Chinese Medical Journal 2010;123(21):3079-3083
Effects of the novel 6% hydroxyethyl starch 130/0.4 on renal
function of recipients in living-related kidney transplantation
WU Yan, WU An-shi, WANG Jun, TIAN Ming, JIA Xin-yuan, RUI Yan and YUE Yun
Keywords: hydroxyethyl starch; renal function; living-related kidney transplantation
Background The optimal colloid for use during kidney transplantation is not clear. Patients undergoing living-related
kidney transplantation (LRKT) were used to compare the protective effects of 6% hydroxyethyl starch 130/0.4 (HES
130/0.4) and 4% succinylated gelatine, as donor kidney procurement, ischemia time and surgical conditions are
comparable. Stroke volume variation (SVV) was used to monitor intravascular volume to avoid renal allograft
Methods Eighty patients undergoing LRKT were divided into two groups: group H received 6% HES 130/0.4 and group
G received 4% succinylated gelatine. All donors and recipients received 15–25 ml/kg of the relevant colloid during
surgery. Arterial blood pressure (ABP), heart rate (HR), central venous pressure (CVP), SVV and cardiac index (CI),
electrocardiography (ECG) and SpO2 were monitored continuously. SVV was kept between 6%–13% and mean arterial
pressure at 100–130 mmHg. Samples of venous blood and urine were obtained 30 minutes after unclamping and on the
mornings of post-operative days (POD) 1–4 to measure serum and urine β2-microglobulin, urine α1-microglobulin,
microalbumin and N-acetyl-β-D-glucosaminidase. Blood urea nitrogen (BUN) and creatine were determined
pre-operation (t0), 3 hours after surgery (t1) and on PODs 1 (t2), 2 (t3), 4 (t4), 7 (t5) and 10 (t6). Urine output was
recorded at t1, t2, t5, t6.
Results Age, body weight, body surface area (BSA), operation time, urine output and the colloid volume infused were
comparable between the groups and hemodynamics were stable during surgery. BUN, serum creatine, serum
β2-microglobulin and urine β2-microglobulin decreased significantly after surgery in both groups relative to the baseline.
BUN decreased significantly in group H compared with group G at t1, t2 and t4. Urine microalbumin decreased
significantly in group H on POD 4 compared with group G. Urine α1-microglobulin was not significantly different between
the two groups.
Conclusion Both colloids can be safely used for LRKT, but HES130/0.4 was associated with a more rapid recovery of
Chin Med J 2010;123(21):3079-3083
within the kidney graft during renal transplantation.1–4
Intervention should be implemented to prevent DGF
before it occurs. Fluid therapy has a major influence on
the recovery of kidney allograft function, and colloids
play an important role.5,6 The optimal colloid for use in
kidney transplantation remains unknown. Hydroxyethyl
starch (HES) solutions are widely used as volume
expanders.7–11 Although there are still some debates
regarding whether HES impairs renal graft function,12,13
adverse events have only been seen in patients that
received high molecular weight and highly substituted
forms of HES (such as HES 200/0.6). Osmotic,
nephrosis-like lesions were reported in 80% of
transplanted kidneys after the use of routine volumes of
HES 200/0.6 in brain-dead donors.14 Another prospective
randomized trail comparing HES 200/0.6 and gelatin used
for volume expansion in brain-dead donors found that
HES impaired immediate restoration of renal function in
kidney transplant recipients.15
mechanism for this may be swelling and vacuolization of
the tubular cells, and tubular obstruction due to
elayed graft function (DGF) is considered to be the
result of an accumulation of various harmful factors
The most likely
hyper-viscous urine.16 Also, the slow degradation of high
molecular weight or highly substituted HES may increase
plasma osmotic pressure, leading to renal dysfunction.17
Third grade, medium-molecular-weight HES with a low
molar substitution (HES 130/0.4) has a better profile for
renal protection, but its effect on the renal allograft during
kidney transplantation is not clear. A recent retrospective
study, in which the colloid were administered only to
donors, found that, compared with gelatin, administration
of HES 130/0.4 to brain-dead donors was associated with
Department of Anesthesiology, Beijing Chaoyang Hospital, Capital
Medical University, Beijing 100020, China (Wu Y, Wu AS, Rui Y
and Yue Y)
Department of Anesthesiology, Third Hospital, Peking University,
Beijing 100083, China (Wang J)
Department of Anesthesiology, Beijing Friendship Hospital,
Capital Medical University, Beijing 100050, China (Tian M)
Basic Medical Research Center, Beijing Chaoyang Hospital,
Capital Medical University, Beijing 100020, China (Jia XY)
Correspondence to: Dr. YUE Yun, Department of Anesthesiology,
Beijing Chaoyang Hospital, Capital Medical University, Beijing
100020, China (Tel: 86-10-85231463. Email: yueyun@hotmail.
Chin Med J 2010;123(21):3079-3083
better renal function in recipients.18 However, the effects
of HES 130/0.4 (given to the recipient during surgery) on
renal function have not been investigated.
The purpose of this study was to evaluate the effects of
HES 130/0.4 on the renal function of recipients after
living-related kidney transplantation (LRKT). Either HES
130/04 or succinylated gelatin were given to both donors
and recipients. Stroke volume variation (SVV) was used
to monitor intravascular volume to avoid allograft
After approval by the Local Ethics Committee, 80
patients (and 80 donors) undergoing LRKT in Beijing
ChaoYang Hospital were recruited between June and
November 2009. All donors were healthy individuals
between 22–37 years old. Recipients were between 18–70
years old. Patients and donors were randomized into two
groups receiving either 6% HES 130/0.4 (Voluven®;
Fresenius Kabi Germany) (group H) or 4% gelatin
(Gelofusine®; B. Braun Australia) (group G). Exclusion
criteria were left ventricular ejection < 50% or receipt of
a previous graft.
Anesthesia and fluid maintenance
All patients and donors received general anesthesia.
Midazolam, sufentanil, propofol, rocuronium and
remifentanil were used for anesthesia induction and
maintenance, with isoflurane applied as necessary.
Donors received 7 ml/kg of the relevant colloid over a
30-minute period during anesthesia induction and 3
ml·kg-1·h-1 of crystalloid Ringer’s lactate solution for
maintenance. During surgery, colloid was infused at 3
ml·kg-1·h-1 until the end of the procedure. Recipient arterial
blood pressure (ABP), stroke volume variation (SVV;
Vigileo® FloTrac System; Edward LifeSciences, USA),
heart rate (HR), SpO2 and ETco2 were monitored on
arrival in the operating room (OR). Recipients received 7
ml/kg of the relevant colloid over a 30-munite period
during anesthesia induction. After tracheal intubation,
central venous pressure (CVP) was monitored through a
catheter placed in the right internal jugular sub-clavicular
vein. Crystalloid of Ringer’s lactate solution (2 ml·kg-1·h-1)
was infused for maintenance during surgery. The colloid
infusion speed was adjusted to keep SVV ≤13%. Red
blood cells were infused to keep Hbg ≥8 g/dl. Systolic ABP
was kept above 160 mmHg after unclamping. If ABP could
not be kept stable for more than 3 minutes, dopamine was
infused at 1–10 µg·kg-1·min-1.
Measurement of renal function
Blood urea nitrogen (BUN) and serum creatinine
concentrations (markers for glomerular filtration rate and
general hydration) were determined pre-operation (t0), 3
hours after surgery (t1) and on post-operative days 1
(POD 1) (t2), POD 2 (t3), POD 4 (t4), POD 7 (t5) and
POD 10 (t6). Urine output was recorded at t1–6. Urine
alpha 1-microglobulin (α1-MG), beta 2-microglobulin
N-acetyl-β-D-glucosaminidase (NAG) and serum β2-MG
levels were used as specific markers of glomerular and
tubular injury,19 and were measured 30 minutes after
unclamping, and on the morning of POD 1, POD 2, and
POD 4. Samples of venous blood and urine were stored at
–70°C for later batch analysis. These samples were
measured using enzyme linked immunosorbent assays
(ELISA; Rapidbio, USA), along with an automated
ELISA reader (MULTISKAN MK3, Thermo, USA) and a
spectrophotometer (UNICO, UV-2000, Shanghai, China).
Sample size estimation was based on renal function
concentrations between the groups of up to 50 μmol/L
were regarded as clinically irrelevant. According to our
previous work, the post-operative SDs for serum
creatinine were 66 μmol/L and 62 μmol/L; representative
of at least 68 patients (34 in each group). Each
donor:recipient pair was assigned a randomized number
generated from a random number table. The investigator
received a set of envelopes containing information
regarding the colloid identified by the random numbers.
The envelope was opened when the patient arrived in the
OR. Data were analyzed using SPSS v.11.5 software
(SPSS Inc., Chicago, IL, USA). Normally distributed data
are presented as mean ± SD and intergroup analysis was
carried out using an independent-t test for comparison of
the means. Qualitative data were analyzed using the χ2
test. A P value <0.05 was considered to be significant.
Donor demographic characteristics and the volumes of
the relevant colloid and crystalloid fluids administered
during surgery were similar. The warm ischemic times for
all the allografts were within 3 minutes of each other and
cold ischemic time within 1 hour (Table 1).
Table 1. Donor’s demographics, operation time and fluid infusion
Items Group G (n=39)
Age (years) 22±3
Body weight (kg) 63±7
Duration of OP (minutes) 103±23
Colloid volume (ml) 1018±76
Crystalloid volume (ml) 756±107
Recipient demographics and operative details
Two patients (1 in each group) required further surgery
due to anastomotic bleeding on POD 3 or POD 4.
Another patient died from acute massive hemorrhage due
to vessel rupture on POD 4. All other recipients fully
recovered. Thus, 77 recipients (39 from group G and 38
from group H) met the criteria and were enrolled in the
in serum creatinine
Group H (n=38)
Chinese Medical Journal 2010;123(21):3079-3083
study. The demographics, pre-operative ejection fraction
(EF) values, the volume of the relevant colloid and
crystalloid fluids administered during surgery, the
duration of surgery, and length of postoperative hospital
was not significantly different between the two groups
(Table 2). Intra-operative hemodynamic parameters, such
as systolic ABP and CI, and volume control parameters
including SVV and CVP were also similar between the
two groups (Table 3).
Table 2. Recipient’s demographics, pre-operation and
intra-operation data base
Body weight (kg)
Preoperative Hgb (g/L)
Duration of OP (minures)
Dopamine infusion (case)
Intra-OP colloid volume (ml)
Intra-OP crystalloid volume (ml)
Intra-OP urine output (ml)
Intra-OP RBC infused (ml)
Postoperative hospital stay (days)
BSA: body surface area. OP: operation.
Recipient urine output, BUN and serum creatinine
There were no significant differences in urine output
between the two groups during or after surgery; however,
the urine output of group H on POD 1 (t2) was greater
than that of group G (12 062 ml vs. 10 725 ml) (Table 4).
BUN and serum creatinine baseline levels were similar in
both groups. After surgery, BUN was decreased
significantly in group H compared with group G on POD
1 (P=0.024), POD 2 (P=0.012) and POD 4 (P=0.021).
Serum creatinine decreased significantly in both groups
post-operatively, but was not significantly different
between the groups (Table 4).
Glomerular and tubular injury markers
All specific markers of glomerular and tubular injury,
such as urine mALB levels, serum and urine β2-MG
levels, urine 1-MG, and NAG levels, were not
significantly different between the two groups (Table 5);
however, urine mALB levels at t4 were significantly
lower in group H.
In this study, we compared the effects of two colloids,
gelatin and HES 130/0.4, on the renal function of LRKT
recipients. The two groups were comparable in terms of
the donors’ physical status, the kidney allograft ischemic
time and the recipients’ pre-anesthetic evaluations.
As we know, maintaining an adequate intravascular
volume is even more important than the type of perfusion
fluid itself for good perfusion of the kidney.16,20,21 Using
Group G (n=39)
Group H (n=38)
the intravascular volume parameter, SVV, we could adjust
the rate of fluid administration to make sure that the
patient maintained an optimal intravascular volume
situation.22,23 Both colloids are widely used in major
surgery for plasma volume expansion. Gelatin has no
adverse effects on renal function and is normally used as
a standard for volume substitution.24 However, the
pharmacological properties of hydroxyethyl starch
solutions have constantly improved over the last decade.
For example, the latest HES generation, HES 130/0.4, has
a total body clearance about 23–31 times faster than that
of the first generation hetastarch, and exhibits the best
risk/benefit ratio of all available HES.25 However, there is
still some debates surrounding the effects of hetastarch
solutions on renal function, especially in the field of
kidney transplantation. These solutions have seldom been
used in previous studies comparing the effects of colloids
used in major surgery for volume expansion on
subclinical markers of renal function.
A limitation of these studies was that glomerular and
tubular injury was not clear. In a recent study, using
urinary 1-MG and urinary IgG:creatinine as the markers
of glomerular and tubular dysfunction, Mahmood and
co-workers25 compared the effects of two kinds of HES
(weight 200/0.62 and 130/0.4) and gelatin on renal
function during aortic aneurysm surgery. They found that,
when HES infusion was accompanied by double the
volume of crystalloid, renal function improved compared
with that after gelatin infusion.26 Blasco and colleagues18
compared the effects of HES 130/0.4 and HES 200/0.6
infusion into brain-dead donors on renal function after
transplantation. They reported significantly lower rates of
DGF and decreased serum creatinine levels in the HES
130/0.4 group compared with the HES 200/0.6 group.18
The limitation of the study is that they only administered
colloid to the donors and there was a lack of the
intra-operative data from the recipients. Both of these
authors suggested that further studies should be
undertaken, especially in
In the present study, BUN levels in group H decreased
significantly compared with those in group G on POD 1
(P=0.024), POD 2 (P=0.012) and POD 4 (P=0.021). This
indicated a relatively rapid recovery of renal function in
group H, although kidney function in both groups
recovered well. Both serum and urine β2-MG levels
decreased in both of groups, indicating that tubular
function also recovered well. Urine mALB levels in
group H were significantly lower on POD 4 compared
with group G, suggesting a more rapid recovery of
glomerular filtration. Explanations for these differences
mainly include improved hemorheology and reduced
whole blood viscosity, as well as a reduction in renal
capillary leakage in group H.26 Smaller molecules of
starch reduce erythrocyte aggregation, so improved
hemorheology is achieved by administering HES
130/0.4.28,29 There was no obvious increase in urine
the field of renal
Chin Med J 2010;123(21):3079-3083
Table 3. Comparison of intra-operative heamodynamics and Hbg between the two groups during surgery
G (n=39) 176±26 171±25 191±18
H (n=38) 181±31 172±29 193±16
G (n=39) 10±3 7±3
H (n=38) 10±2 7±2
G (n=39) 9±3 9±3
H (n=38) 10±2 10±3
G (n=39) 4.4±0.8 4.5±0.9 5.6±1.0
H (n=38) 4.7±0.8 4.5±0.6 5.5±0.5
G (n=39) – 10.5±2.2 10.8±2.0
H (n=38) – 10.4±2.4 9.9±2.0
Items Groups Before incision
Before 3-min after
End of OP
Table 4. Changes of routine renal function, BUN, serum Cr and urine output of recipients between the two groups after surgery
G (n=39) 16.1±4.8 9.3±3.3 BUN (mmol/L)
H (n=38) 16.7±4.6 7.0±3.7*
G (n=39) 728±213 337±108 Cr (μmol/L)
H (n=38) 719±217 311±149
Urine output (ml) G (n=39) – 10 725±3739
H (n=38) – 12 062±2549
*P <0.05, compared to group G.
Table 5. Changes of kidney unit injury bio-protein markers of recipients between the two groups after surgery
Items Groups 30-min after unclamping
G (n=39) 21±5.1 Serum β2-MG (mg/L)
H (n=38) 19.6±5.8
G (n=39) 23.8±3.9 Urine β2-MG (mg/L)
H (n=38) 21.4±6.8
G (n=39) 42.0±16.6 Urine α1-MG (mg/L)
H (n=38) 40.5±14.9
Urine mALB (mg/L) G (n=39) 94.8±38.9
H (n=38) 104.4±39.6
*P <0.05, compared to group G.
1-MG and NAG levels, or other biological protein
indicators, suggesting that there was no allograft kidney
There are several limitations in this study. With regard to
protein indicators of glomerular and tubular injury, more
post-operative time-points could be sampled so that more
developmental trends in the recovery of the kidney units
are obtained. Moreover, long-term follow-up will be done
in our next study, which might provide more
comprehensive evidence regarding kidney function after
In conclusion, the present results suggest that
third-generation rapidly degradable, low substitution
(HES 130/0.4) is associated with slightly better renal
function compared with gelatin. However, further studies
Acknowledgements: The authors thank Dr. WANG Wei and Dr.
YIN Hang for their help to the study.
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Edited by CHEN Li-min