A prospective pilot study of kidney-specific biomarkers to detect acute kidney injury after cytoreduction and hyperthermic intraperitoneal chemotherapy

Chen, Chao-Yu; Wang, Ting-Yao; Chang, Hung-Yu; Chen, Min-Chi; Yang, Lan-Yan

doi:10.2478/abm-2024-0034

Figures & Tables

Flowchart of patient enrollment and study population. AKI, acute kidney injury; CRS/HIPEC, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Comparisons of the AKI and non-AKI groups. (A, C, E) The ranges of urine NGAL, sCyC, and sβ2-MG between baseline and day 1. (B, D, F) The ranges of urine NGAL, sCyC, and sβ2-MG between baseline and day 3. AKI, acute kidney injury; NGAL, neutrophil gelatinase-associated lipocalin; sCyC, serum cystatin C; sβ2-MG, serum β2 microglobulin.

Comparisons of patients without previous chemotherapy treatment (non-previous-trt group) and patients with previous chemotherapy treatment (previous-trt group). (A, C, E) The ranges of urine NGAL, sCyC, and sβ2-MG between baseline and day 1. (B, D, F) The ranges of urine NGAL, sCyC, and sβ2-MG between baseline and day 3. NGAL, neutrophil gelatinase-associated lipocalin; sCyC, serum cystatin C; sβ2-MG, serum β2 microglobulin.

Comparisons of patients who received non-cisplatin HIPEC regimens (non-cisplatin group) and patients who received cisplatin HIPEC regimens (cisplatin group). (A, C, E) The ranges of urine NGAL, sCyC, and sβ2-MG between baseline and day 1. (B, D, F) The ranges of urine NGAL, sCyC, and sβ2-MG between baseline and day 3. HIPEC, hyperthermic intraperitoneal chemotherapy; NGAL, neutrophil gelatinase-associated lipocalin; sCyC, serum cystatin C; sβ2-MG, serum β2 microglobulin.

ROC analysis curve showing the range values on day 3 for each study's biomarker to detect AKI. AKI, acute kidney injury; ROC, receiver operating characteristic; sCyC, serum cystatin C; sβ2-MG, serum β2 microglobulin.

Demographic and clinical data of the patients enrolled in the analysis (n = 75)

Characteristics	All (n = 75)	AKI group (n = 5)	Non-AKI group (n = 70)	P
Demographics

Age (years)				0.941
Median (min, max)	60 (22, 74)	55 (48, 68)	60 (22, 74)
Sex				>0.999
Male	28 (37.3%)	2 (40.0%)	26 (37.1%)
BMI (kg/m²)				0.082
Median (min, max)	24.5 (13, 37)	26.3 (25, 29)	24.2 (13, 37)

Baseline clinical data

ECOG				>0.999
0–1	71 (94.7%)	5 (100%)	66 (94.3%)
2	4 (5.3%)	0 (0%)	4 (5.7%)
Clinical presentation				0.653
Primary	49 (65.3%)	4 (80.0%)	45 (64.3%)
Recurrence	26 (34.7%)	1 (20.0%)	25 (35.7%)
Medication before HIPEC
NSAID	2 (2.7%)	1 (20.0%)	1 (1.4%)	0.130
RAS	4 (5.3%)	1 (20.0%)	3 (4.3%)	0.246
Previous definitive surgery				0.386
None	43 (57.3%)	4 (80.0%)	39 (56.3%)
Previous systemic therapy				0.093
Never	27 (36.0%)	1 (20.0%)	26 (37.1%)
First line	27 (36.0%)	4 (80.0%)	23 (32.9%)
Two lines or more	21 (28.0%)	0 (0%)	21 (30.0%)
Previous chemotherapy				0.380
Platinum-based	24 (32.0%)	3 (60.0%)	21 (30.0%)
Other chemotherapy	24 (32.0%)	1 (20.0%)	23 (32.9%)
Never received chemotherapy	27 (36.0%)	1 (20.0%)	26 (37.1%)
Preoperative PCI				>0.999
Median (min, max)	6 (0, 39)	6 (0, 25)	6 (0, 39)
CC score				0.066
0	57 (76.0%)	4 (80.0%)	53 (75.7%)
1	10 (13.3%)	0 (0%)	10 (14.3%)
2	2 (2.7%)	1 (20.0%)	1 (1.4%)
3	6 (8.0%)	0 (0%)	6 (8.6%)
Enrollment indications				0.744
Adjuvant	16 (21.3%)	1 (20.0%)	15 (21.4%)
Curative	52 (69.3%)	4 (80.0%)	48 (68.6%)
Palliation	7 (9.3%)	0 (0%)	7 (10.0%)
Cancer				0.431
Ovary	23 (30.7%)	3 (60.0%)	20 (28.6%)
Colorectal	17 (22.7%)	0 (0%)	17 (24.3%)
Gastric	27 (36.0%)	1 (20.0%)	26 (37.1%)
Pseudomyxoma peritonei	7 (9.3%)	1 (20.0%)	6 (8.6%)
Others	1 (1.3%)	0 (0%)	1 (1.4%)
Comorbidity
Hypertension	18 (24.0%)	2 (40.0%)	16 (22.9%)	0.588
Diabetes mellitus	15 (20.0%)	2 (40.0%)	13 (18.6%)	0.260
Hepatitis B or C	16 (21.3%)	1 (20.0%)	15 (21.4%)	>0.999

CRS/HIPEC parameters

Surgical method				>0.999
Laparotomy	66 (88.0%)	5 (100%)	61 (87.1%)
Laparoscopy	9 (12.0%)	0 (0%)	9 (12.9%)
Blood loss (mL)				0.558
<500	64 (85.3%)	4 (80.0%)	60 (85.7%)
≥500	11 (14.7%)	1 (20.0%)	10 (14.3%)
HIPEC regimen				0.079
Cisplatin	45 (60.0%)	5 (100%)	40 (57.1%)
Non-cisplatin	30 (40.0%)	0 (0%)	30 (42.9%)
HIPEC perfusate				0.313
Normal saline and pentastarch	53 (70.7%)	5 (100%)	49 (68.6%)
Peritoneal dialysis solution	22 (29.3%)	0 (0%)	22 (31.4%)
HIPEC duration (min)				0.582
≤60	58 (77.3%)	5 (100%)	53 (75.7%)
>60	17 (22.7%)	0 (0%)	17 (24.3%)

Serial measurements of renal markers and electrolytes

Biomarkers		AKI group (N = 5)	Non-AKI group (N = 70)	P
sCreat (mg/dL)	Baseline	1.02 (0.69–1.21)	0.78 (0.42–1.24)	0.025^*
	Post-OP day 1	0.97 (0.70–1.07)	0.74 (0.37–1.34)	0.086
	Post-OP day 3	1.17 (0.55–1.88)	0.62 (0.34–1.25)	0.014^*
	Post-OP day 7	2.34 (1.49–9.90)	0.67 (0.30–1.49)	0.004^*
Urine NGAL (ng/mL)	Baseline	10 (10–77.90)	10 (0.30–344.70)	0.570
	Post-OP 2 h	10 (10–32.70)	10.45 (2.90–287.70)	0.416
	Post-OP day 1	10 (10–47.20)	13.45 (3.20–2175.10)	0.254
	Post-OP day 2	10 (10–37.40)	1.47 (2.80–2260.20)	0.478
	Post-OP day 3	10 (10–29.90)	12.25 (2.20–499)	0.696
	Post-OP day 7	16.10 (10.00–20.40)	14.75 (0.80–234.20)	0.562
sCyC(mg/L)	Baseline	1.01 (0.56–1.44)	0.76 (0.40–1.67)	0.066
	Post-OP 2 h	0.69 (0.50–0.76)	0.60 (0.40–1.30)	0.840
	Post-OP day 1	0.71 (0.58–0.88)	0.63 (0.40–1.55)	0.663
	Post-OP day 2	0.83 (0.76–1.24)	0.80 (0.48–1.96)	0.135
	Post-OP day 3	1.17 (0.79–1.27)	0.82 (0.55–1.98)	0.053
	Post-OP day 7	1.38 (0.64–1.63)	0.80 (0.50–1.70)	0.151
Serum β2-microglobulin (ng/mL)	Baseline	1782 (1139–2466)	1449.5 (764–3550)	0.196
	Post-OP 2 h	1381 (1047–1437)	1267.5 (756–3063)	0.857
	Post-OP day 1	1301 (1131–3594)	1279 (694–3574)	0.370
	Post-OP day 2	1414 (1298–1827)	1267 (773–3726)	0.123
	Post-OP day 3	1802 (1452–1880)	1346.50 (865–3336)	0.025^*
	Post-OP day 7	1649 (1168–2586)	1466 (722–3585)	0.533
Serum sodium (mEq/L)	Baseline	141 (136–144)	140 (126–145)	0.804
	Post-OP day 1	137 (135–137)	137 (128–143)	0.662
	Post-OP day 3	137 (132–142)	137 (126–142)	0.804
	Post-OP day 7	131 (125–135)	135 (118–141)	0.024^*
Serum potassium (mEq/L)	Baseline	3.70 (3.60–4.10)	4.00 (3.30–4.80)	0.121
	Post-OP day 1	3.80 (3.30–3.90)	3.70 (2.60–4.90)	0.890
	Post-OP day 3	2.90 (2.80–3.90)	3.90 (3.10–5.20)	0.004^*
	Post-OP day 7	4.30 (2.50–4.90)	3.70 (2.50–5.10)	0.224
Serum magnesium (mEq/L)	Baseline	1.61 (1.51–1.67)	1.64 (1.22–2.21)	0.668
	Post-OP day 1	1.27 (0.91–1.65)	1.42 (0.94–1.71)	0.680
	Post-OP day 3	1.56 (1.22–1.71)	1.57 (1.21–2.05)	0.422
	Post-OP day 7	1.38 (1.16–1.81)	1.47 (0.92–1.88)	0.931
Serum calcium (mEq/L)	Baseline	8.80 (8.70–9.40)	8.85 (7.20–9.70)	0.775
	Post-OP day 1	7.60 (7.00–8.40)	7.90 (6.50–8.70)	0.049
	Post-OP day 3	8.10 (7.80–8.60)	8.30 (7.00–9.40)	0.439
	Post-OP day 7	8.30 (6.90–8.70)	8.40 (7.20–9.70)	0.427
Serum albumin (g/dL)	Baseline	4.45 (4.10–4.70)	4.20 (2.00–4.80)	0.148
	Post-OP day 1	4.10 (3.00–4.50)	3.60 (1.50–4.40)	0.187
	Post-OP day 3	3.70 (3.00–4.20)	3.60 (2.10–4.40)	0.771
	Post-OP day 7	3.40 (2.70–4.00)	3.60 (1.80–4.60)	0.452

A prospective pilot study of kidney-specific biomarkers to detect acute kidney injury after cytoreduction and hyperthermic intraperitoneal chemotherapy

Figures & Tables

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Figure 5.

Demographic and clinical data of the patients enrolled in the analysis (n = 75)

Serial measurements of renal markers and electrolytes

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