEC perfusate				0.247
normal saline	10 (5.9%)	1 (4.8%)	9 (6.1%)
normal saline and pentastarch	83 (49.1%)	7 (33.3%)	76 (51.4%)
peritoneal dialysis solution	76 (45.0%)	13 (61.9%)	63 (42.6%)
HIPEC duration (min)				0.693
≤60	112 (66.3%)	15 (71.5%)	97 (65.5%)
>60	57 (33.7%)	6 (28.6%)	51 (34.5%)

Descriptive statistics are presented as mean ± SD, or number (percentage).

SD: standard deviation; BMI: body mass index; ECOG: Eastern Cooperative Oncology Group performance status; PCI: peritoneal cancer index; CC score: completeness of cytoreduction score; CRS/HIPEC: cytoreductive surgery and hyperthermic intraperitoneal chemotherapy; NSAID: non-steroidal anti- inflammatory drug; RAS: renin-angiotensin system antihypertensive medication; ASA classification: the American Society of Anesthesiologists physical status classification; ARI: acute renal impairment.

*p-value <0.05 was considered to be statistically significant.

Table 2. Analysis of risk factors for the occurrence of ARI using simple logistic regression models.

Crude OR (95% CI)		p-value
Age (years)
≥55	1.33 (0.53, 3.35)	0.541
<55	1
Sex
Female	2.17 (0.69, 6.79)	0.180
Male	1
ECOG performance status
1 or 2	2.37 (0.87, 6.44)	0.091
0	1
ASA classification
2	0.750 (0.30, 1.88)	0.539
3	1
Previous NSAIDs
Yes	3.79 (0.65, 22.10)	0.139
No	1
Previous definitive surgery
Yes	1.58 (0.62, 4.04)	0.338
None	1
Previous systemic therapy
Any	3.16 (0.89, 11.22)	0.076
Never	1
Previous platinum exposure
Yes	4.30 (1.63, 11.35)	0.003*
No	1
PCI score
8 ∼ 39	1.63 (0.64, 4.15)	0.310
1 ∼ 7	1
Cancer type
Ovary	3.49 (1.36, 9.00)	0.010*
Others	1
Enrolled indications
Palliative	1.46 (0.22, 9.60)	0.695
Curative	1.92 (0.53, 7.01)	0.321
Prophylactic	1
Comorbidity
Hypertension
Yes	0.61 (0.20, 1.93)	0.405
No	1
Diabetes mellitus
Yes	1.62 (0.54, 4.83)	0.391
No	1
Blood loss (mL)
≥500	1.07 (0.29, 3.95)	0.923
<500	1
HIPEC regimen
Cisplatin	4.11 (1.51, 11.20)	0.006*
Non-cisplatin	1
HIPEC perfusate
Peritoneal dialysis solution	2.19 (0.86, 5.61)	0.101
Normal saline-based solution	1
HIPEC duration
>60 min	0.761 (0.28, 2.08)	0.594
≤60 min	1
Pre-hydration
≤2000 ml	1.52 (0.58, 4.00)	0.392
>2000 ml	1

ARI: acute renal impairment; OR: odds ratio; CI: confidence interval; ECOG: Eastern Cooperative Oncology Group; PCI: peritoneal cancer index; HIPEC: hyperthermic intraperitoneal chemotherapy; NSAIDs: non-steroidal anti-inflammatory drugs; ASA classification: the American Society of Anesthesiologists physical status classification.

*p-value <0.05 was considered to be statistically significant.

Table 3. Analysis of risk factors for the occurrence of ARI using simple logistic regression models (postoperative day 1 serum electrolytes and albumin level).

Serum data	OR (95% CI)	p-value
Albumin (g/dL)
Hypo	1.01 (0.40, 2.55)	0.980
Normal (3.5)	1
Na (mEq/L)
Hypo	1.60 (0.49, 5.26)	0.441
Normal (134)	1
K (mEq/L)
Hypo	0.62 (0.24, 1.63)	0.333
Normal (3.6)	1
Ca (mg/dL)
Hypo	0.84 (0.33, 2.10)	0.703
Normal (7.9)	1
Mg (mEq/L)
Hypo	1.07 (0.43, 2.70)	0.881
Normal (1.3)	1

OR: odds ratio; CI: confidence interval; Na: sodium; K: potassium; Ca: calcium; Mg: magnesium; Hypo: lower than normal lower limit; Normal: normal lower limit.

Table 4. Analysis of risk factors for the occurrence of ARI using multiple logistic regression models.

	Adjusted OR (95% CI)	p-value
Age (years)
≥55	2.54 (0.86, 7.49)	0.091
<55	1
Sex
Female	1.42 (0.42, 4.84)	0.573
Male	1
HIPEC regimen
Cisplatin	11.38 (3.07, 42.13)	<0.001*
Non-cisplatin	1
HIPEC perfusate
Peritoneal dialysis solution	7.07 (2.06, 24.26)	0.002*
Normal saline-based solution	1

ARI: acute renal impairment; OR: odds ratio; CI: confidence interval; HIPEC: hyperthermic intraperitoneal chemotherapy.

*p-value <0.05 was considered to be statistically significant.

Table 5. Descriptive statistics of kidney function in the 21 ARI patients.

	Grade 1 (n = 14)	Grade 2 (n = 4)	Grade 3 (n = 2)	Grade 4 (n = 1)
Max creatinine
Median (min.–max.)	1.16 (1.06–1.51)	1.96 (1.55–2.87)	4.51 (3.54, 5.48)	6.34
Days of max creatinine (within 7 days)
Median (min.–max.)	3 (1–7)	7 (1–7)	7	7
Days of elevated creatinine > Grade 1
Median (min.–max.)	3 (1–7)	5.5 (1–7)	4	1
Days to recover to normal creatinine
Median (min.–max.)	15.5 (3–76)	46 (7–87)	x	x
Cisplatin as HIPEC regimen (n)	9 (64.3%)	3 (75%)	Yes (50,100 mg/m^2)	Yes (75 mg/m^2)

Max.: maximum; min.: minimum; x: no recovery; ARI: acute renal impairment.