Risk factors of chronic kidney disease in cisplatin-based hyperthermia intraperitoneal chemotherapy

Figures & data

Figure 1. Patient allocation flow diagram. Fifty-five patients completed the study. One patient was excluded for extreme dose of cisplatin due to primary tumor of mesothelioma, and another 2 patients were excluded for advanced CKD stage.

Figure 2. Distribution of primary neoplasms liocation in 55 patients received cisplatin-based HIPEC.

Table 1. Characteristics of patients with cisplatin-based HIPEC.

Characteristic	No.(%)
Gender
Male	18 (32.7)
Female	37 (67.3)
Age (years)	55.4 ± 11.3
Race (Asian)	55 (100)
BMI	23.8 ± 4.1
Baseline renal function (eGFR)	90.5 ± 20.4
Co-morbidity
Hypertension	12 (21.8)
Diabetes mellitus	7 (12.7)
Hyperlipidemia	3 (5.5)
Cardiopathy	2 (3.6)
COPD	1 (1.8)
Cirrhosis	3 (5.5)
Drugs and other agents during hospital course
Metformin	1 (1.8)
ACE inhibitor & ARB	2 (3.6)
Diuretics	24 (43.6)
NSAID	31 (56.4)
Aminoglycosides antibiotics	0 (0)

Table 2. Operative profile.

Surgery average profile	Overall (n = 55)	CKD group (n = 17)	Non-CKD group (n = 38)	p-value
Mean Cisplatin dose	94.45 ± 14.46	92.65 ± 11.87	95.26 ± 15.55	0.304
Median PCI (percentile range)	9 (3-15)	7 (2.5-13)	10.5 (3.25-15.75)	0.374
CC score				0.484
CC score 0 (%)	42 (76.4)	14 (82.4)	28 (73.7)
CC score 1 (%)	13 (23.6)	3 (17.6)	10 (26.3)
Duration of surgery (min)	647.1 ± 168.3	670.24 ± 135.14	634.76 ± 185.49	0.428
IO Blood loss (mL)	481.2 ± 754.8	618.24 ± 881.86	411.45 ± 713.93	0.482
IO Blood transfusion (unit)	1.65 ± 3.627	2.53 ± 4.125	1.26 ± 3.367	0.317
Maximum of IO temperature (°C)	38.4 ± 0.6	38.64 ± 0.59	38.21 ± 0.64	0.027
UO during HIPEC (mL/kg/hr)	1.93 ± 1.70	1.33 ± 1.20	2.19 ± 1.84	0.056
UO during operation (mL/kg/hr)	1.85 ± 1.13	1.56 ± 0.88	1.98 ± 1.21	0.184
Intraoperative complications
Tumor rupture (%)	2 (3.6)	1 (5.9)	1 (2.6)	0.562
Iatrogenic vessel injury (%)	10 (18.2)	6 (35.3)	4 (10.5)	0.036
Diaphragm perforation (%)	2 (3.6)	0 (0.0)	2 (5.3)	–
Bladder perforation (%)	2 (3.6)	1 (5.9)	1 (2.6)	0.562
Postoperative ICU stay	1.47 ± 1.12	1.59 ± 1.54	1.42 ± 0.89	0.613
Postoperative hospital stay	13.73 ± 8.20	12.41 ± 2.55	14.32 ± 9.7	0.431

CKD: chronic kidney disease; PCI: peritoneal cancer index; CC score: completeness of cytoreductive score; IO: intraoperative; UO: urine output; ICU: intensive care unit.

Table 3. Parameter associated to acute kidney injury after cisplatin based HIPEC Obesity, body mass index ≥ 27.

Parameter	Patient No. (n = 55)	Acute Kidney Injury (%)	Univariate Analysis			Multivariate Analysis
			Odds Ratio	95% CI	p	Odds Ratio	95% CI	p
Patient Demographics
Age ≥ 60 years	23	47.8	1.34	0.455 to 3.946	0.596
Male	18	44.4	1.05	0.338 to 3.265	0.933
Diabetes mellitus	7	85.7	10.00	1.112 to 89.905	0.040	18.72	1.335 to 262.465	0.030
Hypertension	12	66.7	3.38	0.875 to 13.021	0.077
Obesity	10	60.0	2.25	0.556 to 9.112	0.256
Hypoalbuminemia	7	57.1	1.87	0.376 to 9.275	0.445
Neoadjuvant chemotherapy	22	59.1	2.89	0.946 to 8.821	0.063
Carboplatin	12	58.3	2.141	0.583 to 7.859	0.251
Cisplatin	2	0	–	–	–
Oxaliplatin	8	87.5	12.353	1.399 to 109.07	0.024
Intraoperative
PCI ≥ 10	26	42.3	0.90	0.310 to 2.626	0.851
Laparoscopic HIPEC + CRS	22	31.8	0.44	0.142 to 1.356	0.153
Massive transfusion	6	66.7	2.90	0.484 to 17.377	0.244
Intraoperative Tmax ≥ 38.5°C	25	64.0	4.89	1.549 to 15.435	0.007	11.76	2.244 to 61.471	0.004
Low UO during operation	27	55.6	2.64	0.880 to 7.910	0.083
Low UO output during HIPEC	30	46.7	1.53	0.496 to 4.724	0.459
Sepsis	12	50.0	1.39	0.385 to 5.013	0.616
Complications	16	43.75	4.40	1.261 to 15.347	0.020	5.76	1.075 to 30.871	0.041
Post-operative
Contrast media	4	50.0	1.32	0.172 to 10.105	0.790
ACE inhibitor/ ARB	3	66.7	2.73	0.232 to 32.008	0.425
Statins	3	66.7	2.73	0.232 to 32.008	0.425
NSAID	5	40.0	0.85	0.130 to 5.529	0.864
Parecoxib	22	63.6	4.03	1.284 to 12.619	0.017	5.49	1.178 to 25.531	0.030

Diabetes mellitus was defined as diabetes symptoms plus a random venous plasma glucose concentration ≥ 11.1 mmol/l or a fasting plasma glucose concentration ≥ 7.0 mmol/l (whole blood ≥ 6.1 mmol/l) or two-hour plasma glucose concentration ≥ 11.1 mmol/l two hours after 75 g anhydrous glucose in an oral glucose tolerance test (OGTT). Hypertension was defined as average systolic blood pressure ≥ 140 mmHg, or when the average diastolic blood pressure ≥ 90 mmHg. Hyperlipidemia was defined as patient taking statin. Obesity was defined as BMI ≥ 27 kg/m². Cirrhosis was defined according to Child-Pugh score and CT imaging. Hypoalbuminemia was defined as serum albumin ≤ 3.5 mg/dl. Neoadjuvant chemotherapy was defined as complete neoadjuvant at least 4 times during past 3 months. Massive transfusion was defined as transfusion more than 10 units of blood during operation. Intraoperative maximum temperature was based on finding in Table 2. Oliguria was defined as average urine output less than 1.5 ml/kg/hr. Sepsis was defined as Surviving Sepsis Campaign guideline. Contrast medium defined as patient received contrast medium for complete evaluation within 1 week before surgery. Parecoxib was defined as patient receiving intravenous parecoxib during cisplatin based HIPEC. Massive transfusion, transfusion of ≥10 units of whole blood or red blood cells. Low urine output < 1.0 ml/kg/hr. PCI: peritoneal cancer index; ACE inhibitor: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor blocker.

Table 4. Parameter associated to chronic kidney disease after cisplatin-based HIPEC.

Parameter	Patient No. (n = 55)	Chronic kidney disease (%)	Univariate Analysis			Multivariate Analysis
			Odds Ratio	95% CI	p	Odds Ratio	95% CI	p
Patient Demographics
Age > 60 years	23	43.5	2.75	0.848 to 8.902	0.092
Male	18	33.3	1.04	0.315 to 3.450	0.947
Diabetes mellitus	7	57.1	3.24	0.640 to 16.382	0.155
Hypertension	12	50.0	2.58	0.695 to 9.605	0.157
Obesity	10	50.0	2.75	0.675 to 11.204	0.158
Hypoalbuminemia	7	42.9	1.65	0.328 to 8.309	0.544
Neoadjuvant chemotherapy	22	50.0	3.71	1.140 to 12.101	0.029	3.00	0.792 to 11.344	0.106
Carboplatin	12	50.0	2.58	0.695 to 9.605	0.157
Cisplatin	2	0	–	–	–
Oxaliplatin	8	62.5	4.36	0.909 to 20.901	0.066
Intra-operative
PCI ≥ 10	26	26.9	0.70	0.220 to 2.225	0.546
Laparoscopic HIPEC + CRS	22	22.7	0.52	0.151 to 1.750	0.287
Massive transfusion	6	66.7	5.00	0.821 to 30.461	0.081
Temperature max > 38.5°C	25	52.0	5.42	1.568 to 18.718	0.008	6.40	1.568 to 26.100	0.010
Low UO during operation	28	25.0	2.06	0.653 to 6.510	0.217
Low UO during HIPEC	22	18.2	3.00	0.812 to 11.081	0.099
Complications	16	18.75	3.33	0.973 to 11.415	0.055
Post-operative
Sepsis	12	41.7	1.65	0.441 to 6.166	0.458
Contrast medium	4	50.0	2.19	0.282 to 16.946	0.454
ACE inhibitor/ ARB	3	33.3	1.13	0.095 to 13.322	0.926
Statins	3	66.7	4.93	0.415 to 58.575	0.206
NSAID	5	40.0	1.42	0.215 to 9.333	0.717
Parecoxib	22	50.0	3.71	1.140 to 12.101	0.029	4.39	1.095 to 17.600	0.037

Figure 3. Postoperative eGFR reduction in parecoxib subgroup. Dash line, reduction of eGFR.