Supplemental Table S1. Baseline characteristics and perioperative parameters between patients with and without hydroxyethyl starch during surgery before propensity score matching.
Characteristics HES group
(n=326) Non-HES group
(n=780) P-value Standardized difference d
Demographic data
Age, years 58 (49, 68) 56 (48, 65) 0.005 0.180
Female, n 81 (24.8) 242 (31.0) 0.047 -0.143
Body-mass index, kg/m² 24.7 (22.6, 27.0) 24.4 (22.5, 26.4) 0.057 0.097
Current smoker, n 50 (15.3) 118 (15.1) 1.000 0.006
Background medical status
ASA physical status classification 1/
2/ 3/4 129 (39.6)/ 166 (50.9)/
30 (9.2)/ 1 (0.3) 380 (48.7)/ 358 (45.9)/ 41
(5.3)/ 1 (0.1) 0.010
ASA class III or IV 31 (9.5) 42 (5.4) 0.017 0.140
Hypertension, n 166 (50.9) 313 (40.1) 0.001 0.216
Diabetes mellitus, n 69 (21.2) 104 (13.3) 0.001 0.191
Cerebrovascular accident, n 10 (3.1) 15 (1.9) 0.344 0.066
Ischemic heart disease, n 6 (1.8) 9 (1.2) 0.539 0.051
Liver disease, na 16 (4.9) 30 (3.8) 0.521 0.049
Hyperlipidemia, n 38 (11.7) 65 (8.3) 0.105 0.103
Preoperative eGFR, mL/min/1.73m2 77.4 (63.9, 91.3) 81.0 (70.2, 92.6) 0.007 -0.128
Preoperative stage of CKD < 0.001
1 (eGFR ≥ 90 mL/min/m2) 87 (26.7) 231 (29.6)
2 (eGFR 60 – 89 mL/min/1.73m2) 174 (53.4) 461 (59.1)
3a (45 – 59 mL/min/1.73m2) 39 (12.0) 45 (5.8)
3b (30 – 44 mL/min/1.73m2) 10 (3.1) 14 (1.8)
4 (15 – 29 mL/min/1.73m2) 5 (1.5) 1 (0.1)
5 (< 15 mL/min/1.73m2) 11 (3.4) 28 (3.6)
Preoperative proteinuria, n 41 (12.6) 50 (6.4) 0.001 0.186
Preoperative hemoglobin, g/dL 13.6 (12.3, 14.8) 13.9 (12.6, 14.9) 0.067 -0.128
Preoperative albumin, g/dL 4.4 (4.1, 4.6) 4.4 (4.2, 4.6) 0.006 -0.174
ECOG performance status (n=1105) 0.295
0/ 1/ 2/ 3 275 (84.4)/ 38 (11.7)/
12 (3.7)/ 1 (0.3)
682 (87.5)/ 79 (10.1)/ 15 (1.9)/ 3 (0.4)
Clinical stage < 0.001 0.278
T1a / 1b 201/46 562/121
T2a / 2b 40/14 69/8
T3a / 3b / 3c 10/7/8 9/6/5
N 0/1 304/22 757/23 0.006 0.151
M 0/1 302/24 758/22 0.001 0.173
Operation and anesthesia related Operation year,
2010/2011/2012/2013/2014 43/95/86/78/24 116/206/192/169/97 0.121 -0.063
Surgery type 0.165 -0.095
Radical nephrectomy, n 142 (43.6) 303 (38.8)
Partial nephrectomy, n 184 (56.4) 477 (61.2)
Surgical approach < 0.001
Laparoscopic, n 32 (9.8) 157 (20.1)
Hand-assisted laparoscopic, n 5 (1.5) 31 (4.0)
Robot-assisted, n 53 (16.3) 83 (10.6)
Open, n 236 (72.4) 509 (65.3) 0.159
Operation time, per hour 3.0 (2.0, 3.0) 2.0 (2.0, 3.0) < 0.001
Operation time, min 150 (110, 204) 130 (100, 170) < 0.001 0.324
Renal ischemic time, min b (n=629) 28.0 (18.9, 36.5) 23.0 (16.9, 29.0) < 0.001
Ischemia type b (n=661) 0.324
Cold ischemia 12 (3.7) 22 (2.8)
Warm ischemia 163 (50.2) 427 (54.8)
Anesthesia technique 0.141 -0.096
Inhalation agent, n 280 (85.9) 696 (89.2)
Total intravenous agent, n 46 (14.1) 84 (10.8)
Vasopressor use, n c 60 (18.4) 105 (13.5) 0.044 0.127
pRBC transfusion, n 78 (23.9) 50 (6.4) < 0.001
pRBC, unit 0 (0, 0) 0 (0, 0) < 0.001 0.224
Estimated blood loss, ml (n=1103) 450 (300, 750) 150 (90, 250) < 0.001 Crystalloid administration, ml
(n=1096) 1300 (900, 2000) 1050 (800, 1500) < 0.001
Hartmann solution, (n=1101) 299 (91.7) 719 (92.2) 0.891
Balanced solution, (n=1101) 168 (51.5) 287 (36.8) < 0.001
0.9% Normal saline, (n=1101) 104 (31.9) 134 (17.2) < 0.001 0.315
The values are presented as the median (interquartile range) or number (%).
Differences in the medians (25% and 75% percentiles) were compared between the two groups by the Mann-Whitney U test, and differences in the proportions were compared by the chi-square test or Fisher's exact test according to their expected count.
The number of patients in parenthesis for each covariate denotes the number of patients without missing values. Absence of the number of patients for any covariate means that there is no missing values for the variable.
a Liver disease include viral or alcoholic hepatitis or liver cirrhosis.
b These values are for only partial nephrectomy.
c Vasopressor included ephedrine, phenylephrine, norepinephrine, dopamine, or epinephrine.
d These values were calculated only for the variables used in the propensity score matching.
HES = hydroxyethyl starch, ASA = American society of Anesthesiologist, CKD = chronic kidney disease, ECOG performance status = Eastern Cooperative Oncology Group
performance status, eGFR = estimated glomerular filtration rate, pRBC = packed red blood cell.
Supplemental Table S2. Multivariable Cox proportional hazard regression analysis to predict new-onset chronic kidney disease stage 3a or higher or all-cause mortality during 60 months after nephrectomy as a primary outcome (n = 629).
Variable Hazard ratio (95% CI) P-value
6% hydroxyethyl starch use 1.06 (0.84 – 1.43) 0.264
Age, years 1.04 (1.02 – 1.06) < 0.001
Female 0.64 (0.39 – 0.96) 0.061
Body-mass index, kg/m2 1.00 (0.93 – 1.08) 0.866
Current smoker 0.99 (0.54 – 1.84) 0.754
Hypertension 1.30 (0.90 – 1.96) 0.251
Diabetes mellitus 1.29 (0.82 – 1.99) 0.354
Cerebrovascular accident 1.31 (0.60 – 3.02) 0.485
Ischemic heart disease 0.86 (0.24 – 3.05) 0.748
Hepatitis or liver cirrhosis 0.35 (0.09 – 1.38) 0.451
Hyperlipidemia 0.40 (0.15 – 1.44) 0.354
Preoperative proteinuria 0.65 (0.22 – 1.56) 0.745
Preoperative hemoglobin, g/dL 0.84 (0.74 – 0.95) 0.010
Preoperative albumin, g/dL 0.96 (0.65 – 1.42) 0.684
Preoperative serum creatinine, mg/dL 1.97 (1.62 – 2.43) < 0.001
Open nephrectomy 2.20 (1.24 – 4.25) 0.012
Radical vs. partial nephrectomy 1.06 (0.97 – 1.22) 0.098
Open vs. laparoscopic nephrectomy 1.11 (0.92 – 1.35) 0.110
Operation time, hour 1.25 (0.99 – 1.65) 0.079
Inhalational vs. total intravenous anesthesia 1.16 (0.65 – 2.03) 0.754
Vasopressor use a 1.02 (0.58 – 1.74) 0.966
New-onset chronic kidney disease was when estimated glomerular filtration rate decreased below 60 mL/min/1.73m2 or initiation of chronic hemodialysis or proteinuria > 500 mg/day for more than three months.
a Vasopressor included ephedrine, phenylephrine, norepinephrine, dopamine, or epinephrine.
CI = confidence interval. Harrell’s concordance index= 0.65, Gronnesby and Borgan test:
χ2=1.66, P=0.643.
Supplemental Table S3. Comparison of baseline characteristics and perioperative parameters between patients with and without hydroxyethyl starch during surgery after inverse probability of treatment weighting.
Characteristics HES group
(n=1111) Non-HES group
(n=1105) P-value Standardized difference Demographic data
Age, years 56 (46-67) 57 (49-66) 0.111 -0.008
Female, n 322 (29.0) 323 (29.2) 0.898 -0.001
Body-mass index, kg/m² 24.4 (22.6-26.5) 24.5 (22.6-26.5) 0.816 0.001
Current smoker, n 158 (14.2) 165 (14.9) 0.635 -0.012
Background medical status
ASA class III or IV 68 (6.1) 70 (6.3) 0.835 -0.001
Hypertension, n 471 (42.4) 477 (43.2) 0.713 -0.010
Diabetes mellitus, n 177 (15.9) 182 (16.5) 0.731 -0.009
Cerebrovascular accident, n 27 (2.4) 30 (2.7) 0.675 -0.009
Liver disease, n 45 (4.1) 45 (4.1) 0.979 0.001
Ischemic heart disease, n 15 (1.4) 18 (1.6) 0.590 -0.012
Hyperlipidemia, n 100 (9.0) 105 (9.5) 0.694 -0.019
Preoperative proteinuria, n 87 (7.8) 90 (8.1) 0.790 -0.003
Preoperative hemoglobin, g/dL 13.7 (12.4-14.8) 13.8 (12.5-14.9) 0.574 -0.013 Preoperative albumin, g/dL 4.4 (4.1-4.6) 4.4 (4.1-4.6) 0.869 -0.002 Preoperative eGFR, mL/min/1.73m2 79.2 (67.2-92.4) 80.1 (69.6-91.8) 0.415 -0.042 Clinical stage
T1a / 1b 751 (67.6)/ 146
(13.1)
752 (68.1) / 145
(13.1) 0.848 0.002
T2a / 2b 128 (11.5)/ 34
(3.1) 129 (11.7) / 34 (3.1)
T3a / 3b / 3c 18 (1.6)/ 14 (1.3)/
20 (1.9) 16(1.5)/ 13(1.2)/
13 (1.2)
N 0/1 1073 (96.6)/ 38
(3.4)
1071 (96.9)/ 34
(3.1) 0.845 -0.001
M 0/1 1074 (96.7)/ 37
(3.3) 1071 (96.9)/ 34
(3.1) 0.749 -0.001
Operation and anesthesia related Operation year,
2010/2011/2012/2013/2014
151 (13.6)/ 299 (26.9)/ 277 (24.9)/
256 (23.0)/ 129 (11.6)
156 (14.1)/ 295 (26.7)/ 276 (25.0)/
253 (22.9)/ 126 (11.4)
0.788 -0.002
Partial nephrectomy (vs. radical), n 658 (59.2) 634 (57.3) 0.364 0.028 Open nephrectomy (vs. laparoscopic), n 125 (11.3) 117 (10.6) 0.657 0.017
Operation time, min 134 (100-180) 140 (100-180) 0.151 0.029
Inhalation agent (vs. TIVA) 981 (88.3) 980 (88.7) 0.774 -0.011
Vasopressor use, n a 24 (2.2) 25 (2.3) 0.873 -0.001
pRBC, unit 0 (0-0) 0 (0-0) 0.467 0.002
The values are presented as the median (interquartile range) or number (%).
Differences in the medians (25% and 75% percentiles) were compared between the two groups by the Mann-Whitney U test, and differences in the proportions were compared by the chi-square test or Fisher's exact test according to their expected count.
aVasopressor included ephedrine, phenylephrine, norepinephrine, dopamine, and epinephrine.
ASA = American Society of Anesthesiologist physical status classification, HES = hydroxyethyl starch, pRBC = packed red blood cell, TIVA = total intravenous anesthesia.
Supplemental Table S4. Comparison of the occurrence of secondary outcomes between patients with and without hydroxyethyl starch during partial nephrectomy before and after propensity score matching.
Before propensity score matching
After propensity score matching
Outcomes HES group Non-HES
group
Odds ratio or median difference b
(98.8% CI)
P-value a HES group Non-HES group
Odds ratio or median difference b
(98.8% CI)
P-value a
Number of patients 176 453 157 157
Postoperative AKI stage, n
1.87 (1.17 – 3.00) 0.010 1.06 (0.55 – 2.05) 0.851
No AKI 142 (80.7) 401 (88.5) 136 (86.6) 137 (87.3)
AKI Stage 1 29 (16.5) 48 (10.6) 19 (12.1) 19 (12.1)
AKI Stage 2 or 3 5 (2.8) 4 (0.9) 2 (1.3) 1 (0.6)
CKD upstaging at one year, n
65 (36.9) 126 (27.8) 1.53 (1.07 – 2.20) 0.033 51 (32.5) 45 (28.7) 1.20 (0.74 – 1.94) 0.463 Major postoperative
complications c, n
8 (4.5) 16 (3.5) 1.30 (0.55 – 3.10) 0.550 6 (3.8) 8 (5.1) 0.74 (0.25 – 2.18) 0.586 Hospital length of
stay, days
5 (5, 6) 5 (5, 6) 0 (0 – 0) 0.717 5 (5, 6) 5 (5, 6) 0 (0 – 0) 0.570
The values are presented as the median (interquartile range) or number (%).
Before and after matching, the occurrence of postoperative AKI were compared between the two groups by the proportional odds logistic regression model. The occurrence of CKD upstaging at one year and major postoperative complications were compared between the two groups by the chi-square test or Fisher's exact test according to their expected counts.
a Statistical significance corrected for the secondary outcomes by the Bonferroni-correction to adjust for increased type I error by multiple testing (P < 0.05/4 = 0.0125).
b Odds ratios estimate the odds of the given outcome in HES versus non-HES for each secondary outcome.
c This includes urine leakage, postoperative ileus, wound infection, postoperative pneumonia, and retroperitoneal abscess.
HES = hydroxyethyl starch, AKI = acute kidney injury determined by KDIGO creatinine criteria, CKD = chronic kidney disease.
Supplemental Table S5. Results of ordinal logistic regression analysis for acute kidney injury as a secondary outcome and Cox proportional hazard regression analysis for new-onset chronic kidney disease stage 3a or higher or all-cause mortality during 60 months as a
primary outcome after partial nephrectomy using inverse probability of treatment weighting.
Logistic regression analysis (n = 622)
Cox regression analysis (n = 622)
Odds ratio (95% CI)P-value Hazard ratio (95% CI)P-value 6% hydroxyethyl starch use 1.07 (0.77 – 1.49) 0.698 1.17 (0.92 – 1.49) 0.212
Acute kidney injury was determined according to the KDIGO (Kidney disease improving global outcomes) criteria using the serum creatinine during postoperative seven days and was treated as an ordinal variable defined as no AKI, AKI stage 1, and 2 or 3. New-onset chronic kidney disease was when estimated glomerular filtration rate decreased below 60
mL/min/1.73m2 or initiation of chronic hemodialysis or proteinuria > 500 mg/day for more than three months.
CI = confidence interval.
Supplemental Figure 1. Flow diagram of the present study regarding the subgroup of partial nephrectomy. HES group = hydroxyethyl starch group.
Supplemental Figure 2. Covariate balance plot (left) and histograms (right) of distribution of standardized differences in the propensity score analysis between patients with and without hydroxyethyl starch during surgery in the total cohort.
Supplemental Figure 3. Covariate balance plot (left) and histograms (right) of distribution of standardized differences in the propensity scores between the patients with and without hydroxyethyl starch during surgery in the subgroup of partial nephrectomy.
Supplemental Figure 4. Kaplan-Meier survival curve analysis of new-onset stage 3a or higher chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73m2) or all-cause mortality according to the patients with and without 6% hydroxyethyl starch during surgery before (A) and after (B) propensity score matching in the subgroup of partial
nephrectomy. The results of log-rank test between the groups are shown on the figure.
Supplemental Figure 5. Kaplan-Meier survival curve analysis of new-onset stage 5 chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73m2) or all-cause
mortality according to the patients with and without 6% hydroxyethyl starch during surgery before (A) and after (B) propensity score matching in the subgroup of partial nephrectomy.
The results of log-rank test between the groups are shown on the figure.
