Ann Transplant, 2012; 17(2): 5-10 Special Report

Received: 2011.11.29
Accepted: 2012.02.10 Cost analysis of living donor kidney transplantation in
Published: 2012.06.29
China: A single-center experience
Authors Contribution: Wenyu ZhaoABCDEF, Lei ZhangBC, Shu HanBC, Youhua ZhuD, Liming WangD,
A Study Design
B Data Collection
Meisheng ZhouF, Li ZengADG
C Statistical Analysis
D Data Interpretation
Organ Transplantation Institute of PLA, Changzheng Hospital, Second Military Medical University, Shanghai,
E Manuscript Preparation
P.R. China
F Literature Search
G Funds Collection
Source of support: This study was fully supported and funded by the Natural Science Foundation of China
(No.81000310).

Summary
Background: Kidney transplantation is the most cost-effective option for the treatment of end-stage
renal disease, but the financial aspects of kidney transplantation have not yet been
fully investigated. The purpose of this study was to determine the hospital cost of
living donor kidney transplantation in China and to identify factors associated with
the high cost.
Material/Methods: Demographic and clinical data of 103 consecutive patients who underwent living do-
nor kidney transplantation from January 2007 to January 2011 at our center were re-
viewed, and detailed hospital cost of initial admission for kidney transplantation was
analyzed. A stepwise multiple regression analysis was computed to determine predic-
tors affecting the total hospital cost.
Results: The median total hospital cost was US $10,531, of which 69.2% was for medications,
13.2% for surgical procedures, 11.4% for para clinics, 3.7% for accommodations,
0.5% for nursing care, and 2.0% for other miscellaneous medical services. A multi-
variate stepwise logistic regression model for overall cost of transplantation revealed
that the length of hospital stay, induction therapy, steroid-resistant rejection, main-
tenance therapy, infection status and body weight were independent predictors af-
fecting the total hospitalization cost.
Conclusions: Although the cost of living donor kidney transplantation in China is much lower
than that in developed countries, it is a heavy burden for both the government and
the patients. As medications formed the greater proportion of the total hospitaliza-
tion cost, efforts to reduce the cost of drugs should be addressed.

Key words: living donor kidney transplantation hospital cost financial analysis

Full-text PDF: http://www.annalsoftransplantation.com/fulltxt.php?ICID=883217

Word count: 2209
Tables: 3
Figures:
References: 13
Authors address: Li Zeng, Organ Transplantation Institute of PLA, Changzheng Hospital, Second Military Medical University,
No. 415 Fengyang Road, Huangpu District, Shanghai, 200003, P.R. China, e-mail: zengli111109@yahoo.com.cn
or zwyisy@yahoo.com.cn

5
Special Report
Background
Kidney transplantation is now threatened by the
global shortage of transplantable kidneys. In
China, patients and transplant surgeons are in-
creasingly dependent on living kidney donors.
Although living donor kidney transplantation of-
fers many benefits, it is a costly procedure [1],
especially in China, where health care systems
face greater economic pressures due to financial
constraints. The financial resource shortage cri-
sis has challenged many Chinese transplant cent-
ers to control costs and resource utilization asso-
ciated with kidney transplantation.
However, no published report on the costs of
living donor kidney transplantation in China is
available at present, and factors associated with
higher medical expenses in living donor kidney
transplantation remain unknown. Therefore, we
undertook a cost identification analysis to deter-
mine the overall direct cost for living donor kid-
ney transplantation and factors that are associat-
ed with higher costs at a single organ transplant
center in China.
Material and Methods
Between January 2007 and January 2011, 103 liv-
ing-related donor kidney transplantations were
performed at the Organ Transplantation Institute
of Changzheng Hospital in Shanghai. The de-
tailed medical and financial data of all recipients
were retrospectively reviewed. The demographic
data including sex, age, body weight of the recip-
ients, waiting time and panel-reactive antibody
(PRA), immunosuppressive therapy data includ-
ing induction therapy and maintenance therapy,
length of hospital stay (LOS) and specific post-
operative complications including delayed graft
function (DGF) requiring dialysis, biopsy-prov-
en acute rejection and infections treated by an-
tibiotics were recorded. The immunosuppressive
protocol during the induction period consist-
ed of the classical association of methylpredni-
solone with or without a lymphocyte-depleting
agent (rabbit anti-human thymocyte globulin,
rATG) depending on evolution of the patients.
Maintenance therapy consisted of a calcineu-
rin inhibitor (cyclosporine or tacrolimus), my-
cophenolate mofetil (MMF) and prednisolone.
In our center, methylprednisolone pulse therapy
was used for the initial treatment of acute rejec-
tion. When a steroid-resistant rejection failed to
respond to methylprednisolone, a lymphocyte-
depleting agent was used.
6
Ann Transplant, 2012; 17(2): 5-10
In the present study, hospital costs included all
the medical charges during the primary hospi-
talization for transplantation, consisting of ac-
commodations (wards and diet), medications,
surgical procedures, para clinics including lab-
oratory and imaging examinations, nursing and
other miscellaneous medical costs, but not in-
direct costs such as those related to productivi-
ty loss due to days off work. Since the hospital-
ization costs were recorded in different years,
they had to be adjusted in terms of the inflation
rate. Taking 2010 as adjustment reference, the
costs recorded across years from 2006 to 2009
were inflated to those in 2010 assuming an an-
nual inflation rate of 4%. To be internationally
comparable, the cost data calculated based on
Chinese Yuan (CNY ) were converted to US
dollars (US $) using an exchange rate of US $1
= CNY 6.8 according to the purchasing pow-
er parities of 2010 reported by the Organization
for Economic Cooperation and Development.
Statistical analysis
To identify perioperative factors associated with
a higher cost in living donor kidney transplanta-
tion, 3 patient variables (sex, age and body weight),
and 6 postoperative variables (LOS, induction
therapy protocol, maintenance therapy protocol,
DGF, acute rejection and infection) were analyzed.
According to the above variables, the patients were
divided into 3 groups: male versus female; induc-
tion therapy with a lymphocyte-depleting agent
versus no induction therapy; and tacrolimus-based
versus cyclosporine-based maintenance therapy.
They were also classified by age into 3 categories
(<45 years, 45 to 60 years and >60 years), by body
weight into 3 categories (<50 kg, 50 to 70 kg and
>70 kg), and by LOS into 3 categories (<30 days,
30 to 60 days and >60 days). In addition, patients
were compared on the basis of the presence or ab-
sence of DGF, acute rejection (steroid-sensitive re-
jection or steroid-resistant rejection) and infection.
Since the financial data were not normally dis-
tributed, a log transformation was performed.
The transformed data were normally distribut-
ed, and therefore all comparisons for the total
hospitalization costs between groups were per-
formed with independent Students t test or 1-way
ANOVA, as appropriate. Differences were con-
sidered to be significant for P<0.05. Continuous
variables with normal distribution were expressed
as mean SD, while continuous variables with
non-normal distribution were expressed as me-
dian (interquartile range, IR).
Ann Transplant, 2012; 17(2): 5-10
A stepwise multiple regression analysis was com-
puted to determine the predictors of total hos-
pital cost. A stepwise selection method was used
to fit the model. For a variable to be included in
the multiple regression analysis, its F statistic on
univariate analysis had to be significant at the
P<0.10 level. The criterion for retention of a varia-
ble in the model was P<0.05. With this technique,
each variable included in the final model made
a unique contribution to the total cost. Mallows
C (p) criterion was used to prevent over-fitting
data. SPSS 17.0 for Windows (SPSS Inc. Chicago,
Illinois, USA) was used for all statistical analyses.
Results
Demographic characteristics of the recipients
Of the 103 recipients selected, 81 (78.6%) were
male and 22 (21.4%) were female, with a mean
age of (34.017.3) years and a mean weight of
(63.29.6) kg. The median waiting time for kidney
transplants was 8 months (IR, 6m). All recipients
had a PRA <10%. The median hospital stay dur-
ing primary hospitalization was 37 days (IR, 21d).
During the induction period, 24 patients were treat-
ed with methylprednisolone alone, and the remain-
ing 79 patients received methylprednisolone with
a lymphocyte-depleting agent (rATG). For main-
tenance therapy, 52 patients were treated with a
cyclosporine-based immunosuppressive regimen,
and the remaining 51 patients received a tacroli-
mus-based immunosuppressive regimen. DGF de-
veloped in 3 (2.9%) patients, and acute rejection
episodes (ARE) in 16 (15.5%) patients, of which
10 patients were reversed by pulse steroids, and the
other 6 patients were treated with rATG. Infectious
complications occurred in 13 (12.6%) patients.
Hospital costs
The median cost subsets and contribution of
each to the total hospitalization cost are shown in
Table 1. The median total hospitalization cost for
living donor kidney transplantation was $10,531
(IR, $3,368), of which 69.2% was for medica-
tions, 13.2% for surgical procedures, 11.4% for
para clinics, 3.7% for accommodation, 0.5% for
nursing care, and 2.0% for other miscellaneous
medical services.
Factors influencing hospitalization costs
The results of comparisons for the total hospi-
talization costs between groups are shown in
Zhao W et al Cost of living kidney transplantation in China
Table 1. Costs of first hospitalization.
Cost sub-sets Median (IR) ($) Total cost (%)
Accommodations 370 (163) 3.7
Medications 7,582 (3,046) 69.2
Surgical procedures 1,448 (76) 13.2
Para clinics 1,159 (541) 11.4
Nursing care 57 (22) 0.5
Other miscellaneous
134 (65) 2.0
costs
Total 10,531 (3,368) 100.0
Table 2. The female patients had a higher total
cost than the male patients, which was also as-
sociated with increased LOS, high body weight,
use of rATG-based induction therapy and tacroli-
mus-based maintenance therapy. The total cost
was also higher in patients with DGF, acute rejec-
tion and infection. There was no significant cor-
relation between age and the total cost.
To determine the cause of higher cost in the fe-
male patients, we also evaluated differences in
demographic characteristics between the males
and females patients (data not shown). Females
were lighter (54.99.8 vs. 65.110.5 kg, P<0.05),
but had a longer LOS (43 vs. 35 days, P<0.05)
and a higher incidence of steroid-resistant re-
jection (9.1% vs. 4.9%, P>0.05) and infection
(18.2% vs. 11.1%, P>0.05) than males.
Table 3 is a summary of the stepwise multiple
regression model. LOS, the induction therapy
protocol, steroid-resistant rejection, the main-
tenance therapy protocol, infection and body
weight were identified as independent predic-
tors for total hospitalization cost.
Discussion
Although kidney transplantation is unquestiona-
bly the preferred therapy for most patients with
ESRD [2], the high cost poses a heavy burden
on both governments and patients [3], especial-
ly in developing countries [4,5]. In China, trans-
plant centers are increasingly under pressure to
identify major determinants of costs and ways
of controlling them. To determine whether it is
possible to save on the cost and explore ways to
achieve cost reduction, detailed analyses of clin-
ical and financial data are required.
7
Special Report Ann Transplant, 2012; 17(2): 5-10

Table 2. Comparisons for the total hospitalization costs between groups.

Variables n Total costs ($)* t (or F) P

Sex
Male 81 10,433 (4,225)
2.023 0.044
Female 22 10,712 (5,264)
Age
<45 years 68 10,421 (4,386)
4560 years 29 10,697 (4,774) 1.896 0.152
>60 years 6 11,167 (3,587)
Body weight
<50 kg 14 10,749 (6,006)
5070 kg 67 10,368 (3,808) 5.097 0.007
>70 kg 22 12,123 (4,639)
Length of hospital stay
<30 d 26 8,815 (2,867)
3060 d 64 10,672 (3,741) 119.87 0.000
>60 d 13 19,467 (9,172)
Induction therapy
No 24 8,807 (3,783)
7.283 0.000
Yes 79 11,498 (4,354)
Maintenance therapy
Cyclosporine 52 10,315 (3,500)
5.452 0.000
Tacrolimus 51 12,749 (4,953)
DGF
No 100 10,442 (4,037)
4.343 0.000
Yes 3 14,270 (7,894)
Acute rejection
No 87 10,098 (3,678)
Steroid-sensitive rejection 10 12,734 (4,917) 28.56 0.000
Steroid-resistant rejection 6 15,195 (7,717)
Infection
No 90 10,199 (3,941)
6.678 0.000
Yes 13 13,624 (9,969)
* Data presented as median (interquartile range).

As demonstrated in our study, the median cost for
primary hospitalization for living donor kidney
transplantation is $10,531, which is much lower
than that in developed countries, such as 15,380
in Germany [6], 14,100 in France [7], and $47,462
in the United States [8]. The cost is also lower
than that of deceased donor kidney transplanta-
tion ($11,389) in our center. As the data show, the
greater proportion (69.2%) of this cost is related
to medications, especially immunosuppressive reg-
imens. This proportion of cost is out of the health
care systems control and is significantly influenced
by international drug prices. The cost from surgical
procedures accounts for 13.2% of the total cost and
is relatively fixed. In kidney transplantation, there
are other significant variables that influence the
total cost, such as accommodations, nursing care
and para clinics, which are dependent on LOS.

8
Ann Transplant, 2012; 17(2): 5-10
Table 3. Comparisons for the total hospitalization costs between groups.
Variables
Constant 10.379
LOS 0.010
Induction therapy protocol 0.263
Steroid-resistant rejection 0.265
Maintenance therapy
0.125
protocol
Infection 0.117
Body weight 0.003
By using a stepwise multiple regression mod-
el, we determined predictors influencing the
cost of living donor kidney transplantation in a
Chinese transplant center. We found that LOS,
induction therapy protocol, steroid-resistant re-
jection, maintenance therapy protocol, infec-
tion and body weight were independent predic-
tors influencing the total hospital cost. LOS was
shown by the stepwise multiple regression mod-
el to be a more important factor than the other
variables that influence the total cost. This is be-
cause LOS in our cohort was much longer than
that in the United States (37 days vs. 6.1 days [8]).
One possible reason for the longer hospital stay
in China is the difference in the health care sys-
tems. In China, only developed urban areas have
qualified hospitals to perform kidney transplan-
tation and provide medical care services for kid-
ney recipients. Like most organ transplant cent-
ers in China, most patients in our center come
from undeveloped rural areas of China, where
the local hospitals and clinics are unable to pro-
vide sufficient medical care services for them,
such as drug concentration monitoring and dos-
ing adjustment. As a result, long-term care servic-
es for kidney transplant recipients in China are
usually provided by the same hospitals that per-
formed the kidney transplantation.
Induction therapy and steroid-resistant rejection
were also shown as independent predictors of cost
when the use of lymphocyte-depleting agents was
taken into account. In our center, the cost of a
typical (50 mg/day) 7-day rATG-based induction
therapy is $4,735, which is expensive for average
Chinese patients. However, the relationship be-
tween use of a lymphocyte-depleting agent and
total cost is complex. The use of antilymphocyte
induction therapy significantly reduces the inci-
dence of acute rejection, especially in patients
Zhao W et al Cost of living kidney transplantation in China
SE Model R2 P
0.064 0.000
0.001 0.481 0.000
0.022 0.581 0.000
0.039 0.636 0.000
0.021 0.673 0.000
0.030 0.689 0.000
0.001 0.696 0.002
at high immunologic risk [9]. However, induc-
tion agents in patients at low immunologic risk
are thought to be associated with an increased
risk of infection and higher hospital cost [10].
Thus, we may be faced with deciding which pa-
tients will benefit from antilymphocyte induction
therapy. This question deserves careful analysis.
Maintenance therapy, infection and body weight
were also independent predictors of increased
cost, and are mainly related to drug prices. As the
acquisition cost of tacrolimus in China is higher,
the total cost was also higher among patients who
received tacrolimus compared to patients who re-
ceived cyclosporine. The effect of LOS and the
cost of antibiotics accounted for the higher total
cost of patients with infection. For body weight,
we speculated that patients with higher body
weight tended to need higher doses of immuno-
suppressive drugs, resulting in higher total cost.
DGF and steroid-sensitive rejection were also as-
sociated with higher cost in our center because
of increased LOS, during which dialysis support
was required. However, when both variables were
examined in the multiple regression analysis,
they were not independent predictors of the to-
tal cost, possibly because no special expensive
drugs were used for the treatment of DGF and
steroid-sensitive rejection in our center. Similarly,
sex and age were not significant factors influenc-
ing the total cost.
A number of strategies seem justified and might
lead to cost savings in living donor kidney trans-
plantation. Our study suggests that shortening the
average length of hospital stay would decrease the
hospital cost for most patients. However, a clos-
er scrutiny of this strategy may reveal that it pro-
vides only illusory savings due to the pattern of
9
Special Report
medical care in China, where the length of hos-
pital stay is closely related to the resumption of
kidney function. These discharged patients soon
shift the costs of rejection, dialysis or infection to
the outpatient setting, without truly reducing the
total cost. Reducing the cost of drugs seems to be
an optimal strategy to reduce the hospital cost.
We suggest the following strategies to reduce the
cost of drugs: (1) Limiting use of lymphocyte-de-
pleting agents for induction in patients at high-
risk for acute rejection lymphocyte-depleting
agents are the backbone for induction therapy
in China at present, and their high cost poses a
heavy financial burden on patients. But as lym-
phocyte-depleting agents reduce acute rejection
and graft failure in high-immunological-risk pa-
tients, its use in these patients may be cost-effec-
tive [11]. (2) Using nondihydropyridine CCB or
ketoconazole to minimize the CNI dose use of
cytochrome P-450 inhibitors such as diltiazem and
ketoconazole may lower the dose of CNI with-
out affecting the therapeutic blood level, thus
reducing the cost [12,13]. (3) Using adequate-
ly tested bioequivalent generic drugs except
for tacrolimus and mTORi, cyclosporine, MMF
and azathioprine are all available as generics in
China. The efficacy and safety of these generics
have been firmly established by the State Food
and Drug Administration of China.
Conclusions
10. Hardinger KL, Rasu RS, Skelton R et al: Thy-
In conclusion, our study provides comprehen-
sive cost information for living donor kidney
transplantation in China, and identifies the ma-
jor determinants affecting total hospital costs in
living donor kidney transplantation. Last but not
the least, it is noteworthy that this study was per-
formed in a single center, and generalizing the
results to a wider level must be done with care.
Multicenter studies should be performed to con-
firm the results.
References:
1. Niakas D, Kontodimopoulos N: Is renal trans-
plantation the most cost-effective and prefer-
able therapy for patients suffering from end-
stage renal disease or not? Health Policy, 2009;
89: 32931
10
Ann Transplant, 2012; 17(2): 5-10
2. Wolfe RA, Ashby VB, Milford EL et al: Compar-
ison of mortality in all patients on dialysis, pa-
tients on dialysis awaiting transplantation, and
recipients of a first cadaveric transplant. N Engl
J Med, 1999; 341: 172530
3. Evans RW, Kitzmann DJ: An economic analysis
of kidney transplantation. Surg Clin North Am,
1998; 78: 14974
4. Nourbala MH, Einollahi B, Kardavani B et al:
The cost of kidney transplantation in Iran. Trans-
plant Proc, 2007; 39: 92729
5. Elsharif ME, Elsharif EG, Gadour WH: Costs of
hemodialysis and kidney transplantation in Su-
dan: a single center experience. Iran J Kidney
Dis, 2010; 4: 28284
6. Hagenmeyer EG, Hussler B, Hempel E et al:
Resource use and treatment costs after kidney
transplantation: impact of demographic factors,
comorbidities, and complications. Transplanta-
tion, 2004; 77: 154550
7. Chaumard N, Fagnoni P, Nerich V et al: Hospi-
tal costs of renal transplant management. Trans-
plant Proc, 2008; 40: 344044
8. Saidi RF, Elias N, Kawai T et al: Outcome of kid-
ney transplantation using expanded criteria do-
nors and donation after cardiac death kidneys:
realities and costs. Am J Transplant, 2007; 7:
276974
9. Gaber AO, Knight RJ, Patel S et al: A Review of
the Evidence for Use of Thymoglobulin Induc-
tion in Renal Transplantation. Transplant Proc,
2010; 42: 1395400
moglobulin induction dosing strategies in a low-
risk kidney transplant population: three or four
days? J Transplant, 2010; 2010: 957549
11. Schenker P, Ozturk A, Vonend O et al: Single-
dose thymoglobulin induction in living-donor
renal transplantation. Ann Transplant, 2011;
16: 5058
12. Patton PR, Brunson ME, Pfaff WW et al: A pre-
liminary report of diltiazem and ketoconazole.
Their cyclosporine-sparing effect and impact
on transplant outcome. Transplantation, 1994;
57: 88992
13. Gerntholtz T, Pascoe MD, Botha JF et al: The
use of a cyclosporin-ketoconazole combination:
Making renal transplantation affordable in de-
veloping countries. Eur J Clin Pharmacol, 2004;
60: 14348