Archives of Medical Research 45 (2014) 188e194
ORIGINAL ARTICLE
Long-term Outcomes of Dialysis Patients After Coronary Revascularization: A Population-based Cohort Study in Taiwan Chu-lin Chou,a,* Tsung-cheng Hsieh,a,* Chih-hsien Wang,b Tsung-hsing Hung,c,d Yu-hsien Lai,b Yi-ya Chen,b Yu-li Lin,b Chiu-huang Kuo,b Ya-ju Wu,e and Te-chao Fanga,b,d a Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan Division of Nephrology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan c Division of Gastroenterology, Department of Medicine, Buddhist Dalin Tzu Chi Hospital, Chiayi, Taiwan d School of Medicine, Tzu Chi University, Hualien, Taiwan e Division of General Medicine, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan b
Received for publication September 25, 2013; accepted January 27, 2014 (ARCMED-D-13-00527).
Background and Aims. The outcomes of Chinese patients undergoing dialysis after coronary revascularization are unknown. We examined the outcomes of Taiwanese dialysis patients after coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA), or coronary stenting. Methods. Using data from the National Health Research Institute database, we determined the outcomes of 1,287 dialysis patients who underwent initial coronary revascularization between 1997 and 2008. Results. The 7-year overall survival rates were 69 4%, 68 3%, and 57 2% for the CABG, stent, and PTCA patients ( p 5 0.001), respectively. After demographic and comorbidity adjustment, hazard ratios (HRs) for all-cause death in the CABG (vs. PTCA) and stent (vs. PTCA) patients were 0.695 ( p 5 0.015) and 0.721 ( p 5 0.009). Additionally, no significant difference in all-cause death was found between the CABG and stent patients. Moreover, the $65-year-old CABG group patients and the !65-year-old coronary stent group patients showed better survival than the PTCA group patients. Compared with the PTCA and CABG groups, the coronary stent group was significantly associated with a higher risk for recurrent acute myocardial infarction (AMI). Based on age stratification, the $65-year-old stent group had a higher risk for recurrent AMI than the PTCA group (HR, 1.562; p 5 0.026). Conclusions. Chinese patients undergoing dialysis who underwent CABG or coronary stenting had better survival than those who underwent PTCA. Moreover, being $65 years old, CABG shows better survival compared with PTCA; being !65 years old, coronary stenting show better survival compared with PTCA. Ó 2014 IMSS. Published by Elsevier Inc. Key Words: Coronary artery bypass grafting, Dialysis, Percutaneous transluminal coronary angioplasty, Stent.
*
These authors contributed equally to this paper. Address reprint requests to: Te-chao Fang, M.D., Ph.D., Division of Nephrology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, No. 707, Section 3, Chung Yang Road, Hualien 97004, Taiwan; Phone: þ886-3-8561825 ext. 2253; FAX: þ886-3-8564673; E-mail: [email protected]
Introduction Coronary artery disease (CAD) in patients with end-stage renal disease (ESRD) has contributed to an increased mortality, especially derived from the deterioration of acute myocardial infarction (AMI) (1e3). The development of
0188-4409/$ - see front matter. Copyright Ó 2014 IMSS. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.arcmed.2014.01.009
Coronary Artery Disease in Dialysis Patients
ESRD deteriorates the outcomes of patients with CAD, and the pathophysiological mechanism and the course of CAD are altered in patients with ESRD, for example, in cases of advanced atherosclerosis superimposed with arterial calcification (4). The increasing trends of the incidence of CAD in dialysis patients may be attributed to the lack of effective prevention and treatment. As recently reported, the optimal coronary revascularization methods for dialysis patients with CAD are unclear (5). For example, some studies reported no significant difference in the mortality of dialysis patients after undergoing either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) (6e8). In contrast, other studies indicated that dialysis patients who underwent CABG had a higher survival rate than those who underwent PTCA (9e11). However, the previous studies were limited in that they had small study populations and short-term follow-up periods. Therefore, the outcomes of dialysis patients after coronary revascularization should be investigated using large cohort studies. Few current studies have examined the long-term comparative outcomes between CABG, coronary stenting, and PTCA in dialysis patients. In particular, a 3-year cohort study from the U.S. Renal Data System database reported that the relative risk (RR) for all-cause death was 0.80 in CABG (vs. PTCA) patients (95% confidence interval [CI], 0.76e0.84; p !0.0001) and 0.94 in stent (vs. PTCA) patients (95% CI, 0.88e0.99; p 5 0.03); however, patient outcomes between CABG and stenting were not comparative in this study (12). Moreover, an 8-year follow-up cohort study of dialysis patients indicated that compared with patients who underwent percutaneous coronary intervention (PCI), those who underwent CABG were associated with lower hazard ratios (HR) for all-cause death (HR, 0.87; 95% CI, 0.84e0.90) and AMI (HR, 0.88; 95% CI, 0.86e0.91) (13). Both studies indicated that CABG might be preferred over PTCA or PCI in patients undergoing maintenance dialysis. However, no further information was reported regarding the differences in long-term outcomes among the three different coronary revascularization methods for dialysis patients. In addition, no large cohort study on coronary revascularization has been conducted in a Chinese population. Taiwan has the highest incidence and prevalence of ESRD worldwide (2,14). The National Health Insurance (NHI) program has provided compulsory universal health insurance in Taiwan since 1995, and almost all Taiwanese citizens are enrolled in the program (2,15), providing the best representative sample for a large cohort study. The purpose of the present study was to examine the comparative outcomes between CABG, PTCA, and coronary stenting in Taiwanese dialysis patients, using the data from the NHI research database between 1997 and 2008.
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Materials and Methods Database The NHI research database was established by the Taiwan National Health Research Institute (NHRI). Since 1995, the NHI program has provided compulsory universal health insurance in Taiwan, and O99% of Taiwanese citizens are enrolled in the program (15). The NHRI was delegated to maintain the NHI research database for the NHI program and to provide clinical data for population-based longitudinal cohort investigations in Taiwan (http://w3.nhri.org.tw/ nhird/date_01.html). All Taiwanese patients with ESRD are qualified to undergo dialysis therapy free of charge, and all dialysis patients are enrolled in the NHI program. The NHI research database is one of the largest comprehensive databases worldwide and has been used as a source of data for broad analyses in several cohort studies (16,17) and our previous study (18). All data are encrypted by the NHRI to protect the privacy of individuals, providing information on patient background including birthday, sex, medical institutions, the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes, procedure codes, health-care costs, dates of admission and discharge, death date, and outpatient and inpatient claim data. Each patient is assigned a unique identification number to which all datasets are interlinked. Study Cohort and Patient Selection This longitudinal cohort study was performed with prior approval from the Ethics Committee and Human Subjects Institutional Review Board of the Tzu Chi Hospital, Hualien (TCH IRB No. 101e126). For this study we used the NHI research database of catastrophic illness registration, enrolling all patients with ESRD (ICD-9-CM no. 585) who began renal replacement therapy between January 1, 1997, and December 31, 2008. Patients who were undergoing dialysis therapy for O3 months were eligible in our study. Exclusion criteria included patients who underwent renal transplantation either before or after undergoing dialysis, those who were undergoing dialysis for !3 months, those who had undergone more than one method of coronary revascularization and those who had missing data on identification numbers, birthday, sex, or date of death. Patients who underwent dialysis therapy for O3 months and then subsequently accepted the coronary revascularization method were enrolled in this study. Patients were stratified into the following three groups according to the coronary revascularization method: PTCA group, stent group (including drug-eluting or bare-metal stents), and CABG group. The follow-up period in this study ranged from the time of initial dialysis to the time of the last dialysis, date of death, or December 31, 2008, whichever came first.
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Table 1. Demographic characteristics of the dialysis patients who underwent coronary revascularization
Age, years !65 65e74 $75 Sex Male Female Dialysis model HD PD Comorbidity Diabetes Hypertension Hyperlipidemia
CABG (n 5 166)
Stenting (n 5 250)
PTCA (n 5 871)
k (%)
n (%)
n (%)
108 (65.1) 48 (28.9) 10 (6.0)
134 (53.6) 74 (29.6) 42 (16.8)
467 (53.6) 271 (31.1) 133 (15.3)
109 (65.7) 57 (34.3)
141 (56.4) 109 (43.6)
481 (55.2) 390 (44.8)
161 (97.0) 5 (3.0)
244 (97.6) 6 (2.4)
855 (98.2) 16 (1.8)
126 (75.9) 137 (82.5) 64 (38.6)
195 (78.0) 212 (84.8) 106 (42.4)
641 (73.6) 712 (81.7) 303 (34.8)
p 0.010*
0.045*
0.584
0.344 0.534 0.078
CABG, coronary artery bypass grafting; HD, hemodialysis; PD, peritoneal dialysis; PTCA, percutaneous transluminal coronary angioplasty. Values given as number (percentage). *p !0.05.
Diagnostic (ICD-9-CM) and procedure codes were interlinked with patient identification numbers in the NHI research database. Survival time was calculated from the time of revascularization to the study endpoint, which was all-cause death or an AMI event. The ICD-9-CM diagnostic and procedure codes used were as follows: ESRD (585), AMI (410.X), diabetes mellitus (250.X), hypertension (401.Xe405.X), and hyperlipidemia (272.X) and CABG (36.11e36.19), PTCA (36.01, 36.02, and 36.05), and stenting (36.06), respectively.
Results Cohort Characteristics A total of 115,182 ESRD patients who were undergoing dialysis therapy for O3 months between January 1997 and December 2008 were identified. Among the 115,182 dialysis patients, 1287 underwent coronary revascularization, i.e., 166 CABG, 250 stent, and 871 PTCA patients. Follow-up times after CABG, PTCA, and coronary stenting were 67.1 32.6, 58.0 36.0, and 63.7 35.2 months, respectively. Demographic data of the dialysis patients who underwent coronary revascularization are summarized in Table 1.
Statistical Analysis Patients’ demographic data included age, sex, type of dialysis, and previous comorbid diseases, the differences between which were compared using the c2 test. Age (!65, 65e74, or $75 years) was analyzed as a categorical variable. The cumulative proportions of all-cause and AMI event-free survivals of the dialysis patients after undergoing CABG, PTCA, or stenting were calculated using the life table and Kaplan-Meier methods, respectively. The results of the analyses were expressed as mean SEM. The logrank rest was used to compare differences in cumulative survival between the different groups. A Cox proportional hazards model was used to assess the impact of independent predictors on the HRs of mortality and AMI in the dialysis patients after undergoing CABG, PTCA, or stenting adjusted by age, sex, dialysis model, and comorbidities. SAS statistical software (SAS System for Windows v. 9.1.3, SAS Institute, Cary, NC) was used to perform the statistical analysis. All statistical tests were two-sided; p !0.05 was considered statistically significant.
Mortality, Incidence of AMI Event, and Overall Survival Table 2 shows the mortality and incidence of an AMI event after coronary revascularization in dialysis patients. The mortality rate in CABG or stent group was relatively lower than in the PTCA group ( p !0.001). However, the Table 2. Mortality and the incidence of an AMI event in dialysis patients after undergoing coronary revascularization
Death AMI
CABG (n 5 166)
Stenting (n 5 250)
PTCA (n 5 871)
n (%)
n (%)
n (%)
p
52 (31.3) 41 (24.7)
80 (32.0) 91 (36.4)
374 (42.9) 234 (26.9)
!0.001* 0.007*
AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; PTCA, percutaneous transluminal coronary angioplasty. Values given as number (percentage). *p !0.05.
Coronary Artery Disease in Dialysis Patients
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was lower in dialysis patients !65 years old than in those $75 years old (HR, 0.629; p !0.001).
Table 3. Overall survival rate of dialysis patients after undergoing coronary revascularization Survival rate, % Month PTCA Stenting CABG
12 24 36 48 60 72 84 70 2 65 2 61 2 59 2 58 2 57 2 57 2 74 3 70 3 68 3 68 3 68 3 68 3 68 3 81 3 77 3 73 3 70 4 70 4 69 4 69 4
CABG, coronary artery bypass grafting; PTCA, percutaneous transluminal coronary angioplasty. Analysis using the life table method. Values are expressed as mean SEM.
incidence rate of an AMI event was higher in the stent group than in the CABG or PTCA group ( p !0.007). Table 3 summarizes overall survival rate of dialysis patients after undergoing coronary revascularization. The 7-year overall survival rates were 69 4%, 68 3%, and 57 2% in the CABG, stent, and PTCA groups, respectively. An increased incidence rate of an AMI event was observed in the stent patients; nevertheless, their overall survival rate after the stent procedure was favorable.
Overall Survival Rates of the Dialysis Patients after Undergoing Coronary Revascularization Based on Age Stratification Overall survival rate was significantly higher in either the CABG or stent group than in the PTCA group (Table 4). Moreover, no significant difference in overall survival rate was observed between the CABG and stent patients. Based on the age stratification, the !65-year-old patients who underwent coronary stenting had a higher survival rate than those who underwent PTCA (Figure 1). In contrast, the $65 year-old patients who underwent CABG had a higher survival rate than those who underwent a PTCA procedure. AMI Event-free Survival
The results of the Cox proportional hazards analysis of allcause death after coronary revascularization in the dialysis patients are summarized in Table 4. After demographic and comorbidity adjustment, HRs for all-cause death in the CABG (vs. PTCA) and stent (vs. PTCA) patients were 0.695 ( p 5 0.015) and 0.721 ( p 5 0.009), respectively. In addition, no significant difference in all-cause death was found between the CABG and stent patients ( p 5 0.906). The mortality rate after coronary revascularization
Table 5 summarizes the AMI event-free survival after coronary revascularization in the dialysis patients. The 7-year AMI event-free survival rates were 75 3%, 64 3%, and 73 2% in the CABG, stent, and PTCA groups, respectively. The risks for an AMI event after coronary revascularization in dialysis patients are presented in Table 6. The stent group had a higher risk for an AMI event than the PTCA group (HR, 1.438; p 5 0.004). Moreover, the CABG group had a lower risk for an AMI event than the stent group (HR, 0.650; p 5 0.023). Furthermore, based on the age stratification, a higher risk for an AMI event was found in the $65-year-old patients who underwent a stent procedure than in those who underwent a PTCA procedure (HR, 1.562; p 5 0.026), as shown in Figure 2.
Table 4. Cox proportional hazards model of all-cause death in dialysis patients after undergoing coronary revascularization
Discussion
Cox Proportional Hazards Analysis of All-cause Death
Factor Procedure Stenting vs. PTCA CABG vs. PTCA CABG vs. stenting Age, years !65 vs. $75 65e74 vs. $75 Sex Female vs. male Dialysis model HD vs. PD Comorbidity Diabetes Hypertension Hyperlipidemia
HR
95% CI
p
0.721 0.695 0.964
0.565e0.921 0.519e0.932 0.679e1.369
0.009* 0.015* 0.906
0.629 0.853
0.490e0.807 0.658e1.105
!0.001* 0.229
1.051
0.879e1.258
0.584
0.796
0.437e1.452
0.457
1.044 1.011 0.863
0.760e1.434 0.773e1.322 0.679e1.099
0.790 0.939 0.233
CI, confidence interval; CABG, coronary artery bypass grafting; HD, hemodialysis; HR, hazard ratio; PD, peritoneal dialysis; PTCA, percutaneous transluminal coronary angioplasty. *p !0.05.
Data from the NHI research database, one of the world’s largest databases, were analyzed in this study. We conducted the present study in Taiwan because of the lack of information concerning long-term outcomes of Chinese patients undergoing dialysis who underwent coronary revascularization. The 7-year overall survival rates were 69 4%, 68 3%, and 57 2% in the CABG, stent, and PTCA groups ( p 5 0.001 by the log-rank test). After the demographic and comorbidity adjustment, the major findings of our studies were as follows: (1) the survival outcome was superior in dialysis patients who underwent either CABG or coronary stenting compared with those who underwent PTCA; (2) based on the age stratification, the !65-year-old patients who underwent coronary stenting and those aged $65 years who underwent CABG had higher survival rates than those who underwent PTCA; and (3) compared with PTCA and CABG, coronary stenting was associated with a higher risk for an AMI event. Based on age stratification,
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Figure 1. Overall survival rates of dialysis patients after undergoing coronary revascularization based on the age stratification. (A) Age !65 years. (B) Age $65 years. HR represents the risk for all-cause death. Adjusted for sex, HD/PD, diabetes, hypertension, and hyperlipidemia. CI, confidence interval; CABG, coronary artery bypass grafting; HR, hazard ratio; HD, hemodialysis; PD, peritoneal dialysis; PTCA, percutaneous transluminal coronary angioplasty; Y, year. *p !0.05.
the $65-year-old stent group patients had a higher risk for an AMI event than PTCA group patients. Previous studies that compared the survival outcomes between dialysis patients who underwent CABG and those who underwent PTCA did not obtain conclusive results (5e12,19,20). For example, some small-scale studies demonstrated that the mortality of dialysis patients who underwent CABG and those who underwent PTCA did not significantly differ (6e8,19). However, other cohort studies indicated that dialysis patients who underwent CABG surgery had a higher survival rate than those who underwent PTCA (9e11). Furthermore, Herzog et al. (12,20) reported that dialysis patients who underwent CABG had better survival than those who underwent PTCA, based on data from the U.S. Renal Data System database. Results from a metaanalysis conducted in 2009 indicated that dialysis patients who underwent CABG surgery may have had lower longterm mortality rates than those who underwent PTCA (5). Data from our present study provide important insight on the effects of intervention procedures and age. Our findings indicate that the Chinese patients undergoing dialysis who underwent either CABG or coronary stenting had superior survival outcomes than those who underwent PTCA. Moreover, the $65-year-old patients who underwent CABG had a higher survival rate than those who underwent PTCA. In Table 5. AMI event-free survival of dialysis patients after undergoing coronary revascularization AMI event-free survival, % Month PTCA Stenting CABG
12 24 36 48 60 72 84 76 1 75 1 74 1 73 1 73 1 73 2 73 2 64 3 64 3 64 3 64 3 64 3 64 3 64 3 76 3 75 3 75 3 75 3 75 3 75 3 75 3
AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; PTCA, percutaneous transluminal coronary angioplasty. Analysis using life table method. Values are expressed as mean SEM.
contrast, the !65-year-old patients in the coronary stenting group had a higher survival rate than those in the PTCA group. Our data indicate that diabetes did not affect the survival of dialysis patients who underwent coronary revascularization although previous studies reported inconsistent results regarding the outcomes of dialysis patients with diabetes who underwent either CABG or PTCA treatment (12,19). For example, data from a large 5-year prospective cohort study of 3220 dialysis patients (24% of whom had diabetes) showed no significant differences in the effect of diabetes on survival between patients who underwent CABG and those who underwent PTCA (19). However, a 5-year retrospective analysis of data from the U.S. Renal Data System database indicated that dialysis patients with diabetes who underwent CABG surgery had lower incidence rates of all-cause death than those who underwent PTCA (RR, 0.81; 95% CI, 0.75e0.88; p !0.0001) (12). Regarding the survival outcome between dialysis patients receiving CABG and coronary stenting, our study shows that the survival outcome of coronary stenting was superior to those receiving PTCA but similar to those receiving CABG in dialysis patients, although previous studies did not obtain conclusive results (12,21e24). For example, some clinical studies reported no significant differences between dialysis patients who underwent coronary stenting and those who underwent CABG (21,22). However, a study using data from the U.S. Renal Data System database indicated that dialysis patients in the U.S. had improved survival after undergoing CABG surgery compared with those who underwent stenting (12). In addition, differences in survival rate between dialysis patients who underwent drug-eluting stents (DES) and those who underwent CABG also remain undefined because of scarce clinical studies. For instance, a retrospective review of 125 dialysis patients showed that the survival outcomes of dialysis patients who underwent CABG and those who
Coronary Artery Disease in Dialysis Patients Table 6. Cox proportional hazards model of AMI events in dialysis patients after undergoing coronary revascularization Factor Procedure Stenting vs. PTCA CABG vs. PTCA CABG vs. stenting Age, years !65 vs. $75 65e74 vs. $75 Sex Female vs. male Dialysis model HD vs. PD Comorbidity Diabetes Hypertension Hyperlipidemia Follow-up time, months
HR
95% CI
p
1.438 0.934 0.650
1.127e1.835 0.668e1.306 0.448e0.941
0.004* 0.690 0.023*
1.140 1.181
0.828e1.568 0.842e1.655
0.422 0.335
1.109
0.899e1.369
0.333
1.345
0.598e3.024
0.473
1.107 0.776 0.970 0.999
0.865e1.416 0.600e1.003 0.780e1.205 0.996e1.002
0.418 0.065 0.594 0.406
AMI, acute myocardial infarction; CI, confidence interval; CABG, coronary artery bypass grafting; HD, hemodialysis; HR, hazard ratio; PD, peritoneal dialysis; PTCA, percutaneous transluminal coronary angioplasty. *p !0.05.
underwent DES were similar (CABG group vs. DES group: the overall survival rates at 1, 3, and 5 years were 84.2, 64.7%, and 56.2 vs. 88.2%, 75.5, and 61.7%, respectively; p 5 0.202) (23). In contrast, a study of 29 patients who underwent CABG and 75 patients who underwent DES indicated that the former group had a higher 2-year survival rate than the latter group (84.0 vs. 67.6%, p 5 0.0271) (24). Moreover, concerning the effect of diabetes on patient survival, a randomized trial in 1900 dialysis patients with diabetes demonstrated that primary outcomes, including all-cause death and an AMI event, were observed more frequently in patients who underwent DES than in those who underwent CABG, with 5-year survival rates of 26.6 and 18.7%, respectively ( p 5 0.005) (25).
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Our study demonstrated that dialysis patients aged $65 years who underwent coronary stenting had a higher risk for an AMI event than those who underwent PTCA, suggesting that $65 year-old dialysis patients had advanced severity of atherosclerosis superimposed with arterial calcification, and that those who underwent coronary stenting alone had a higher risk for coronary restenosis. Most studies indicated that the CABG treatment was associated with lower incidence rates of restenosis and postoperative heart disease than PTCA (6,8) or coronary stenting (12,22e24). The use of the NHI research database, which is one of the world’s most reliable databases as has been widely reported, strengthens our results (16e18). Our study is the first to report long-term outcomes in Chinese patients undergoing dialysis who underwent coronary revascularization. However, this study has some limitations. First, information on the primary cause of ESRD in the patients enrolled in the study was not available from the NHI research database. Second, we were unable to obtain data on body mass index, smoking or alcohol habits, dialysis adequacy, types of coronary stents (drug-eluting stents or bare metal stents), and biochemical examination results. In conclusion, our findings indicate that Chinese patients undergoing dialysis who underwent either CABG or coronary stenting had better survival those who underwent PTCA. Moreover, the dialysis patients aged $65 years who underwent CABG had better survival than those who underwent PTCA; among those aged !65 years, those in the coronary stenting group had better survival than those in the PTCA group. The risk for an AMI event was higher in the $65-year-old patients who underwent coronary stenting than in those who underwent PTCA. Coronary revascularization may pose a technical challenge, but the findings of our study merit further investigation in a randomized prospective trial.
Figure 2. AMI event-free survival of dialysis patients after undergoing coronary revascularization based on the age stratification. (A) Age !65 years. (B) Age $65 years. HR represents the risk for an AMI event. Adjusted for sex, HD/PD, diabetes, hypertension, and hyperlipidemia. AMI, acute myocardial infarction; CI, confidence interval; CABG, coronary artery bypass grafting; HR, hazard ratio; HD, hemodialysis; PD, peritoneal dialysis; PTCA, percutaneous transluminal coronary angioplasty; Y, year. *p !0.05.
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Conflict of Interest The authors claim no conflict of interest. Acknowledgments We thank the Bureau of Health Promotion, Department of Health, and National Health Research Institutes for providing us access to the National Health Insurance research database. This study is based in part on data from the NHIRD, which are provided by the Bureau of NHI and Department of Health and managed by the National Health Research Institutes (registry no. 99041 or NHIRD-CF-001). The interpretations and conclusions contained herein do not represent those of the Bureau of NHI, Department of Health, or National Health Research Institutes. This study was supported by a grant (TCRD 100e56) from Tzu Chi General Hospital, Hualien, Taiwan, and will be presented at the Kidney Week of the American Society of Nephrology (Atlanta, GA, USA) held from November 5 to November 10, 2013.
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ORIGINAL ARTICLE
Long-term Outcomes of Dialysis Patients After Coronary Revascularization: A Population-based Cohort Study in Taiwan Chu-lin Chou,a,* Tsung-cheng Hsieh,a,* Chih-hsien Wang,b Tsung-hsing Hung,c,d Yu-hsien Lai,b Yi-ya Chen,b Yu-li Lin,b Chiu-huang Kuo,b Ya-ju Wu,e and Te-chao Fanga,b,d a Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan Division of Nephrology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan c Division of Gastroenterology, Department of Medicine, Buddhist Dalin Tzu Chi Hospital, Chiayi, Taiwan d School of Medicine, Tzu Chi University, Hualien, Taiwan e Division of General Medicine, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan b
Received for publication September 25, 2013; accepted January 27, 2014 (ARCMED-D-13-00527).
Background and Aims. The outcomes of Chinese patients undergoing dialysis after coronary revascularization are unknown. We examined the outcomes of Taiwanese dialysis patients after coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA), or coronary stenting. Methods. Using data from the National Health Research Institute database, we determined the outcomes of 1,287 dialysis patients who underwent initial coronary revascularization between 1997 and 2008. Results. The 7-year overall survival rates were 69 4%, 68 3%, and 57 2% for the CABG, stent, and PTCA patients ( p 5 0.001), respectively. After demographic and comorbidity adjustment, hazard ratios (HRs) for all-cause death in the CABG (vs. PTCA) and stent (vs. PTCA) patients were 0.695 ( p 5 0.015) and 0.721 ( p 5 0.009). Additionally, no significant difference in all-cause death was found between the CABG and stent patients. Moreover, the $65-year-old CABG group patients and the !65-year-old coronary stent group patients showed better survival than the PTCA group patients. Compared with the PTCA and CABG groups, the coronary stent group was significantly associated with a higher risk for recurrent acute myocardial infarction (AMI). Based on age stratification, the $65-year-old stent group had a higher risk for recurrent AMI than the PTCA group (HR, 1.562; p 5 0.026). Conclusions. Chinese patients undergoing dialysis who underwent CABG or coronary stenting had better survival than those who underwent PTCA. Moreover, being $65 years old, CABG shows better survival compared with PTCA; being !65 years old, coronary stenting show better survival compared with PTCA. Ó 2014 IMSS. Published by Elsevier Inc. Key Words: Coronary artery bypass grafting, Dialysis, Percutaneous transluminal coronary angioplasty, Stent.
*
These authors contributed equally to this paper. Address reprint requests to: Te-chao Fang, M.D., Ph.D., Division of Nephrology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, No. 707, Section 3, Chung Yang Road, Hualien 97004, Taiwan; Phone: þ886-3-8561825 ext. 2253; FAX: þ886-3-8564673; E-mail: [email protected]
Introduction Coronary artery disease (CAD) in patients with end-stage renal disease (ESRD) has contributed to an increased mortality, especially derived from the deterioration of acute myocardial infarction (AMI) (1e3). The development of
0188-4409/$ - see front matter. Copyright Ó 2014 IMSS. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.arcmed.2014.01.009
Coronary Artery Disease in Dialysis Patients
ESRD deteriorates the outcomes of patients with CAD, and the pathophysiological mechanism and the course of CAD are altered in patients with ESRD, for example, in cases of advanced atherosclerosis superimposed with arterial calcification (4). The increasing trends of the incidence of CAD in dialysis patients may be attributed to the lack of effective prevention and treatment. As recently reported, the optimal coronary revascularization methods for dialysis patients with CAD are unclear (5). For example, some studies reported no significant difference in the mortality of dialysis patients after undergoing either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) (6e8). In contrast, other studies indicated that dialysis patients who underwent CABG had a higher survival rate than those who underwent PTCA (9e11). However, the previous studies were limited in that they had small study populations and short-term follow-up periods. Therefore, the outcomes of dialysis patients after coronary revascularization should be investigated using large cohort studies. Few current studies have examined the long-term comparative outcomes between CABG, coronary stenting, and PTCA in dialysis patients. In particular, a 3-year cohort study from the U.S. Renal Data System database reported that the relative risk (RR) for all-cause death was 0.80 in CABG (vs. PTCA) patients (95% confidence interval [CI], 0.76e0.84; p !0.0001) and 0.94 in stent (vs. PTCA) patients (95% CI, 0.88e0.99; p 5 0.03); however, patient outcomes between CABG and stenting were not comparative in this study (12). Moreover, an 8-year follow-up cohort study of dialysis patients indicated that compared with patients who underwent percutaneous coronary intervention (PCI), those who underwent CABG were associated with lower hazard ratios (HR) for all-cause death (HR, 0.87; 95% CI, 0.84e0.90) and AMI (HR, 0.88; 95% CI, 0.86e0.91) (13). Both studies indicated that CABG might be preferred over PTCA or PCI in patients undergoing maintenance dialysis. However, no further information was reported regarding the differences in long-term outcomes among the three different coronary revascularization methods for dialysis patients. In addition, no large cohort study on coronary revascularization has been conducted in a Chinese population. Taiwan has the highest incidence and prevalence of ESRD worldwide (2,14). The National Health Insurance (NHI) program has provided compulsory universal health insurance in Taiwan since 1995, and almost all Taiwanese citizens are enrolled in the program (2,15), providing the best representative sample for a large cohort study. The purpose of the present study was to examine the comparative outcomes between CABG, PTCA, and coronary stenting in Taiwanese dialysis patients, using the data from the NHI research database between 1997 and 2008.
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Materials and Methods Database The NHI research database was established by the Taiwan National Health Research Institute (NHRI). Since 1995, the NHI program has provided compulsory universal health insurance in Taiwan, and O99% of Taiwanese citizens are enrolled in the program (15). The NHRI was delegated to maintain the NHI research database for the NHI program and to provide clinical data for population-based longitudinal cohort investigations in Taiwan (http://w3.nhri.org.tw/ nhird/date_01.html). All Taiwanese patients with ESRD are qualified to undergo dialysis therapy free of charge, and all dialysis patients are enrolled in the NHI program. The NHI research database is one of the largest comprehensive databases worldwide and has been used as a source of data for broad analyses in several cohort studies (16,17) and our previous study (18). All data are encrypted by the NHRI to protect the privacy of individuals, providing information on patient background including birthday, sex, medical institutions, the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes, procedure codes, health-care costs, dates of admission and discharge, death date, and outpatient and inpatient claim data. Each patient is assigned a unique identification number to which all datasets are interlinked. Study Cohort and Patient Selection This longitudinal cohort study was performed with prior approval from the Ethics Committee and Human Subjects Institutional Review Board of the Tzu Chi Hospital, Hualien (TCH IRB No. 101e126). For this study we used the NHI research database of catastrophic illness registration, enrolling all patients with ESRD (ICD-9-CM no. 585) who began renal replacement therapy between January 1, 1997, and December 31, 2008. Patients who were undergoing dialysis therapy for O3 months were eligible in our study. Exclusion criteria included patients who underwent renal transplantation either before or after undergoing dialysis, those who were undergoing dialysis for !3 months, those who had undergone more than one method of coronary revascularization and those who had missing data on identification numbers, birthday, sex, or date of death. Patients who underwent dialysis therapy for O3 months and then subsequently accepted the coronary revascularization method were enrolled in this study. Patients were stratified into the following three groups according to the coronary revascularization method: PTCA group, stent group (including drug-eluting or bare-metal stents), and CABG group. The follow-up period in this study ranged from the time of initial dialysis to the time of the last dialysis, date of death, or December 31, 2008, whichever came first.
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Table 1. Demographic characteristics of the dialysis patients who underwent coronary revascularization
Age, years !65 65e74 $75 Sex Male Female Dialysis model HD PD Comorbidity Diabetes Hypertension Hyperlipidemia
CABG (n 5 166)
Stenting (n 5 250)
PTCA (n 5 871)
k (%)
n (%)
n (%)
108 (65.1) 48 (28.9) 10 (6.0)
134 (53.6) 74 (29.6) 42 (16.8)
467 (53.6) 271 (31.1) 133 (15.3)
109 (65.7) 57 (34.3)
141 (56.4) 109 (43.6)
481 (55.2) 390 (44.8)
161 (97.0) 5 (3.0)
244 (97.6) 6 (2.4)
855 (98.2) 16 (1.8)
126 (75.9) 137 (82.5) 64 (38.6)
195 (78.0) 212 (84.8) 106 (42.4)
641 (73.6) 712 (81.7) 303 (34.8)
p 0.010*
0.045*
0.584
0.344 0.534 0.078
CABG, coronary artery bypass grafting; HD, hemodialysis; PD, peritoneal dialysis; PTCA, percutaneous transluminal coronary angioplasty. Values given as number (percentage). *p !0.05.
Diagnostic (ICD-9-CM) and procedure codes were interlinked with patient identification numbers in the NHI research database. Survival time was calculated from the time of revascularization to the study endpoint, which was all-cause death or an AMI event. The ICD-9-CM diagnostic and procedure codes used were as follows: ESRD (585), AMI (410.X), diabetes mellitus (250.X), hypertension (401.Xe405.X), and hyperlipidemia (272.X) and CABG (36.11e36.19), PTCA (36.01, 36.02, and 36.05), and stenting (36.06), respectively.
Results Cohort Characteristics A total of 115,182 ESRD patients who were undergoing dialysis therapy for O3 months between January 1997 and December 2008 were identified. Among the 115,182 dialysis patients, 1287 underwent coronary revascularization, i.e., 166 CABG, 250 stent, and 871 PTCA patients. Follow-up times after CABG, PTCA, and coronary stenting were 67.1 32.6, 58.0 36.0, and 63.7 35.2 months, respectively. Demographic data of the dialysis patients who underwent coronary revascularization are summarized in Table 1.
Statistical Analysis Patients’ demographic data included age, sex, type of dialysis, and previous comorbid diseases, the differences between which were compared using the c2 test. Age (!65, 65e74, or $75 years) was analyzed as a categorical variable. The cumulative proportions of all-cause and AMI event-free survivals of the dialysis patients after undergoing CABG, PTCA, or stenting were calculated using the life table and Kaplan-Meier methods, respectively. The results of the analyses were expressed as mean SEM. The logrank rest was used to compare differences in cumulative survival between the different groups. A Cox proportional hazards model was used to assess the impact of independent predictors on the HRs of mortality and AMI in the dialysis patients after undergoing CABG, PTCA, or stenting adjusted by age, sex, dialysis model, and comorbidities. SAS statistical software (SAS System for Windows v. 9.1.3, SAS Institute, Cary, NC) was used to perform the statistical analysis. All statistical tests were two-sided; p !0.05 was considered statistically significant.
Mortality, Incidence of AMI Event, and Overall Survival Table 2 shows the mortality and incidence of an AMI event after coronary revascularization in dialysis patients. The mortality rate in CABG or stent group was relatively lower than in the PTCA group ( p !0.001). However, the Table 2. Mortality and the incidence of an AMI event in dialysis patients after undergoing coronary revascularization
Death AMI
CABG (n 5 166)
Stenting (n 5 250)
PTCA (n 5 871)
n (%)
n (%)
n (%)
p
52 (31.3) 41 (24.7)
80 (32.0) 91 (36.4)
374 (42.9) 234 (26.9)
!0.001* 0.007*
AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; PTCA, percutaneous transluminal coronary angioplasty. Values given as number (percentage). *p !0.05.
Coronary Artery Disease in Dialysis Patients
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was lower in dialysis patients !65 years old than in those $75 years old (HR, 0.629; p !0.001).
Table 3. Overall survival rate of dialysis patients after undergoing coronary revascularization Survival rate, % Month PTCA Stenting CABG
12 24 36 48 60 72 84 70 2 65 2 61 2 59 2 58 2 57 2 57 2 74 3 70 3 68 3 68 3 68 3 68 3 68 3 81 3 77 3 73 3 70 4 70 4 69 4 69 4
CABG, coronary artery bypass grafting; PTCA, percutaneous transluminal coronary angioplasty. Analysis using the life table method. Values are expressed as mean SEM.
incidence rate of an AMI event was higher in the stent group than in the CABG or PTCA group ( p !0.007). Table 3 summarizes overall survival rate of dialysis patients after undergoing coronary revascularization. The 7-year overall survival rates were 69 4%, 68 3%, and 57 2% in the CABG, stent, and PTCA groups, respectively. An increased incidence rate of an AMI event was observed in the stent patients; nevertheless, their overall survival rate after the stent procedure was favorable.
Overall Survival Rates of the Dialysis Patients after Undergoing Coronary Revascularization Based on Age Stratification Overall survival rate was significantly higher in either the CABG or stent group than in the PTCA group (Table 4). Moreover, no significant difference in overall survival rate was observed between the CABG and stent patients. Based on the age stratification, the !65-year-old patients who underwent coronary stenting had a higher survival rate than those who underwent PTCA (Figure 1). In contrast, the $65 year-old patients who underwent CABG had a higher survival rate than those who underwent a PTCA procedure. AMI Event-free Survival
The results of the Cox proportional hazards analysis of allcause death after coronary revascularization in the dialysis patients are summarized in Table 4. After demographic and comorbidity adjustment, HRs for all-cause death in the CABG (vs. PTCA) and stent (vs. PTCA) patients were 0.695 ( p 5 0.015) and 0.721 ( p 5 0.009), respectively. In addition, no significant difference in all-cause death was found between the CABG and stent patients ( p 5 0.906). The mortality rate after coronary revascularization
Table 5 summarizes the AMI event-free survival after coronary revascularization in the dialysis patients. The 7-year AMI event-free survival rates were 75 3%, 64 3%, and 73 2% in the CABG, stent, and PTCA groups, respectively. The risks for an AMI event after coronary revascularization in dialysis patients are presented in Table 6. The stent group had a higher risk for an AMI event than the PTCA group (HR, 1.438; p 5 0.004). Moreover, the CABG group had a lower risk for an AMI event than the stent group (HR, 0.650; p 5 0.023). Furthermore, based on the age stratification, a higher risk for an AMI event was found in the $65-year-old patients who underwent a stent procedure than in those who underwent a PTCA procedure (HR, 1.562; p 5 0.026), as shown in Figure 2.
Table 4. Cox proportional hazards model of all-cause death in dialysis patients after undergoing coronary revascularization
Discussion
Cox Proportional Hazards Analysis of All-cause Death
Factor Procedure Stenting vs. PTCA CABG vs. PTCA CABG vs. stenting Age, years !65 vs. $75 65e74 vs. $75 Sex Female vs. male Dialysis model HD vs. PD Comorbidity Diabetes Hypertension Hyperlipidemia
HR
95% CI
p
0.721 0.695 0.964
0.565e0.921 0.519e0.932 0.679e1.369
0.009* 0.015* 0.906
0.629 0.853
0.490e0.807 0.658e1.105
!0.001* 0.229
1.051
0.879e1.258
0.584
0.796
0.437e1.452
0.457
1.044 1.011 0.863
0.760e1.434 0.773e1.322 0.679e1.099
0.790 0.939 0.233
CI, confidence interval; CABG, coronary artery bypass grafting; HD, hemodialysis; HR, hazard ratio; PD, peritoneal dialysis; PTCA, percutaneous transluminal coronary angioplasty. *p !0.05.
Data from the NHI research database, one of the world’s largest databases, were analyzed in this study. We conducted the present study in Taiwan because of the lack of information concerning long-term outcomes of Chinese patients undergoing dialysis who underwent coronary revascularization. The 7-year overall survival rates were 69 4%, 68 3%, and 57 2% in the CABG, stent, and PTCA groups ( p 5 0.001 by the log-rank test). After the demographic and comorbidity adjustment, the major findings of our studies were as follows: (1) the survival outcome was superior in dialysis patients who underwent either CABG or coronary stenting compared with those who underwent PTCA; (2) based on the age stratification, the !65-year-old patients who underwent coronary stenting and those aged $65 years who underwent CABG had higher survival rates than those who underwent PTCA; and (3) compared with PTCA and CABG, coronary stenting was associated with a higher risk for an AMI event. Based on age stratification,
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Figure 1. Overall survival rates of dialysis patients after undergoing coronary revascularization based on the age stratification. (A) Age !65 years. (B) Age $65 years. HR represents the risk for all-cause death. Adjusted for sex, HD/PD, diabetes, hypertension, and hyperlipidemia. CI, confidence interval; CABG, coronary artery bypass grafting; HR, hazard ratio; HD, hemodialysis; PD, peritoneal dialysis; PTCA, percutaneous transluminal coronary angioplasty; Y, year. *p !0.05.
the $65-year-old stent group patients had a higher risk for an AMI event than PTCA group patients. Previous studies that compared the survival outcomes between dialysis patients who underwent CABG and those who underwent PTCA did not obtain conclusive results (5e12,19,20). For example, some small-scale studies demonstrated that the mortality of dialysis patients who underwent CABG and those who underwent PTCA did not significantly differ (6e8,19). However, other cohort studies indicated that dialysis patients who underwent CABG surgery had a higher survival rate than those who underwent PTCA (9e11). Furthermore, Herzog et al. (12,20) reported that dialysis patients who underwent CABG had better survival than those who underwent PTCA, based on data from the U.S. Renal Data System database. Results from a metaanalysis conducted in 2009 indicated that dialysis patients who underwent CABG surgery may have had lower longterm mortality rates than those who underwent PTCA (5). Data from our present study provide important insight on the effects of intervention procedures and age. Our findings indicate that the Chinese patients undergoing dialysis who underwent either CABG or coronary stenting had superior survival outcomes than those who underwent PTCA. Moreover, the $65-year-old patients who underwent CABG had a higher survival rate than those who underwent PTCA. In Table 5. AMI event-free survival of dialysis patients after undergoing coronary revascularization AMI event-free survival, % Month PTCA Stenting CABG
12 24 36 48 60 72 84 76 1 75 1 74 1 73 1 73 1 73 2 73 2 64 3 64 3 64 3 64 3 64 3 64 3 64 3 76 3 75 3 75 3 75 3 75 3 75 3 75 3
AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; PTCA, percutaneous transluminal coronary angioplasty. Analysis using life table method. Values are expressed as mean SEM.
contrast, the !65-year-old patients in the coronary stenting group had a higher survival rate than those in the PTCA group. Our data indicate that diabetes did not affect the survival of dialysis patients who underwent coronary revascularization although previous studies reported inconsistent results regarding the outcomes of dialysis patients with diabetes who underwent either CABG or PTCA treatment (12,19). For example, data from a large 5-year prospective cohort study of 3220 dialysis patients (24% of whom had diabetes) showed no significant differences in the effect of diabetes on survival between patients who underwent CABG and those who underwent PTCA (19). However, a 5-year retrospective analysis of data from the U.S. Renal Data System database indicated that dialysis patients with diabetes who underwent CABG surgery had lower incidence rates of all-cause death than those who underwent PTCA (RR, 0.81; 95% CI, 0.75e0.88; p !0.0001) (12). Regarding the survival outcome between dialysis patients receiving CABG and coronary stenting, our study shows that the survival outcome of coronary stenting was superior to those receiving PTCA but similar to those receiving CABG in dialysis patients, although previous studies did not obtain conclusive results (12,21e24). For example, some clinical studies reported no significant differences between dialysis patients who underwent coronary stenting and those who underwent CABG (21,22). However, a study using data from the U.S. Renal Data System database indicated that dialysis patients in the U.S. had improved survival after undergoing CABG surgery compared with those who underwent stenting (12). In addition, differences in survival rate between dialysis patients who underwent drug-eluting stents (DES) and those who underwent CABG also remain undefined because of scarce clinical studies. For instance, a retrospective review of 125 dialysis patients showed that the survival outcomes of dialysis patients who underwent CABG and those who
Coronary Artery Disease in Dialysis Patients Table 6. Cox proportional hazards model of AMI events in dialysis patients after undergoing coronary revascularization Factor Procedure Stenting vs. PTCA CABG vs. PTCA CABG vs. stenting Age, years !65 vs. $75 65e74 vs. $75 Sex Female vs. male Dialysis model HD vs. PD Comorbidity Diabetes Hypertension Hyperlipidemia Follow-up time, months
HR
95% CI
p
1.438 0.934 0.650
1.127e1.835 0.668e1.306 0.448e0.941
0.004* 0.690 0.023*
1.140 1.181
0.828e1.568 0.842e1.655
0.422 0.335
1.109
0.899e1.369
0.333
1.345
0.598e3.024
0.473
1.107 0.776 0.970 0.999
0.865e1.416 0.600e1.003 0.780e1.205 0.996e1.002
0.418 0.065 0.594 0.406
AMI, acute myocardial infarction; CI, confidence interval; CABG, coronary artery bypass grafting; HD, hemodialysis; HR, hazard ratio; PD, peritoneal dialysis; PTCA, percutaneous transluminal coronary angioplasty. *p !0.05.
underwent DES were similar (CABG group vs. DES group: the overall survival rates at 1, 3, and 5 years were 84.2, 64.7%, and 56.2 vs. 88.2%, 75.5, and 61.7%, respectively; p 5 0.202) (23). In contrast, a study of 29 patients who underwent CABG and 75 patients who underwent DES indicated that the former group had a higher 2-year survival rate than the latter group (84.0 vs. 67.6%, p 5 0.0271) (24). Moreover, concerning the effect of diabetes on patient survival, a randomized trial in 1900 dialysis patients with diabetes demonstrated that primary outcomes, including all-cause death and an AMI event, were observed more frequently in patients who underwent DES than in those who underwent CABG, with 5-year survival rates of 26.6 and 18.7%, respectively ( p 5 0.005) (25).
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Our study demonstrated that dialysis patients aged $65 years who underwent coronary stenting had a higher risk for an AMI event than those who underwent PTCA, suggesting that $65 year-old dialysis patients had advanced severity of atherosclerosis superimposed with arterial calcification, and that those who underwent coronary stenting alone had a higher risk for coronary restenosis. Most studies indicated that the CABG treatment was associated with lower incidence rates of restenosis and postoperative heart disease than PTCA (6,8) or coronary stenting (12,22e24). The use of the NHI research database, which is one of the world’s most reliable databases as has been widely reported, strengthens our results (16e18). Our study is the first to report long-term outcomes in Chinese patients undergoing dialysis who underwent coronary revascularization. However, this study has some limitations. First, information on the primary cause of ESRD in the patients enrolled in the study was not available from the NHI research database. Second, we were unable to obtain data on body mass index, smoking or alcohol habits, dialysis adequacy, types of coronary stents (drug-eluting stents or bare metal stents), and biochemical examination results. In conclusion, our findings indicate that Chinese patients undergoing dialysis who underwent either CABG or coronary stenting had better survival those who underwent PTCA. Moreover, the dialysis patients aged $65 years who underwent CABG had better survival than those who underwent PTCA; among those aged !65 years, those in the coronary stenting group had better survival than those in the PTCA group. The risk for an AMI event was higher in the $65-year-old patients who underwent coronary stenting than in those who underwent PTCA. Coronary revascularization may pose a technical challenge, but the findings of our study merit further investigation in a randomized prospective trial.
Figure 2. AMI event-free survival of dialysis patients after undergoing coronary revascularization based on the age stratification. (A) Age !65 years. (B) Age $65 years. HR represents the risk for an AMI event. Adjusted for sex, HD/PD, diabetes, hypertension, and hyperlipidemia. AMI, acute myocardial infarction; CI, confidence interval; CABG, coronary artery bypass grafting; HR, hazard ratio; HD, hemodialysis; PD, peritoneal dialysis; PTCA, percutaneous transluminal coronary angioplasty; Y, year. *p !0.05.
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Conflict of Interest The authors claim no conflict of interest. Acknowledgments We thank the Bureau of Health Promotion, Department of Health, and National Health Research Institutes for providing us access to the National Health Insurance research database. This study is based in part on data from the NHIRD, which are provided by the Bureau of NHI and Department of Health and managed by the National Health Research Institutes (registry no. 99041 or NHIRD-CF-001). The interpretations and conclusions contained herein do not represent those of the Bureau of NHI, Department of Health, or National Health Research Institutes. This study was supported by a grant (TCRD 100e56) from Tzu Chi General Hospital, Hualien, Taiwan, and will be presented at the Kidney Week of the American Society of Nephrology (Atlanta, GA, USA) held from November 5 to November 10, 2013.
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