NDT Advance Access originally published online on May 9, 2008
Nephrology Dialysis Transplantation 2008 23(8):2447-2450; doi:10.1093/ndt/gfn232
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End-stage renal disease (ESRD) and its treatment in Japan
Division of Nephrology and Kidney Center, Shuwa General Hospital, Kasukabe-shi, Japan
Correspondence and offprint requests to: Yusuke Tsukamoto, Division of Nephrology and Kidney Center, Shuwa General Hospital, 1200 Yaharashinden, Kasukabe-shi, Japan. E-mail: tsukamoto{at}jinzou.net
Keywords: BMI; CKD; dialysis; end-stage renal disease; transplant
In Japan, mandatory urine testing to detect kidney diseases and diabetes has been carried out for industrial workers (since 1972), school children (since 1973) and citizens over 40 years of age (since 1982) [1]. Despite these efforts, the prevalence of dialysis patients in Japan reached 264 473 (2069.9 per million) by the end of 2006 [2]. The increase in prevalence is no more exponential than the increase seen uptil 1995, but it has not yet reached its plateau phase. Why is the prevalence of ESRD per population the highest in Japan compared to all other nations (USRDS database: http://www.usrds.org/)? Japan is also known for having very few kidney transplants compared to the prevalence of ESRD. Not only is the total number of transplants low, but living donation is also the predominant choice for kidney transplantation (939 out of 1136 in 2007), which strongly differs from the rest of the world (Figure 1; http://www.asas.or.jp/jst/report_top.html).
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Dialysis therapy in Japan |
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 Top Dialysis therapy in Japan Kidney transplant in JapanReferences |
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Figure 1 shows a change in the incidence of dialysis patients in Japan. The percentage of diabetes (DM) as a primary cause of ESRD has largely overtaken chronic glomerulonephritis (CGN) since 1998. The incidence of dialysis patients due to CGN has actually started to decline since 1996. On the other hand, ESRD due to diabetes and nephrosclerosis (NS) still continues to rise [2]. According to the National Survey of Diabetes in 2002 (only available in Japanese, http://www1.mhlw.go.jp/toukei/tounyou/), 7.4 million Japanese adults (>20 y/o) were estimated to suffer from diabetes (HgbA1C>6.1%) and this number reflects 9.0% of the general Japanese population (127 million in 2002). If this included ‘possible’ diabetes (HgbA1C: 5.8–6.1%), the estimated total population of diabetes would be 16.2 million. This survey also demonstrated that the prevalence of diabetes is rapidly increasing because it was only 1.37 million according to the 1997 survey. However, the awareness of diabetic patients has not improved much between 1997 and 2002. Only half of the patients continued to receive treatment even after they were diagnosed by their voluntary health check-up and only 10% were estimated to be under treatment if they were incidentally diagnosed. In diabetic patients under treatment, at least 15.2% were estimated to suffer from CKD. Thus, at least 617 000 diabetic patients would have been candidates for ESRD in 2002 and this increase in the number of diabetic patients can explain the continuous rise in incidence of ESRD in Japan.
Another unique phenomenon in Japan is a continuous rise in the incidence of ESRD in males (64% in 2006), while the incidence has almost reached a plateau in female patients [3]. The percentage of males in both incidence (64% in 2006) and prevalence (61% by the end of 2006) of ESRD is much higher than that in the USA (55.5% and 55.8%, respectively) (http://www.usrds.org/). Why has ESRD increased in males? A Japanese government survey indicated that the BMI of the general male population over 70 years of age rapidly increased from 14.0 to 25.5%, while it remained almost stable in women (24.6–26.7%). According to the study by the Japanese Society of Nephrology (JSN), a higher BMI enhanced the odds ratio of ESRD, especially in males, but not in females [4]. According to the Task Force of the CKD initiative by the JSN, the average GFR in the Japanese general population was lower than in the USA [5]. If a GFR was <50 ml/min by the age of 50 years, there would be a greater chance of developing ESRD by the age of 89 years in males. Such an ethnic difference in kidney function in the general population and the longer general life expectancy may also explain the higher prevalence of ESRD in Japan.
The lower mortality rate of dialysis patients also prevents suppression of the prevalence of ESRD in Japan compared to other nations. The crude mortality rate of dialysis patients has risen from 7.9 to 9.7% since 1983 and remained almost steady during the past 10 years (9.2% in 2006). The 1-, 10- and 20-year crude survival rate was 86.7%, 36.1% and 20.0% by 31 December 2006, respectively [2]. Although the rapid increase in the incidence of ESRD is mainly due to diabetes and hypertension as a primary cause and the rising average age at the initiation of dialysis therapy (64 y/o in 2006), the general survival rate of dialysis patients has declined. According to the DOPPS study, the relative risk of mortality (adjusted) was 2.84 in Europe and 3.78 in the USA (if Japan is 1.0) [6]. The better survival rate in Japan can partly be explained by a lower incidence of cardiovascular comorbidity at the time of initiation of dialysis therapy and probably better care of the patients during maintenance dialysis [7,8]. The DOPPS study gives a unique opportunity to compare practices among nations. According to this study, better care may not be explained by doses of erythropoiesis stimulating agents (ESA) nor urea kinetics, but by the number of minutes doctors spend with their patients [9]. This might be true if we compare the outcome with the USA only (because European countries usually have longer contact times than Japan). The ‘better’ care of dialysis patients may be based on, at least to some extent, the almost unlimited availability of dialysis therapy due to a good reimbursement system in Japan.
However, the most important factor to affect the difference in mortality rate among nations may be a difference in the incidence of cardiovascular events in dialysis patients as well as in the general population. In fact, cardiovascular comorbidity is far more prominent in the USA than in Japan. The WHO database clearly shows that despite a high incidence of hypertension and diabetes (http://www.who.int/whosis/mort/download/en/index.html), cardiovascular mortality is much lower in Asian countries, including Japan.
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Kidney transplant in Japan |
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TopDialysis therapy in JapanKidney transplant in JapanReferences |
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Since the Law Concerning Human Organ Transplants was enforced in Japan in 1997, only 45 heart transplants inside Japan (80 heart transplants abroad) and 82 kidney transplants from brain-dead donors have been performed (only available in Japanese, http://www.asas.or.jp/jst/report_top.html). Why is there such a low incidence of transplants from brain-dead donors in Japan? Many of the medical professionals, as well as the patients who are waiting for a transplant and their families, believe that the law itself is a very serious obstacle. This law permits organ donation frombrain-dead donors only when they are older than 15, have a signed ‘donor card’ and also if their family does not reject either the brain-dead diagnosis or organ transplantation [10]. A national survey on organ transplant after brain death in 2006 showed that 8% of the adults may possess the donor card but only 40% of cardholders had described their intentions concerning organ donation properly (as validated in a documented will) (http://www.jotnw.or.jp/english/index.html). According to the National Survey of Incidence of Brain Death in 2006 (only available in Japanese, http://www.asas.or.jp/jst/pdf/20080212/about_plana.pdf), an incidence of brain death that could be applied towards donor transplantation was estimated to be around 3000/year in Japan. However, only 1601 transplants were actually performed with a diagnosis of ‘brain death’. This survey also speculated that the major reason for many ‘undiagnosed cases’ was because it put too much burden on the emergency room staff.
Kidney transplantation does not need to rely only on the brain-dead donor. However, transplantation from cardiac deaths has also been in the minority in Japan. In 2006, 1136 kidney transplants were performed. However, 939 cases (82.6%) were transplants from a living donor (182 cases from cardiac death and 15 cases from brain death). As shown in Figure 2, transplants from cardiac death even decreased after 1997 (only available in Japanese, http://www.asas.or.jp/jst/report_top.html). This can partly be explained by a misunderstanding of the law for brain death on the procedure for claiming death both by professionals and patient families. The increase in kidney transplantation by living donors has also been facilitated by the success of the ABO unmatched transplantation programme, which has increased kidney transplantation between spouses. Because of the very few kidney transplants from cadaver donors, ESRD patients waiting for a donor (11 513 in 2007) tend to prefer a living-related donor, if available [11].
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Another important fact that negatively influences the incidence of kidney transplantation in Japan may be the ignorance of transplantation by dialysis specialists. It is true that most dialysis specialists are not interested in kidney transplantation. Consequently, dialysis specialists do not offer their patients the proper information. Some doctors explain that there are fewer transplants due to better care and higher satisfaction of ESRD dialysis patients in Japan. In fact, according to the DOPPS study, Japanese patients showed higher quality of care scores in most categories by both SF-36 and KDQOL than patients in Europe [12]. However, I do not personally agree with this argument because a successful transplantation would give them much better QOL scores.
Japanese nephrologists and CKD initiative
The JSN celebrated its 50th anniversary in 2007. Almost 8000 doctors are currently members of JSN and 2834 doctors are board-certified nephrologists (by 1 April 2007). Almost 10 000 kidney biopsies are annually performed in Japan. This has resulted in a better treatment of CGN from an early stage because of the successful urine screening system and adequate referral to nephrologists in Japan. However, many patients with diabetes and hypertension were not diagnosed with CKD until in a very late stage, mainly due to ignorance of their kidney function by non-nephrologists. This can be improved. JSN publishes the modified MDRD equation with a Japanese racial coefficient based on <800 inulin clearance tests [13]. This would provide proper understanding of GFR among patients and non-nephrology medical professionals. JSN has established a joint initiative with the Japanese Society of Diabetes since 1998. This led to joint CKD initiatives with other CKD-related academic societies and policy makers in 2006. The governmental project, ‘Frontier Research of Outcome Modifications in Japan’ will spend 5 million US dollars over the next 5 years to study the effect of active intervention in the prevention of ESRD. The most effective initiative should be the early detection of CKD in diabetes and hypertension and improvement of patient adherence to treatment in Japan, just as in other countries.
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Acknowledgments |
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Conflict of interest statement. None declared.
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References |
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- Imai E, Yamagata K, Iseki K, et al. Kidney disease screening program in Japan: history, outcome, and perspectives. Clin J Am Soc Nephrol (2007) 2:1360–1366.
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Accepted in revised form: 3. 4.08
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