The waiting time for deceased-donor kidney-only transplantations in Japan is long. Herein, we assessed the effect of length of dialysis on the outcomes of these patients.
We divided patients into 2 groups based on length of dialysis (Group A, <15 years, and Group B, ≥15 years), and compared the background and outcomes after kidney transplantation.
Group A included 210 patients and Group B included 35 patients. In Group B, 20% of transplants were from living donors. Patient age (P = .017) and the hepatitis C infection rate (P = .018) were significantly higher in Group B, whereas hypertension (P = .011), diabetes (P = .041), and ABO-incompatibility rates (P = .015) were significantly higher in Group A. The 5- and 10-year survival rates were 97.0% and 95.4%, respectively, in Group A and 97.1% and 97.1%, respectively, in Group B. The 5- and 10-year graft survival rates were 95.4% and 84.8%, respectively, in Group A and 97.1% and 73.1%, respectively, in Group B. There were no significant differences between the groups in patient survival (P = .74) and graft survival (P = .72). The 5- and 10-year cardiovascular event-free survival rates were 95.9% and 92.4%, respectively, in Group A and 88.6% and 76.8%, respectively, in Group B. Cardiovascular event-free survival was significantly higher in Group A (P = .038). Cox stepwise multivariate analysis indicated that length of dialysis was a significant predictor of cardiovascular events (hazard risk, 1.007; range, 1.001–1.012; P = .012).
The prognosis after kidney transplantation is promising even after a long length of dialysis, although evaluation of the cardiovascular risk is needed in these cases.
A revised organ transplantation law was introduced in Japan on July 17, 2010. Prior to its introduction, organ transplantation from brain-dead donors was permitted only when the potential donor had previously agreed to the donation under such circumstances and when the potential donor's family assented to organ donation. At present, the organs of deceased individuals whose intentions regarding organ donation are unknown can be donated after consent is obtained from the families; as a result, the number of brain-dead organ donations has increased five-fold. Among the increased number of brain-dead donated organs, donated kidneys are reportedly preferentially provided to patients undergoing pancreas-kidney transplantation. Accordingly, the number of kidney-only donations has decreased from 175 in 2009 to 101 in 2014 . The mean waiting time until kidney transplantation was 15.6 years in 2010 . Based on data from the Japanese registry for renal replacement therapy, the cumulative 10-year survival rate was 36.0%, 15-year survival rate was 22.8%, and 20-year survival rate was 15.8% after dialysis for patients who began dialysis after 1983. In the present study, we aimed to assess the characteristics and outcomes of kidney transplantation in patients at our institute after a long or short period of dialysis.
In the present study, we compared patient backgrounds and prognosis between 2 groups of patients undergoing kidney transplantation: Group A with a length of dialysis of <15 years and Group B with a length of dialysis of ≥15 years. In Japan, recipients of deceased donor kidney transplants are chosen by the Japan Organ Transplant Network according to their guidelines. Thus, the opportunity for receiving donations from deceased donor kidney is equal among institutions in Japan. Therefore, we believe that our cohort of patients who received deceased kidney donations represented the Japanese population of kidney failure patients awaiting kidney transplantation.
The rate of diabetes was 12.4% in Group A and 0% in Group B. In Japan, the rate of diabetes as the original disease in recipients of donor kidneys is small. In 2009, 1 year before the revised organ transplantation law was introduced, there were 10 diabetic patients of a total 171 patients who underwent deceased donor kidney transplantation (5.8%) and 159 diabetic patients of a total 1041 patients who underwent living-donor kidney transplantation (15.3%) . Thus, the 12.4% of diabetic patients in our cohort are similar to the proportion of all Japanese recipients. The prognosis of diabetic dialysis patients is poor. Ningyan et al reported that patients with diabetes experienced cardiovascular events that resulted in their removal from the transplantation wait list with a median time of 8.16 years . Cardiovascular disease is the most common cause of death in diabetic patients, accounting for more than one half of cases . According to these disease backgrounds, the opportunity to become a recipient candidate was small in diabetic patients with a long length of dialysis.
The mean body mass index (BMI) of our cohort was 20.1 kg/m2. There was no difference between Group A and Group B. According to previous research, the mean BMI of dialysis patients was 21.5 kg/m2 in 2012 and 20.7 kg/m2 in 2001 . Our cohort included patients from October 1990 to March 2014. The low mean BMI might have been influenced by patients who underwent transplantation in the 1990s and 2000s. In fact, the mean BMI from 2010 to 2014 in our cohort was 20.9 ± 3.9 kg/m2.
Four patients in Group B received kidneys from living donors; the reason for their long duration on dialysis before kidney transplantation, from living donors, was their lack of knowledge regarding kidney transplantation as a treatment for end-stage renal disease. In a survey among patients with end-stage renal disease on the adequacy of information provided on renal replacement therapies, an “excellent and good” status was reported in 80.8% for information provided on hemodialysis, 49.8% for information provided on peritoneal dialysis, and 32.5% for information provided on kidney transplantation . The number of new dialysis patients was 38,055, and kidney transplantation was performed in only 1610 patients in 2012 . It is the duty of the physician to explain the 3 types of renal replacement therapies to patients with end-stage renal disease.
It is unclear whether long-term dialysis is related to graft or patient survival. Kimura et al and Kohei et al  demonstrated that the outcomes of kidney transplantation in long-term dialysis patients were similar to those in short-term dialysis patients. In contrast, Cosio et al concluded that an increased time on dialysis prior to kidney transplantation was associated with decreased survival in transplant recipients. In our cohort, there were no significant differences in patient or graft survival between groups. However, the cardiovascular event-free survival rate was superior in Group A. Cox stepwise multivariate analysis, which included all variables with a P value of <.05 on univariate analysis, indicated that length of dialysis was a significant predictor of cardiovascular events. Meier-Kriesche et al  compared the rate of cardiac death in kidney transplantation patients according to length since transplantation with that of patients on the waiting list for donor kidneys according to length on the waiting list. The cardiovascular disease rates peaked during the first 3 months following transplantation and decreased subsequently according to time since transplantation. In contrast, the cardiovascular disease rates among patients on the transplantation waiting list increased sharply and progressively according to the length of time on the waiting list. Their data suggest that the development or progression of atherosclerosis and cardiovascular disease could be ameliorated by the restoration of renal function with a transplant. In Japan, the 5 major causes of death in dialysis patients are heart failure (27.2%), infection (20.4%), malignancy (9.1%), cerebrovascular disease (7.5%), and acute myocardial infarction (4.5%) . Total cardiovascular disease accounts for 39.2% of these causes of death. On the other hand, the 5 major causes of death among transplant recipients were infection (20.2%), heart disease (11.8%), malignancy (15.1%), cerebrovascular disease (10.0 %), and intestinal disease (8.6%). Total cardiovascular disease accounts for 21.8% of these causes of death . The rate of cardiovascular disease was higher in dialysis patients than in transplant recipients. These epidemiological results also support the higher risk of cardiovascular disease in dialysis patients.
Testing for coronary artery disease includes noninvasive measures, such as myocardial perfusion studies, dobutamine stress echocardiography, or assessment of biomarker levels. The American Society of Transplantation recommends that high-risk patients undergo a cardiac stress test . The risk factors for determining patients at high-risk include a prior history of coronary artery disease, age of >45 years for men or >55 years for women, coronary artery disease in a first-degree relative, current cigarette smoking status, diabetes, hypertension, fasting total cholesterol >200 mg/dL, high-density lipoprotein cholesterol <35 mg/dL, and left ventricular hypertrophy . In patients with a long length of dialysis or in those who have at least 1 risk factor, noninvasive tests are required.
This study has certain limitations. First, it was a single-center study. Second, precise lipid data were lacking until 1997, and, therefore, we could not evaluate the relationships between cardiovascular events and lipid levels.
In conclusion, there were no significant differences in patient survival or graft survival according to dialysis vintage. Patients with a length of dialysis of ≥15 years prior to transplantation had an inferior cardiovascular event-free survival rate compared with patients with a short length of dialysis, and their rate of hepatitis C virus infection was also high. It is important for physicians to provide appropriate information concerning renal replacement therapy, including kidney transplantation, to patients with end-stage renal disease. For patients with a long length of dialysis, evaluation of cardiovascular risk is necessary. Further studies are required to fully evaluate the risks associated with transplantation in patients with a long length of dialysis.