Why has the gross mortality of dialysis patients increased in Japan?

Kidney International, Vol. 57, Suppl. 74 (2000), pp. S-60 S-65 Why has the gross mortality of dialysis patients increased in Japan? MORTALITY TAKASHI AKIBA, SHIGERU NAKAI, TORU SHINZATO, CHIKAO YAMAZAKI, TATEKI KITAOKA, KAZUO KUBO, and KENJI MAEDA Patient Survey Committee, Japanese Society for Dialysis Therapy, Nagoya, Japan Why has the gross mortality of dialysis patients increased in ments came from continuous efforts to increase dialysis Japan? doses in hemodialysis and peritoneal dialysis patients, Background. The gross mortality of Japanese chronic dialas well as from implementation of a comprehensive apysis patients gradually increased from 8.1% in 1983 to 9.4% in 1997. We describe the demographic changes in dialysis paysis patients. In contrast, gross mortality of Japanese proach to prevent multi-systemic complications in dial- tients and clarify why the gross mortality has increased. Methods. Data used in our analysis were taken from annual chronic dialysis therapy has been reportedly increasing. reports by the Patient Registration Committee of the Japanese Our goals in this paper are to describe the demographic Society for Dialysis Therapy. The relative risk of death was calculated by a logistic regression procedure and Cox proporimproving chronic dialysis therapy. changes in dialysis patients and to clarify problems in tional hazard model. Results. The first-year survival starting from the initiation of dialysis therapy slowly improved from 0.836 in 1983 to 0.857 in 1996, but 5-year and 10-year survival consistently decreased METHODS in the same patient groups. The patients mean age of beginning Data used in this analysis were taken from the annual dialysis steadily increased from 51.9 in 1983 to 62.2 in 1997. The incidence of patients with diabetes as the original disease reports by the Patient Registration Committee of the showed a tremendous increase from 15.6% in 1983 to 33.9% in Japanese Society for Dialysis Therapy [4 9]. The Patient 1997, and patients with nephrosclerosis also showed a twofold Registration Committee s patient survey method has increase in our population. Heart failure accounted for 30 35% been described elsewhere [5 7]. Briefly, at the end of of mortality until 1991, but this started to decrease after 1992, November from 1968 onward, the committee mailed the when recombinant human erythropoietin became clinically available, and the level fell to 23.9% by 1997. The relative risk questionnaire form to the head doctors of all facilities of death in the first year of initiating dialysis therapy decreased listed in the society. The recipients were asked to return to almost half of the reference year 1983 (P 0.0001). the survey replies by the end of the following March. Conclusion. The increase in the gross mortality of Japanese The items surveyed were facility characteristics and dedialysis patients might not be due to a deteriorating quality of mographics. A longitudinal survey of first-time dialysis dialysis therapy, but rather is a reflection of accepting patients with older age and comorbid factors contributing to higher patients and subsequent follow-up of their clinical and risks of mortality with dialysis therapy. laboratory data was started in 1983. In 1994, we asked facilities to respond using a Lotus 1-2-3 or Microsoft Excel worksheet. This collection form was used by 986 In 1984, we described huge differences in the mortality facilities in 1998, making it possible to increase items of dialysis patients in the United States, Europe, and surveyed to include factors such as doses of erythropoie- Japan [1]. Life expectancy of dialysis patients age 45 64 tin, cardiothoracic ratio, and predialysis systolic and diayears in the United States was almost one-third of that stolic blood pressure. Response rates in 1997 were 99.7% for Japanese dialysis patients. Recent publications on for the items concerning facility status and 96.4% for the mortality of dialysis patients in the United States the patient longitudinal surveys. As of the end of 1997, have consistently reported significant improvements in 340,462 patients records had been registered in the pagross mortality of hemodialysis and peritoneal dialysis tient longitudinal survey. Data analysis was executed patients [2, 3]. These reports suggested that the improve- using SAS/STAT software (version 6.03, SAS Institute Japan, Tokyo). The relative risk of death was calculated Key words: survival, incidences, dialysis, aging, diabetic nephropathy, by a logistic regression procedure and Cox proportional ESRD hazard model as case-mix variables of gender, age, duration 2000 by the International Society of Nephrology on dialysis, and original diseases. Reports from the S-60

Akiba et al: Mortality of dialysis patients in Japan S-61 Fig. 1. Recent trends in the gross mortality (%/year) of dialysis patients in Japan, 1983 1997. Fig. 2. Trends in survival of dialysis patients at first ( ), fifth ( ), and tenth year ( ), by year. Patient Registry Committee of the Japanese Society for Dialysis Therapy were published annually [8]. The reports were distributed to all members and participating facilities at the annual meetings of the Japanese Society for Dialysis Therapy. Excerpts from the reports were published in the December issue of the Journal of the Japanese Society for Dialysis Therapy each year [9]. RESULTS The gross mortality rate of dialysis patients was 8.1% in 1983, gradually increasing to 9.4% in 1997 (Fig. 1). Survival of dialysis patients after the first year following the initiation of dialysis therapy slowly improved from 0.836 in 1983 to 0.857 in 1997 (Fig. 2). In contrast, fiveyear survival consistently decreased from 0.626 in patients who started dialysis in 1983 to 0.578 in patients who started dialysis in 1992. Ten-year survival also showed consistent declines. The mean age of patients beginning dialysis was 51.9 in 1983, steadily increasing to 62.2 in 1997 (Fig. 3). The mean age of patients receiving on-going dialysis treatment also showed an increase, from 48.3 in 1983 to 59.2 in 1997. The average life span of the Japanese population, expressed as a mean of males and females, was 76.99 in 1983 and gradually increased to 79.62 in 1994. Percent changes in the five main original diseases of patients initiating dialysis by the year in which dialysis Fig. 3. Trends in the average life span of Japanese population ( ), the mean age of incident patients ( ), and the mean age of the prevalent patients ( ), by year.

S-62 Akiba et al: Mortality of dialysis patients in Japan Fig. 4. Distribution of five main original diseases of incident patients by the year of the initiation of dialysis therapy. Fig. 5. Trends in the distribution of main causes of death of dialysis patients, 1983 1997. Recombinant erythropoietin became extensively administered in 1992. Rare and unknown causes are not shown. therapy was begun are given in Fig. 4, which shows a tremendous increase in diabetic patients from 15.6% in 1983 to 33.9% in 1997. Patients beginning dialysis who had nephrosclerosis also increased twofold, from 3.0% in 1983 to 6.8% in 1997. Patients starting dialysis who had chronic glomerulonephritis concomitantly decreased from 58.3% in 1983 to 36.6% in 1997, though the number of new dialysis patients increased from 5,750 in 1983 to 10,703 in 1997. The five main causes of death in dialysis patients were heart failure, malignancy, infection, myocardial infarction, and cerebrovascular accident (Fig. 5). Heart failure accounted for around 30 35% of mortality in 1991, but its incidence started to decrease from 1992, when recombinant human erythropoietin (rhuepo) became extensively administered, and the level fell to 23.9% by 1997. Twelve month survival of long-term dialysis patients differed significantly by hematocrit (Hct) levels at the end of 1994 (P 0.0001) (Fig. 6). Survival rates at the twelfth month were 0.761 for Hct 15%, 0.853 for Hct 15 20%, 0.897 for Hct 20 25%, 0.939 for Hct 25 30%, 0.950 for Hct 30 35%, 0.943 for Hct 35 40%, and 0.945 for Hct 40%. Relative risk of death after 1 year on dialysis was Fig. 6. Survival of prevalent patients during 12 months of 1995 by hematocrit (Hct) levels at the end of 1994.

Akiba et al: Mortality of dialysis patients in Japan S-63 Fig. 7. Relative risk of 1-year death adjusted by gender, age, duration on dialysis, and original diseases. (A) original diseases (, nondiabetic;, diabetes;, total), (B) age at initiation of dialysis therapy (, 30-44 years;, 45-59 years;, 60 74 years). adjusted by gender, age, duration on dialysis, and original coincided with the increase in the age of new dialysis disease. Relative risk of death by the year when dialysis patients (Fig. 3), the increase in patients with diabetic therapy started decreased to almost half of that in the nephropathy as an original disease (Fig. 4), and the 7.7% reference year 1983 (P 0.0001) (Fig. 7A). Relative risk and 11.5% decreases of 5-year and 10-year survival, re- of death of diabetes patients decreased to 0.346, though spectively (Fig. 2). that of non-diabetes patients moderately decreased to Better survival with higher hematocrit (Fig. 6) and the 0.614. percent reduction in deaths from congestive heart failure Relative risk of death was compared by the patient coinciding with the introduction of the clinical use of age at the initiation of dialysis therapy (Fig. 7B). There rhuepo (Fig. 5) might offset the degree of the increase did not appear to be any significant age-related differyear in gross mortality to some extent. The relative risk of 1- ence in risk at the start of the therapy. Relative risk of death in dialysis patients by the year when dialysis death was 0.531 for patients aged 30 44 years, 0.528 for therapy was initiated showed significant and continuous patients aged 45 59 years, and 0.429 for patients more improvements when that of 1983 was used as a reference than 60 years in 1995. year (Fig. 7A). The improvement in the relative risk of The changes in the addition of new patients and the death was greater in diabetic patients than in non-diadeath of dialysis patients in Japan were graphically comgroups betic patients. In contrast, the risks of death in three pared (Fig. 8). The incidence of initiation of therapy and based on age at the initiation of dialysis therapy mortality rapidly increased from 1983 to 1997, and the showed recent improvement, although the degree of im- annual difference, which stood for the annual increase provement was not different among them (Fig. 7B). of long-term dialysis patients, continuously increased The incidence of end-stage renal disease (ESRD) was over the same period. When the initiation incidence and suggested to show an exponential increase [2, 10]. The the number of deaths were plotted on a semilogarithmic United States Renal Data System (USRDS) reported scale, they both fitted to straight lines (r 2 0.990 and that incident patients in the United States doubled in 0.993, respectively). The slope of the mortality was 8.5 years [2]. Doubling occurred at a faster pace among steeper than that of initiation incidence. patients with diabetes (6 years) and hypertension (7 years) as causes of ESRD, as well as in elderly patients (6 years for age 75 to 84). Our observations in the Japanese DISCUSSION population also showed that the aging process of the Our analysis of data from the Patient Registry over population and demographic changes in original diseases the fifteen-year period from 1983 to 1997 disclosed that could be the main reasons for these exponential increases the death rate of dialysis patients showed a definite increase in new dialysis patients [11]. from around 8% to 9.5% (Fig. 1). This increase The annual death rates of dialysis patients in the

S-64 Akiba et al: Mortality of dialysis patients in Japan Fig. 8. Trends in incidence ( ) and mortality ( ) of dialysis patients in Japan. (A) standard scale; (B) semilogarithmic scale. rather to the changes in aging, original diseases, or un- measured factor(s). More aggressive approaches for the improvement of dialysis therapy might be needed to overcome the high risk of patients to be treated in the future. United States recently showed clear decreases, from 26% in 1988 to 23% in 1995 [3]. Reports have suggested that these decreases in annual mortality might be attributed to the increased delivery of dialysis dose, shift from cellulosic to synthetic hemodialysis membrane, and the use of erythropoietin [3, 11]. The increases in gross mortality from 8 9.5% we observed over the recent 15-year period in Japan suggest that Japanese physicians might be providing poor-quality dialysis therapy to their patients. Our analysis clearly indicated that the risk of death after 1 year adjusted by age, gender, original disease, and years on dialysis therapy significantly and continuously decreased with changes in the causes of death. The relative risk of death for patients with diabetes as a cause of ESRD in 1996 also decreased to one-third of that in 1983. The increase in the gross mortality of Japanese REFERENCES dialysis patients might not be due to deteriorating quality ACKNOWLEDGMENTS We gratefully acknowledge the staffs of all dialysis facilities in Japan for the generous cooperation with our survey. We also thank I. Matsu- moto for her secretarial work. Reprint requests to Takashi Akiba, M.D., Ph.D., Department of Internal Medicine and Blood Purification, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyoku, Tokyo 113-8519, Japan. E-mail: takiba.med2@med.tmd.ac.jp 1. Held PJ, Akiba T, Stearns NS, Murumo F, Turrene MN, Maeda of the dialysis therapy supplied, but rather a reflection K, Port FK: Survival of middle-aged dialysis patients in Japan and of accepting older, higher risk patients for dialysis. the US, 1988 89, in Developments in Nephrology, Volume 35, Death The slope of the mortality plot was steeper than that on Dialysis, edited by Friedman EA, Dordrecht, Kluwer Academic Publishers, 1994, pp 23 23. of the incidence plot on the semilogarithmic scale, sug- 2. U.S. Renal Data System: USRDS 1994 Annual Data Report gesting that the improvement of dialysis therapy could Bethesda, MD, National Institute of Health, National Institute of not overcome the increased risk in more elderly patients Diabetes and Digestive and Kidney Diseases, 1994. 3. U.S. Renal Data System: USRDS 1998 Annual Data Report, and those with a higher frequency of diabetic nephropa- Bethesda, MD, National Institute of Health, National Institute of thy. The prevalence of dialysis patients might decrease Diabetes and Digestive and Kidney Diseases, 1998 due to the future increase in mortality if the background 4. Marumo F, Maeda K, Koshikawa S: ESRD registry statistics on features of dialysis therapy such as the aging of the popu- dialysis mortality, in Developments in Nephrology, Volume 35, Death on Dialysis edited by Friedman EA, Dordrecht, Kluwer lation and changes in original diseases stay in the present Academic Publishers, 1994, pp 45 54 trend. The chronic dialysis therapy supplied in Japan 5. Shinzato T, Nakai S, Akiba T, Yamazaki C, Sasaki T, Kitaoka recently might face socioeconomic restrictions due to T, Kubo K, Shinoda T, Kurokawa K, Marumo F, Maeda K: Survival in long-term hemodialysis patients: results from the annual the prohibitive cost of treating a relatively small numsurvey of the Japanese Society for Dialysis Therapy. Nephrol Dial ber of patients with this therapy and due to the fear of Transplant 11:2139 2142, 1996 endless increases in the prevalence patients on dialysis 6. Shinzato T, Nakai S, Akiba T, Yamazaki C, Sasaki T, Kitaoka therapy. We conclude that the increase in the gross mor- T, Kubo K, Shinoda T, Kurokawa K, Murumo F, Maeda K: Current status of renal replacement therapy in Japan: results of tality of Japanese dialysis patients could not be attributed the annual survey of the Japanese Society for Dialysis Therapy. to the changes in the quality of dialysis therapy, but Nephrol Dial Transplant 11:2143 2150, 1996

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