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Kidney Transplantation in Korean Patients With End-Stage Renal Disease Aged 65 and Older: A Single-Center Experience
Kidney Transplantation in Korean Patients With End-Stage Renal Disease Aged 65 and Older: A Single-Center Experience S.S. Kanga,b, W.Y. Parka,b, K. Jina,b, S.B. Parka,b, and S. Hana,b,* a Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea; and bKeimyung University Kidney Institute, Daegu, Korea
ABSTRACT Background. The mean age of patients starting dialysis in Korea has increased to older than 60 years and the proportion of patients aged 65 and older exceeded 40% in 2014. Although the number of elderly dialysis patients is increasing rapidly, percentages of elderly patients undergoing kidney transplantation (KT) are very low. Methods. We retrospectively reviewed the medical records of patients who underwent KT at Keimyung University Dongsan Medical Center between 1982 and 2016. Elderly patients (65 years old) were compared with the control group of patients in their early sixties (60e64 years old). Results. Among a total of 1209 KT patients, those in their early sixties totaled 34 (2.8%) and the elderly totaled only 18 (1.5%). Patient and allograft survival rate showed no significant differences between the elderly and those in their early sixties. Death with a functioning graft accounted for 50% in both groups. However, occurrences of bacterial infection and tuberculosis were higher in the elderly (P ¼ .011 and .047, respectively). In a multivariate analysis, longer duration of renal replacement therapy before KT and the occurrence of malignancy were independent risk factors for patient death (hazard ratio [HR], 1.027; P ¼ .014; HR, 31.934; P ¼ .016, respectively). Also, albuminuria at 6 months after KT was an independent risk factor for allograft loss (HR, 51.155; P ¼ .016). Conclusion. The overall survival rate of the elderly was not significantly lower than those in their early sixties. Even in the elderly, KT should not be delayed. In addition, careful surveillance for malignancy and measures to decrease the risk of infection are necessary.
A
CCORDING to the recent annual data report of United States Renal Data System (USRDS), the percentage of elderly patients (65 years old) who underwent renal replacement therapy (RRT) was 38.9% in 2013 [1]. Furthermore, the percentage of elderly patients in incident case of RRT has been steadily increasing to 48.7%. Similarly, the mean age of patients starting dialysis in Korea has increased to 60.3 years old, and the proportion of patients aged 65 and older increased to 40.7% in 2014 [2]. Among RRTs of end-stage renal disease (ESRD) patients, kidney transplantation (KT) is considered primary therapy by providing the best outcomes in patient survival and quality of life [3,4]. Although outcomes of KT in elderly patients were poorer than younger patients, they were better than those receiving dialysis treatments. Nevertheless, the proportion of elderly patients undergoing KT is very low ª 2017 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 49, 987e991 (2017)
compared with younger patients. According to USRDS data, the proportions of kidney transplant recipients (KTRs) among total elderly patients with ESRD (18.6%) and newly diagnosed elderly patients with ESRD (1.1%) were lower than those of patients aged 45 to 64 years (33.4% and 3.2%, respectively) [1]. Also, according to the 2015 Korean Network for Organ Sharing (KONOS) annual report, the proportion of elderly patients among total KTRs
This research was supported by the Keimyung University Research Grant of 2016. *Address correspondence to Seungyeup Han, MD, PhD, Department of Internal Medicine, Keimyung University School of Medicine, Keimyung University Kidney Institute, 56 Dalseong-Ro, Jung-Gu, Daegu 41931, Korea. E-mail: [email protected] 0041-1345/17 http://dx.doi.org/10.1016/j.transproceed.2017.03.060
987
988
was 5.1% in 2015, which was increased from 1.6% in 2011, but still lower than that of younger patients [5]. In the aging society, the numbers of elderly ESRD patients are increasing continuously, but the proportion of elderly patients undergoing KT is still low. Although the reason for lower rates of KT in elderly patients is not clear, strict selection criteria and lower interest in KT by elderly patients are considered to be one of the reasons [6]. In this study, we investigated the clinical features and outcomes of KT in the elderly and evaluated their adequacy. METHODS This study was approved by Institutional Review Board of Keimyung University, Korea (40525-201611-HR-118-01). We retrospectively reviewed the medical records of patients who underwent KT at Keimyung University Dongsan Medical Center between 1982 and 2016. Among a total of 1209 KTRs, 18 patients who were aged 65 or older and underwent KT for the first time were included for analysis and were compared with the control group of 34 patients in their early sixties (60e64 years old). The recipient variables included age, gender, cause of ESRD, history of diabetes mellitus, hypertension, methods and durations of RRT before KT, use of induction therapy, and maintenance therapy. In addition, donor variables included age, gender, donor type, and number of mismatched human leukocyte antigens (HLA). Complications were evaluated, including delayed graft function (DGF) and surgical and medical complications. DGF was defined as need for dialysis in the first week after KT. Finally, survival rates of allograft and patient and their risk factors were evaluated.
Statistical Analysis Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 18.0 (SPSS Inc., Chicago, Ill, United States). Continuous variables were presented as means standard deviation and categorical variables as frequencies with percentages. Continuous variables were compared using Student t test and categorical variables using chi-square or Fisher exact test. Survival rates of kidney allografts and patients were compared using the Kaplan-Meier method and the log-rank test. Independent risk factors for patient death and allograft loss were analyzed using Cox proportional hazards model. A P value < .05 was considered to be statistically significant.
RESULTS Baseline Characteristics
Among a total of 1209 KTRs, those in their early sixties were 34 (2.8%) and the elderly were only 18 (1.5%). The number of KTRs aged 60 or older excluded from analysis due to undergoing KT more than twice was 6 (0.5%). The average age was 66.9 2.4 years for the elderly (65-72 years) and 61.7 1.4 years for those in their early sixties (60-64 years). Among the elderly, 10 (55.6%) were men, 4 (22.2%) had diabetes mellitus, and 13 (72.2%) had hypertension. Glomerulonephritis was the most common cause of ESRD in both the elderly (50.0%) and those in their early sixties (55.9%). Hemodialysis was the most common RRT modality in both the elderly (94.4%) and those in their early sixties (70.6%). Although the duration of RRT before KT was shorter in the elderly (63.1 60.1 vs 73.4
KANG, PARK, JIN ET AL
53.2), there was no statistically significant difference. The proportion of deceased donors was 77.7% in the elderly and 64.7% for those in their early sixties. The average donor age was 53.9 15.0 years for the elderly (33-74 years) and 52.6 15.1 years for those in their early sixties (17-72 years). The numbers of HLA mismatches were 2.7 1.8 in the elderly and 3.7 1.7 for patients in their early sixties (P ¼ .052). Baciliximab and thymoglobulin was used as induction therapy in 77.8% and 16.7%, respectively, of the elderly patients and in 61.8% and 20.6%, respectively, of those in their early sixties. Complications After KT
Complications after KT are presented in Table 1. DGF occurred in 4 patients (22.2%) and surgical complications occurred in 1 patient (5.6%) in the elderly. There was no statistically significant difference between the elderly and those in their early sixties. Among medical complications, occurrence of bacterial infection and tuberculosis were higher in the elderly (P ¼ .011 and .047, respectively). Acute rejection occurred in 2 patients (11.1%) in the elderly and 4 patients (11.8%) in their early sixties. A total of 3 KTRs were diagnosed with malignancy. In the elderly, lung cancer occurred in 1 KTR, and, in those in their early sixties, 1 case each of lung cancer and papillary thyroid cancer occurred. Outcomes of KT in the Elderly and Those in Their Early Sixties
The median duration of follow up was 27.0 months. Patient and allograft survival rate showed no significant differences between the elderly and those in their early sixties (P ¼ .498 and .831, respectively). The 1-year and 5-year patient survival rates were 94.1 5.7% and 94.1 5.7%, respectively, Table 1. Complications After KT The Elderly (n ¼ 18)
DGF (%) Surgical Complications Urinary leakage Lymphocele Hemorrhage Urinary stricture None Medical complications Acute rejection Cardiovascular event Post-transplantation diabetes mellitus Malignancy Infection Bacterial infection Viral infection Fungal infection Tuberculosis Patient death Graft loss Death with functioning graft
Patients in Their Early Sixties (n ¼ 34)
P
4 1 1 0 0 0 17 16 2 1 6
(22.2) (5.6) (5.6) (0) (0) (0) (94.4) (88.9) (11.1) (5.6) (33.3)
4 4 0 1 2 1 30 27 4 2 12
(11.8) (11.8) (0) (2.9) (5.9) (2.9) (88.2) (79.4) (11.8) (5.9) (35.3)
.320 .470 .395
1 12 10 12 2 2 2 2 1
(5.6) (66.7) (55.6) (66.7) (11.1) (11.1) (11.1) (11.1) (5.6)
2 19 7 17 1 0 3 4 2
(5.9) (55.9) (20.6) (50.0) (2.9) (0) (8.8) (11.8) (5.9)
.962 .451 .011 .250 .229 .047 .425 .632 .687
.390 .944 .962 .888
KT IN KOREAN PATIENTS
in the elderly, and 96.9 3.1% and 96.9 3.1%, respectively, in those in their early sixties (Fig 1A). The number of patient deaths was 2 (11.1%) in the elderly and 3 (8.8%) in those in their early sixties. The major cause of patient death in both the elderly and patients in their early sixties was infection (100% and 66.7%, respectively; Table 1). The 1-year and 5-year allograft survival rates were 94.1 5.7% and 94.1 5.7%, respectively, in the elderly and 96.9 3.1% and 84.7 8.6%, respectively, in patients in their early sixties (Fig 1B). The number of allograft losses was 2 (11.1%) in the elderly and 4 (11.8%) in those in their early sixties. Death with a functioning graft accounted for 50% in both groups (Table 1). Clinical Risk Factors for Patient Death and Allograft Loss
Risk factors for patient death and allograft loss of KTRs aged 60 or older were analyzed using Cox proportional hazards model. In univariate and multivariate analysis, longer duration of RRT before KT (hazard ratio [HR], 1.027; 95% confidence interval [CI], 1.005e1.050; P ¼ .014) and the occurrence of malignancy (HR, 31.934; 95% CI, 1.924e529.986; P ¼ .016) showed significant association with increasing the risk of patient death (Table 2). Longer duration of RRT before KT (HR, 1.013; 95% CI, 1.000e1.025; P ¼ .045) and albuminuria at 6 months after KT (HR, 21.024; 95% CI, 1.295e341.420; P ¼ .032) were significant risk factors for allograft loss (Table 3). In the multivariate analysis, albuminuria at 6 months after KT (HR, 51.155; 95% CI, 2.110e1240.171; P ¼ .016) showed independent association with increasing the risk of allograft loss.
989
DISCUSSION
In the present study, we investigated the clinical features and outcomes of KT in the elderly, by comparing with patients in their early sixties who are close to elderly, but undergoing more KT. First, patient survival showed no significant differences between the elderly and those in their early sixties. The 1-year and 5-year patient survival rates of our study were 94.1% and 94.1%, respectively. The 5-year patient survival rate was higher than those of studies in the United States, which ranged from 67.2%e80.7% [3,7,8]. Some studies reported that the survival rates of KTRs and allografts in the elderly have improved due to the development of immunosuppressive drugs since the 2000s [9] and that Asian patients showed better survival rates of patients and allografts compared with American patients [3,10]. Most of the patients in this study (88.9% of elderly patients and 70.6% of those in their early sixties) underwent KT between 2011 and 2016. Second, according to Cox proportional hazard model, longer duration of RRT before KT (HR, 1.027; 95% CI, 1.005e1.050; P ¼ .014) and occurrence of malignancy (HR, 31.934; 95% CI, 1.924e529.986; P ¼ .016) were independent risk factors of patient death. Several studies have already reported that early KT shows better prognosis than RRTs of longer durations in the elderly [3,4,9,11]. Wolfe et al [3] reported that KTRs aged 60 to 74 showed reduced longterm mortality risk by 61% from 18 months after KT and increased life spans by 4 years compared with dialysis patients. And subsequent studies of KTRs aged 70 or older also showed better long-term survival benefits compared
Fig 1. Survival rates according to the age group by the Kaplan-Meier method. (A) Patient survival. (B) Kidney allograft survival.
990
KANG, PARK, JIN ET AL Table 2. Clinical Risk Factors for Patient Death in KTRs Aged Older Than 60 Years Univariate Variables
Age Male History of hypertension History of DM RRT duration Donor age Donor, female DDKT Induction, TMG Acute rejection Malignancy Infection
Multivariate
HR (95% CI)
0.986 1.741 5.838 2.325 1.017 1.015 2.332 1.735 0.032 0.738 9.222 1.804
P
(0.692e1.405) (0.230e13.180) (0.578e58.917) (0.201e26.838) (1.003e1.031) (0.954e1.081) (0.309e17.451) (0.253e11.912) (0.000e27863.166) (0.077e7.123) (1.212e70.193) (0.197e16.542)
.937 .591 .135 .499 .017 .632 .413 .575 .622 .793 .032 .602
HR (95% CI)
P
13.310 (0.604e293.341)
.101
1.027 (1.005e1.050)
.014
31.934 (1.924e529.986)
.016
Abbreviations: DM, diabetes mellitus; DDKT, deceased donor KT; TMG, thymoglobulin.
with dialysis patients [9,11]. However, it should be noted that KTRs older than 70 years had a higher mortality rate in the first years after KT compared with dialysis patients, and had improved survival benefits from 3.5 years after KT [9]. The most common and dangerous factors affecting the early mortality rate after KT are cardiovascular disease and infectious disease [6]. Because elderly patients are more vulnerable to infection, infectious diseases are reported as the leading cause of death in elderly KTRs [12]. In this study, infection was also a major cause of death. Therefore, future studies on optimal immunosuppressive therapies that minimize infectious diseases are needed. Allograft survival showed no significant differences between the elderly and those in their early sixties. The 1-year and 5-year allograft survival rates of our study were 94.1% and 94.1%, respectively. The 5-year allograft survival rate was also higher than those of studies in the United States, which ranged from 60.9%e90.7% [3,7,8]. Albuminuria 2þ at
6 months after KT (HR, 21.024; 95% CI, 1.295e341.420; P ¼ .032) was an independent risk factor for allograft loss in the Cox proportional hazard model. Other studies have reported that T-cellemediated rejection and congestive heart failure were associated with allograft failure [7]. In this study, there was no association between acute rejection and allograft loss, but longer durations of follow-up and more clinical cases are required in the future. The major cause of allograft loss in both the elderly and those in their early sixties were patient death with a functioning graft, not rejection. Other causes of allograft loss were chronic rejection in the elderly, and chronic rejection and recurrent glomerulonephritis in those in their early sixties. Also, in other studies, elderly KTRs were reported to experience fewer episodes of rejection but more cases of infection, compared with younger patients [8,13]. Therefore, it is very important to establish appropriate immunosuppressive therapy that avoids rejection and minimizes infection.
Table 3. Clinical Risk Factors for Allograft Loss in KTRs Aged Older Than 60 Years Univariate Variables
Age Male History of hypertension History of DM RRT duration No. of HLA mismatches Donor age Donor, female DDKT ECD Induction, TMG Surgical complication Acute rejection Malignancy Infection DGF Creatinine at 3 y Albuminuria 2þ (6 mo)
HR (95% CI)
0.910 1.270 1.931 0.856 1.013 1.205 0.995 0.883 1.507 2.935 31.364 2.159 1.003 3.698 1.523 1.430 13.128 21.024
Abbreviation: ECD, expanded criteria donor.
(0.650e1.273) (0.245e6.590) (0.315e11.849) (0.093e7.845) (1.000e1.025) (0.678e2.140) (0.944e1.049) (0.157e4.976) (0.268e8.478) (0.262e32.838) (0.000e0.741) (0.248e18.755) (0.114e8.787) (0.643e21.252) (0.169e13.719) (0.164e12.485) (0.806e213.930) (1.295e341.420)
Multivariate P
.582 .776 .477 .891 .045 .526 .853 .888 .641 .382 .622 .485 .998 .143 .708 .746 .071 .032
HR (95% CI)
P
1.003 (0.973e1.033)
.869
10.246 (0.862e121.806)
.065
51.155 (2.110e1240.171)
.016
KT IN KOREAN PATIENTS
Our study had several limitations. Our study was retrospective study of single center, and the numbers of registered patients were small. Another limitation was that, as mentioned already, 88.9% of patients older than 65 years and 70.6% of those in their early sixties underwent transplantation between 2011 and 2016, and the median duration of follow-up was relatively short at 27.0 months. This suggests that the elderly and those in their early sixties with ESRD are more likely to receive KT in recent days. Therefore, we hope to conduct long-term studies with more patients in the future. In conclusion, the overall survival rates of the elderly were not significantly lower than those of patients in their early sixties. The outcomes were better than the survival rates that are generally known of dialysis patients. Therefore, KT in the elderly should not be delayed, and KT can be a better option than longer durations of RRT in the elderly ERSD patients. In addition, after KT in the elderly, careful surveillance for malignancy, measures to decrease the risk of infection, and efforts to establish an optimal immunosuppressive therapy are necessary. ACKNOWLEDGMENTS This research was supported by the Keimyung University Research Grant of 2016.
REFERENCES [1] United States Renal Data System. 2015 USRDS annual data report: Epidemiology of Kidney Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2015. [2] ESRD Registry Committee, Korean Society of Nephrology. Current renal replacement therapy in Korea, Insan memorial
991 dialysis registry 2015. http://www.ksn.or.kr/rang_board/list.html? code¼sinchart_eng [accessed 20.10.16]. [3] Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999;341:1725e30. [4] Abecassis M, Bartlett ST, Collins AJ, Davis CL, Delmonico FL, Friedewald JJ, et al. Kidney transplantation as primary therapy for end-stage renal disease: a National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/KDOQITM) conference. Clin J Am Soc Nephrol 2008;3: 471e80. [5] The Korean Network for Organ Sharing (KONOS), Korea Centers for Disease Control and Prevention. 2015 KONOS Annual Report. http://www.konos.go.kr/konosis [accessed 20.10.16]. [6] Huang E, Segev DL, Rabb H. Kidney transplantation in the elderly. Semin Nephrol 2009;29:621e35. [7] Faravardeh A, Eickhoff M, Jackson S, Spong R, Kukla A, Issa N, et al. Predictors of graft failure and death in elderly kidney transplant recipients. Transplantation 2013;96:1089e96. [8] Knoll GA. Kidney transplantation in the older adult. Am J Kidney Dis 2013;61:790e7. [9] Heldal K, Hartmann A, Grootendorst DC, de Jager DJ, Leivestad T, Foss A, et al. Benefit of kidney transplantation beyond 70 years of age. Nephrol Dial Transplant 2010;25:1680e7. [10] Fan PY, Ashby VB, Fuller DS, Boulware LE, Kao A, Norman SP, et al. Access and outcomes among minority transplant patients, 1999-2008, with a focus on determinants of kidney graft survival. Am J Transplant 2010;10:1090e107. [11] Rao PS, Merion RM, Ashby VB, Port FK, Wolfe RA, Kayler LK. Renal transplantation in elderly patients older than 70 years of age: results from the Scientific Registry of Transplant Recipients. Transplantation 2007;83:1069e74. [12] Meier-Kriesche HU, Ojo AO, Hanson JA, Kaplan B. Exponentially increased risk of infectious death in older renal transplant recipients. Kidney Int 2001;59:1539e43. [13] Hod T, Goldfarb-Rumyantzev AS. Clinical issues in renal transplantation in the elderly. Clin Transplant 2015;29: 167e75.
ABSTRACT Background. The mean age of patients starting dialysis in Korea has increased to older than 60 years and the proportion of patients aged 65 and older exceeded 40% in 2014. Although the number of elderly dialysis patients is increasing rapidly, percentages of elderly patients undergoing kidney transplantation (KT) are very low. Methods. We retrospectively reviewed the medical records of patients who underwent KT at Keimyung University Dongsan Medical Center between 1982 and 2016. Elderly patients (65 years old) were compared with the control group of patients in their early sixties (60e64 years old). Results. Among a total of 1209 KT patients, those in their early sixties totaled 34 (2.8%) and the elderly totaled only 18 (1.5%). Patient and allograft survival rate showed no significant differences between the elderly and those in their early sixties. Death with a functioning graft accounted for 50% in both groups. However, occurrences of bacterial infection and tuberculosis were higher in the elderly (P ¼ .011 and .047, respectively). In a multivariate analysis, longer duration of renal replacement therapy before KT and the occurrence of malignancy were independent risk factors for patient death (hazard ratio [HR], 1.027; P ¼ .014; HR, 31.934; P ¼ .016, respectively). Also, albuminuria at 6 months after KT was an independent risk factor for allograft loss (HR, 51.155; P ¼ .016). Conclusion. The overall survival rate of the elderly was not significantly lower than those in their early sixties. Even in the elderly, KT should not be delayed. In addition, careful surveillance for malignancy and measures to decrease the risk of infection are necessary.
A
CCORDING to the recent annual data report of United States Renal Data System (USRDS), the percentage of elderly patients (65 years old) who underwent renal replacement therapy (RRT) was 38.9% in 2013 [1]. Furthermore, the percentage of elderly patients in incident case of RRT has been steadily increasing to 48.7%. Similarly, the mean age of patients starting dialysis in Korea has increased to 60.3 years old, and the proportion of patients aged 65 and older increased to 40.7% in 2014 [2]. Among RRTs of end-stage renal disease (ESRD) patients, kidney transplantation (KT) is considered primary therapy by providing the best outcomes in patient survival and quality of life [3,4]. Although outcomes of KT in elderly patients were poorer than younger patients, they were better than those receiving dialysis treatments. Nevertheless, the proportion of elderly patients undergoing KT is very low ª 2017 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 49, 987e991 (2017)
compared with younger patients. According to USRDS data, the proportions of kidney transplant recipients (KTRs) among total elderly patients with ESRD (18.6%) and newly diagnosed elderly patients with ESRD (1.1%) were lower than those of patients aged 45 to 64 years (33.4% and 3.2%, respectively) [1]. Also, according to the 2015 Korean Network for Organ Sharing (KONOS) annual report, the proportion of elderly patients among total KTRs
This research was supported by the Keimyung University Research Grant of 2016. *Address correspondence to Seungyeup Han, MD, PhD, Department of Internal Medicine, Keimyung University School of Medicine, Keimyung University Kidney Institute, 56 Dalseong-Ro, Jung-Gu, Daegu 41931, Korea. E-mail: [email protected] 0041-1345/17 http://dx.doi.org/10.1016/j.transproceed.2017.03.060
987
988
was 5.1% in 2015, which was increased from 1.6% in 2011, but still lower than that of younger patients [5]. In the aging society, the numbers of elderly ESRD patients are increasing continuously, but the proportion of elderly patients undergoing KT is still low. Although the reason for lower rates of KT in elderly patients is not clear, strict selection criteria and lower interest in KT by elderly patients are considered to be one of the reasons [6]. In this study, we investigated the clinical features and outcomes of KT in the elderly and evaluated their adequacy. METHODS This study was approved by Institutional Review Board of Keimyung University, Korea (40525-201611-HR-118-01). We retrospectively reviewed the medical records of patients who underwent KT at Keimyung University Dongsan Medical Center between 1982 and 2016. Among a total of 1209 KTRs, 18 patients who were aged 65 or older and underwent KT for the first time were included for analysis and were compared with the control group of 34 patients in their early sixties (60e64 years old). The recipient variables included age, gender, cause of ESRD, history of diabetes mellitus, hypertension, methods and durations of RRT before KT, use of induction therapy, and maintenance therapy. In addition, donor variables included age, gender, donor type, and number of mismatched human leukocyte antigens (HLA). Complications were evaluated, including delayed graft function (DGF) and surgical and medical complications. DGF was defined as need for dialysis in the first week after KT. Finally, survival rates of allograft and patient and their risk factors were evaluated.
Statistical Analysis Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 18.0 (SPSS Inc., Chicago, Ill, United States). Continuous variables were presented as means standard deviation and categorical variables as frequencies with percentages. Continuous variables were compared using Student t test and categorical variables using chi-square or Fisher exact test. Survival rates of kidney allografts and patients were compared using the Kaplan-Meier method and the log-rank test. Independent risk factors for patient death and allograft loss were analyzed using Cox proportional hazards model. A P value < .05 was considered to be statistically significant.
RESULTS Baseline Characteristics
Among a total of 1209 KTRs, those in their early sixties were 34 (2.8%) and the elderly were only 18 (1.5%). The number of KTRs aged 60 or older excluded from analysis due to undergoing KT more than twice was 6 (0.5%). The average age was 66.9 2.4 years for the elderly (65-72 years) and 61.7 1.4 years for those in their early sixties (60-64 years). Among the elderly, 10 (55.6%) were men, 4 (22.2%) had diabetes mellitus, and 13 (72.2%) had hypertension. Glomerulonephritis was the most common cause of ESRD in both the elderly (50.0%) and those in their early sixties (55.9%). Hemodialysis was the most common RRT modality in both the elderly (94.4%) and those in their early sixties (70.6%). Although the duration of RRT before KT was shorter in the elderly (63.1 60.1 vs 73.4
KANG, PARK, JIN ET AL
53.2), there was no statistically significant difference. The proportion of deceased donors was 77.7% in the elderly and 64.7% for those in their early sixties. The average donor age was 53.9 15.0 years for the elderly (33-74 years) and 52.6 15.1 years for those in their early sixties (17-72 years). The numbers of HLA mismatches were 2.7 1.8 in the elderly and 3.7 1.7 for patients in their early sixties (P ¼ .052). Baciliximab and thymoglobulin was used as induction therapy in 77.8% and 16.7%, respectively, of the elderly patients and in 61.8% and 20.6%, respectively, of those in their early sixties. Complications After KT
Complications after KT are presented in Table 1. DGF occurred in 4 patients (22.2%) and surgical complications occurred in 1 patient (5.6%) in the elderly. There was no statistically significant difference between the elderly and those in their early sixties. Among medical complications, occurrence of bacterial infection and tuberculosis were higher in the elderly (P ¼ .011 and .047, respectively). Acute rejection occurred in 2 patients (11.1%) in the elderly and 4 patients (11.8%) in their early sixties. A total of 3 KTRs were diagnosed with malignancy. In the elderly, lung cancer occurred in 1 KTR, and, in those in their early sixties, 1 case each of lung cancer and papillary thyroid cancer occurred. Outcomes of KT in the Elderly and Those in Their Early Sixties
The median duration of follow up was 27.0 months. Patient and allograft survival rate showed no significant differences between the elderly and those in their early sixties (P ¼ .498 and .831, respectively). The 1-year and 5-year patient survival rates were 94.1 5.7% and 94.1 5.7%, respectively, Table 1. Complications After KT The Elderly (n ¼ 18)
DGF (%) Surgical Complications Urinary leakage Lymphocele Hemorrhage Urinary stricture None Medical complications Acute rejection Cardiovascular event Post-transplantation diabetes mellitus Malignancy Infection Bacterial infection Viral infection Fungal infection Tuberculosis Patient death Graft loss Death with functioning graft
Patients in Their Early Sixties (n ¼ 34)
P
4 1 1 0 0 0 17 16 2 1 6
(22.2) (5.6) (5.6) (0) (0) (0) (94.4) (88.9) (11.1) (5.6) (33.3)
4 4 0 1 2 1 30 27 4 2 12
(11.8) (11.8) (0) (2.9) (5.9) (2.9) (88.2) (79.4) (11.8) (5.9) (35.3)
.320 .470 .395
1 12 10 12 2 2 2 2 1
(5.6) (66.7) (55.6) (66.7) (11.1) (11.1) (11.1) (11.1) (5.6)
2 19 7 17 1 0 3 4 2
(5.9) (55.9) (20.6) (50.0) (2.9) (0) (8.8) (11.8) (5.9)
.962 .451 .011 .250 .229 .047 .425 .632 .687
.390 .944 .962 .888
KT IN KOREAN PATIENTS
in the elderly, and 96.9 3.1% and 96.9 3.1%, respectively, in those in their early sixties (Fig 1A). The number of patient deaths was 2 (11.1%) in the elderly and 3 (8.8%) in those in their early sixties. The major cause of patient death in both the elderly and patients in their early sixties was infection (100% and 66.7%, respectively; Table 1). The 1-year and 5-year allograft survival rates were 94.1 5.7% and 94.1 5.7%, respectively, in the elderly and 96.9 3.1% and 84.7 8.6%, respectively, in patients in their early sixties (Fig 1B). The number of allograft losses was 2 (11.1%) in the elderly and 4 (11.8%) in those in their early sixties. Death with a functioning graft accounted for 50% in both groups (Table 1). Clinical Risk Factors for Patient Death and Allograft Loss
Risk factors for patient death and allograft loss of KTRs aged 60 or older were analyzed using Cox proportional hazards model. In univariate and multivariate analysis, longer duration of RRT before KT (hazard ratio [HR], 1.027; 95% confidence interval [CI], 1.005e1.050; P ¼ .014) and the occurrence of malignancy (HR, 31.934; 95% CI, 1.924e529.986; P ¼ .016) showed significant association with increasing the risk of patient death (Table 2). Longer duration of RRT before KT (HR, 1.013; 95% CI, 1.000e1.025; P ¼ .045) and albuminuria at 6 months after KT (HR, 21.024; 95% CI, 1.295e341.420; P ¼ .032) were significant risk factors for allograft loss (Table 3). In the multivariate analysis, albuminuria at 6 months after KT (HR, 51.155; 95% CI, 2.110e1240.171; P ¼ .016) showed independent association with increasing the risk of allograft loss.
989
DISCUSSION
In the present study, we investigated the clinical features and outcomes of KT in the elderly, by comparing with patients in their early sixties who are close to elderly, but undergoing more KT. First, patient survival showed no significant differences between the elderly and those in their early sixties. The 1-year and 5-year patient survival rates of our study were 94.1% and 94.1%, respectively. The 5-year patient survival rate was higher than those of studies in the United States, which ranged from 67.2%e80.7% [3,7,8]. Some studies reported that the survival rates of KTRs and allografts in the elderly have improved due to the development of immunosuppressive drugs since the 2000s [9] and that Asian patients showed better survival rates of patients and allografts compared with American patients [3,10]. Most of the patients in this study (88.9% of elderly patients and 70.6% of those in their early sixties) underwent KT between 2011 and 2016. Second, according to Cox proportional hazard model, longer duration of RRT before KT (HR, 1.027; 95% CI, 1.005e1.050; P ¼ .014) and occurrence of malignancy (HR, 31.934; 95% CI, 1.924e529.986; P ¼ .016) were independent risk factors of patient death. Several studies have already reported that early KT shows better prognosis than RRTs of longer durations in the elderly [3,4,9,11]. Wolfe et al [3] reported that KTRs aged 60 to 74 showed reduced longterm mortality risk by 61% from 18 months after KT and increased life spans by 4 years compared with dialysis patients. And subsequent studies of KTRs aged 70 or older also showed better long-term survival benefits compared
Fig 1. Survival rates according to the age group by the Kaplan-Meier method. (A) Patient survival. (B) Kidney allograft survival.
990
KANG, PARK, JIN ET AL Table 2. Clinical Risk Factors for Patient Death in KTRs Aged Older Than 60 Years Univariate Variables
Age Male History of hypertension History of DM RRT duration Donor age Donor, female DDKT Induction, TMG Acute rejection Malignancy Infection
Multivariate
HR (95% CI)
0.986 1.741 5.838 2.325 1.017 1.015 2.332 1.735 0.032 0.738 9.222 1.804
P
(0.692e1.405) (0.230e13.180) (0.578e58.917) (0.201e26.838) (1.003e1.031) (0.954e1.081) (0.309e17.451) (0.253e11.912) (0.000e27863.166) (0.077e7.123) (1.212e70.193) (0.197e16.542)
.937 .591 .135 .499 .017 .632 .413 .575 .622 .793 .032 .602
HR (95% CI)
P
13.310 (0.604e293.341)
.101
1.027 (1.005e1.050)
.014
31.934 (1.924e529.986)
.016
Abbreviations: DM, diabetes mellitus; DDKT, deceased donor KT; TMG, thymoglobulin.
with dialysis patients [9,11]. However, it should be noted that KTRs older than 70 years had a higher mortality rate in the first years after KT compared with dialysis patients, and had improved survival benefits from 3.5 years after KT [9]. The most common and dangerous factors affecting the early mortality rate after KT are cardiovascular disease and infectious disease [6]. Because elderly patients are more vulnerable to infection, infectious diseases are reported as the leading cause of death in elderly KTRs [12]. In this study, infection was also a major cause of death. Therefore, future studies on optimal immunosuppressive therapies that minimize infectious diseases are needed. Allograft survival showed no significant differences between the elderly and those in their early sixties. The 1-year and 5-year allograft survival rates of our study were 94.1% and 94.1%, respectively. The 5-year allograft survival rate was also higher than those of studies in the United States, which ranged from 60.9%e90.7% [3,7,8]. Albuminuria 2þ at
6 months after KT (HR, 21.024; 95% CI, 1.295e341.420; P ¼ .032) was an independent risk factor for allograft loss in the Cox proportional hazard model. Other studies have reported that T-cellemediated rejection and congestive heart failure were associated with allograft failure [7]. In this study, there was no association between acute rejection and allograft loss, but longer durations of follow-up and more clinical cases are required in the future. The major cause of allograft loss in both the elderly and those in their early sixties were patient death with a functioning graft, not rejection. Other causes of allograft loss were chronic rejection in the elderly, and chronic rejection and recurrent glomerulonephritis in those in their early sixties. Also, in other studies, elderly KTRs were reported to experience fewer episodes of rejection but more cases of infection, compared with younger patients [8,13]. Therefore, it is very important to establish appropriate immunosuppressive therapy that avoids rejection and minimizes infection.
Table 3. Clinical Risk Factors for Allograft Loss in KTRs Aged Older Than 60 Years Univariate Variables
Age Male History of hypertension History of DM RRT duration No. of HLA mismatches Donor age Donor, female DDKT ECD Induction, TMG Surgical complication Acute rejection Malignancy Infection DGF Creatinine at 3 y Albuminuria 2þ (6 mo)
HR (95% CI)
0.910 1.270 1.931 0.856 1.013 1.205 0.995 0.883 1.507 2.935 31.364 2.159 1.003 3.698 1.523 1.430 13.128 21.024
Abbreviation: ECD, expanded criteria donor.
(0.650e1.273) (0.245e6.590) (0.315e11.849) (0.093e7.845) (1.000e1.025) (0.678e2.140) (0.944e1.049) (0.157e4.976) (0.268e8.478) (0.262e32.838) (0.000e0.741) (0.248e18.755) (0.114e8.787) (0.643e21.252) (0.169e13.719) (0.164e12.485) (0.806e213.930) (1.295e341.420)
Multivariate P
.582 .776 .477 .891 .045 .526 .853 .888 .641 .382 .622 .485 .998 .143 .708 .746 .071 .032
HR (95% CI)
P
1.003 (0.973e1.033)
.869
10.246 (0.862e121.806)
.065
51.155 (2.110e1240.171)
.016
KT IN KOREAN PATIENTS
Our study had several limitations. Our study was retrospective study of single center, and the numbers of registered patients were small. Another limitation was that, as mentioned already, 88.9% of patients older than 65 years and 70.6% of those in their early sixties underwent transplantation between 2011 and 2016, and the median duration of follow-up was relatively short at 27.0 months. This suggests that the elderly and those in their early sixties with ESRD are more likely to receive KT in recent days. Therefore, we hope to conduct long-term studies with more patients in the future. In conclusion, the overall survival rates of the elderly were not significantly lower than those of patients in their early sixties. The outcomes were better than the survival rates that are generally known of dialysis patients. Therefore, KT in the elderly should not be delayed, and KT can be a better option than longer durations of RRT in the elderly ERSD patients. In addition, after KT in the elderly, careful surveillance for malignancy, measures to decrease the risk of infection, and efforts to establish an optimal immunosuppressive therapy are necessary. ACKNOWLEDGMENTS This research was supported by the Keimyung University Research Grant of 2016.
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