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Brief Report |

Regional Variations in the Incidence of End-Stage Renal Failure in Japan FREE

Takeshi Usami, MD; Katsushi Koyama, MD; Oki Takeuchi, MD; Kunio Morozumi, MD; Genjiro Kimura, MD
[+] Author Affiliations

Author Affiliations: Department of Internal Medicine and Pathophysiology, Nagoya City University Medical School, Nagoya, Japan.


JAMA. 2000;284(20):2622-2624. doi:10.1001/jama.284.20.2622.
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Context Despite recent medical advances, the number of patients beginning dialysis annually is increasing in both the United States and Japan. The ethnically homogeneous population of Japan presents an opportunity to study the presence of factors other than race/ethnicity that might contribute to incidence of end-stage renal disease (ESRD).

Objective To determine if and where regional differences exist in ESRD in Japan.

Design, Setting, and Subjects Analysis of data reported by the Japanese Society for Dialysis Therapy based on the annual number of patients with ESRD beginning maintenance dialysis therapy in all 47 prefectures of Japan from 1982 to 1998.

Main Outcome Measures Mean annual ESRD incidence and increasing rate of ESRD in each of 11 predefined areas making up the entire country.

Results Incidence of ESRD increased approximately 3-fold in Japan during the study years, from 81.3 per 1 million in 1982 to 237.6 per 1 million in 1998. Significant regional differences were found in both measures. The mean (SEM) annual ESRD incidence (P<.01) and increasing rate of ESRD (P<.01), respectively, were significantly different across Japan. Koshinetsu (140 [11] per 1 million and 9.1 [0.6] per 1 million/y) and Hokuriku (141 [12] per 1 million and 9.7 [0.5] per 1 million/y) were the areas with the lowest incidence and increasing rate of incidence, while Okinawa (188 [17] per 1 million and 13.4 [0.6] per 1 million/y) and Kyushu (179 [15] per 1 million and 12.0 [0.6] per 1 million/y) were the areas with the highest incidence and increasing rate of incidence.

Conclusions We found definite and significant regional differences in incidence and increasing rate of incidence of ESRD in Japan. Further analyses are needed to identify factors that contribute to these regional differences and thereby improve strategies for treatment of renal disease.

Figures in this Article

Despite recent advances in nephrology and dramatic decreases in the incidence of cardiovascular diseases,1 the number of patients beginning dialysis therapy annually is increasing in both the United States2 and Japan.3 In the United States, racial differences in the incidence of end-stage renal disease (ESRD) have been noted.4,5 On the other hand, Japan has a relatively homogeneous racial composition. Therefore, we constructed maps to compare the annual incidence of ESRD and the increasing rate of ESRD incidence among different areas in Japan. Regional differences in Japan may suggest the presence of factors other than race that contribute to differences in incidence and increasing rate of incidence and that may be controllable by treatment.

Based on the numbers of patients with ESRD beginning maintenance dialysis therapy (both hemodialysis and peritoneal dialysis) annually in the 17-year period from 1982 to 1998 reported as an overview of regular dialysis treatment in Japan by the Japanese Society for Dialysis Therapy,3 we calculated the mean annual ESRD incidence and the increasing rate of ESRD incidence in each area for 11 areas comprising the entire country to construct maps on renal failure in Japan.

The 47 prefectures of Japan were organized into 11 areas that have internally homogeneous cultural and socioeconomic activities that differ between regions. Incorporation of data based on prefecture into larger units based on area should decrease errors due to the influx and efflux of the population that occur across the prefecture lines but that is mostly restricted to within a given area. Division into 11 areas (Hokkaido, Tohoku, Kanto, Koshinetsu, Hokuriku, Tokai, Kinki, Chyugoku, Shikoku, Kyushu, and Okinawa) was based on conventionally used and widely accepted definitions.

Annual ESRD Incidence and Increasing Rate of ESRD Incidence

The mean annual incidence of ESRD in each area (per population of 1 million) was calculated as the average in the area for the 17-year period from 1982 to 1998 of the number of patients with ESRD annually beginning dialysis therapy in prefectures3 and corrected for population in prefectures in each year. The increasing rate of ESRD incidence in each area (per population of 1 million per year) was calculated as the slope of regression lines between the annual incidence of ESRD in the area corrected for population and the year during 17 years.

Factors Related to Regional Differences in ESRD

We examined factors that might affect regional differences in ESRD dynamics. These were estimated from data based on prefectures for each area and included the average age of patients with ESRD entering dialysis therapy in 1998,3 the average percentage of people older than 65 years in 1998,6 the cost of medical care per 1 person in 1995,7 the number of nephrologists per general population in 1997,8 and the number of hospital beds available for dialysis therapy in 1997.9

Statistical Analysis

One-way repeated-measures analysis of variance (ANOVA) was used to compare the mean annual incidence of ESRD among areas, while 1-way ANOVA was used for the increasing rate of ESRD incidence, followed by the Newman-Keuls multiple comparison test. Pearson product moment correlation was used to examine the correlation among areas. Numeric data were expressed as the mean (SEM), and P<.05 was considered statistically significant.

Annual ESRD Incidence and Increasing Rate of ESRD Incidence

The number of patients with ESRD newly beginning maintenance dialysis in Japan increased from 4652 in 1982 to 30,051 in 1998, an approximately 3-fold increase in incidence from 81.3 to 237.6 per 1 million population. The average age of patients was 50.8 years in 1982 and 62.7 years in 1998. The major causes of ESRD were chronic glomerulonephritis (59.6% and 35.0% in 1982 and 1998, respectively) and diabetic nephropathy (13.7% in 1982 and 35.7% in 1998).

The mean annual ESRD incidence and the increasing rate of ESRD incidence in each area between 1982 and 1998 are shown in Table 1. Differences in the 2 measures among 11 areas were significant (P<.01) based on ANOVA.

Table Graphic Jump LocationTable. Regional Difference in End-Stage Renal Disease Dynamics
Maps of Renal Failure in Japan

To construct the maps (Figure 1) of renal failure in Japan, areas were classified into 3 categories: the lowest 3, the highest 3, and other intermediate areas, for incidence and increasing rate of ESRD, respectively. The maps illustrate that the mean annual incidence and the increasing rate of incidence were both low in Koshinetsu and Hokuriku, but were high in Okinawa and Kyushu. Figure 2 shows the comparison of the annual incidence of ESRD from 1982 to 1998 among these 4 areas. There were significant differences between the 2 regions with the lowest incidence and increasing rates (Koshinetsu and Hokuriku) and 2 regions with the highest (Okinawa and Kyushu) for both the mean annual incidence (P<.001) and the increasing rate (P<.05).

Figure 1. Maps of Incidence and Increasing Rate of Incidence of End-Stage Renal Disease in Japan
Graphic Jump Location
A, Regional difference in the mean annual incidence of end-stage renal disease (ESRD) in the 17-year period from 1982 to 1998. B, Increasing rate of ESRD incidence. Areas are classified into 3 categories: the 3 areas with the lowest incidence or increasing rates (light tint), the 3 areas with the highest incidence or increasing rates (dark tint), and areas with intermediate incidence or increasing rates (no tint). Numbers indicate 1, Hokkaido; 2, Tohoku; 3, Kanto; 4, Koshinetsu; 5, Hokuriku; 6, Tokai; 7, Kinki; 8, Chyugoku; 9, Shikoku; 10, Kyushu; and 11, Okinawa.
Figure 2. Comparison of the Annual Incidence of End-Stage Renal Disease in the 17-Year Period From 1982 to 1998 Among Areas With the Highest and Lowest Mean Annual Incidence and Increasing Rate of Incidence
Graphic Jump Location
In the mean annual incidence, there were significant differences (P<.001) between the areas with the lowest annual incidence (Koshinetsu and Hokuriku) and the areas with the highest annual incidence (Okinawa and Kyushu). There also was a significant difference between the areas with the highest incidence, Okinawa and Kyushu (P<.001), although no difference was seen between the areas with the lowest incidence, Koshinetsu and Hokuriku. For the increasing rate of incidence, there were significant differences (P<.05) between the areas with the lowest increasing rates (Koshinetsu and Hokuriku) and those with the highest (Okinawa and Kyushu). There were no significant differences within the same areas between Koshinetsu and Hokuriku or between Okinawa and Kyushu.
Factors Correlated With Regional Differences in ESRD

The number of hospital beds for dialysis therapy was significantly related to both the mean annual incidence (r = 0.92; P<.001) and the increasing rate (r = 0.67; P = .02). None of the other factors examined, such as average age of patients, percentage of the population older than 65 years, cost of medical care, or the number of nephrologists was correlated with the mean annual incidence and increasing rate of incidence.

Our data indicate the presence of clear regional differences within Japan in both the annual incidence of patients with ESRD beginning maintenance dialysis therapy and the increasing rate of ESRD incidence from 1982 to 1998. For example, the mean annual incidence and the increasing rate were both lowest in Koshinetsu, with annual incidence 1.3 times lower than that in Okinawa and the increasing rate 1.5 times lower than in Hokkaido. The Japanese Society for Dialysis Therapy3 has reported the absolute number of patients beginning dialysis therapy in each prefecture annually for 17 years without correcting for population. Therefore, the regional differences presented here have not been previously noted.

To our knowledge, this is the first study demonstrating the regional differences in ESRD dynamics within a relatively homogenous national population. Although studies have shown that hypertension and renal failure are more common among blacks than whites in the United States,4,5 no regional differences have been reported within a relatively homogeneous national population. Incidence of hypertension1013 and stroke1315 are known to vary by region in Japan, both being high in northern Japan and low in the southern part of the country. Association between hypertension and the amount of salt intake, proven in Japan,1013 is well known.12,13,16,17

Once regional differences in ESRD dynamics have been established, the factors affecting the differences must be elucidated. If we can identify such factors, it may be possible to improve strategies to prevent renal failure. We analyzed several factors to determine whether they were related to the regional differences in ESRD dynamics and found that only the number of beds available for dialysis therapy was correlated with regional differences. However, this is probably the result of increased numbers of patients with ESRD, rather than a causative factor. The dynamics of ESRD are determined by both the incidence of nephropathy and the progression rate. Lack of clear evidence concerning regional differences in the incidence of glomerulonephritis and diabetic nephropathy within Japan may suggest that the progression rate of nephropathy differs among geographic areas, but the current evidence does not allow us to reach any conclusions.

Recently, it has been noted that despite dramatic decreases in the incidences of stroke and ischemic heart disease, the incidence of ESRD increased by almost 3-fold in the 14-year period between 1982 and 1995 in the United States.1,2 Our data show a similar trend in Japan, with the incidence of ESRD increasing approximately 3-fold in the 17-year period between 1982 and 1998. Therefore, it is extremely important to determine the risk factors, especially modifiable risk factors, leading to ESRD. Angiotensin-converting enzyme inhibitor is now considered 1 of the most promising interventions for arresting renal failure.1820 If the factors contributing to the regional differences in ESRD dynamics can be identified, new strategies for treatment of renal disease should become available. Thus, further studies of regional differences in ESRD dynamics are needed. We hope that the present study will stimulate such analyses because the regional differences in ESRD dynamics appear definite and significant.

 The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.  Arch Intern Med.1997;157:2413-2446.
 United States Renal Data System: USRDS 1998 Annual Data Report . Bethesda, Md: US Dept of Health and Human Services; 1999.
 An Overview of Regular Dialysis Treatment in Japan [as of December 31, 1998]. Tokyo: Japanese Society for Dialysis Therapy: 1999.
Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Stamler J. End-stage renal disease in African-American and white men: 16-year MRFIT findings.  JAMA.1997;277:1293-1298.
Whittle JC, Whelton PK, Seidler AJ, Klag MJ. Does racial variation in risk factors explain black-white differences in the incidence of hypertensive end-stage renal disease?  Arch Intern Med.1991;151:1359-1364.
 Statistics Bureau and Statistics Center: Annual Report on Current Population Estimates [as of October 1, 1998]. Tokyo: Management and Coordination Agency of Japan; 1998.
Ministry of Health and Welfare.  Map of National Health Insurance Health Care CostsTokyo, Japan: Ministry of Health and Welfare; 1995.
 Japanese Society of Nephrology Membership Directory . Tokyo: Japanese Society of Nephrology; 1997.
 Institutional Membership Directory, Japanese Society for Dialysis Therapy . Tokyo: Japanese Society for Dialysis Therapy; 1997.
Sasaki N. High blood pressure and the salt intake of the Japanese.  Jpn Heart J.1962;3:312-324.
Kawamura M, Kimura Y, Takahashi K.  et al.  Relation of urinary sodium excretion to blood pressure, glucose metabolism, and lipid metabolism in residents of an area of Japan with high sodium intake.  Hypertens Res.1997;20:287-293.
Dahl LK. Possible role of chronic excess salt consumption in the pathogenesis of essential hypertension.  Am J Cardiol.1961;8:571-575.
Stamler J. The INTERSALT Study: background, methods, findings, and implications.  Am J Clin Nutr.1997;65(suppl 2):626S-642S.
Tanaka H, Tanaka Y, Hayashi M.  et al.  Secular trends in mortality for cerebrovascular diseases in Japan, 1960 to 1979.  Stroke.1982;13:574-581.
Omura T, Hisamatsu S, Takizawa Y, Minowa M, Yanagawa H, Shigematsu I. Geographical distribution of cerebrovascular disease mortality and food intakes in Japan.  Soc Sci Med.1987;24:401-407.
Joossens JV, Geboers J. Salt and hypertension.  Prev Med.1983;12:53-59.
MacGregor GA. Salt: more adverse effects [review].  Am J Hypertens.1997;10:37S-41S.
Zatz R, Dunn BR, Meyer TW, Anderson S, Renneke HG, Brenner BM. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertenstion.  J Clin Invest.1986;77:1925-1930.
Anderson S, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat.  J Clin Invest.1986;77:1993-2000.
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD.for the Collaborative Study Group.  The Effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy.  N Engl J Med.1993;329:1456-1462.

Figures

Figure 1. Maps of Incidence and Increasing Rate of Incidence of End-Stage Renal Disease in Japan
Graphic Jump Location
A, Regional difference in the mean annual incidence of end-stage renal disease (ESRD) in the 17-year period from 1982 to 1998. B, Increasing rate of ESRD incidence. Areas are classified into 3 categories: the 3 areas with the lowest incidence or increasing rates (light tint), the 3 areas with the highest incidence or increasing rates (dark tint), and areas with intermediate incidence or increasing rates (no tint). Numbers indicate 1, Hokkaido; 2, Tohoku; 3, Kanto; 4, Koshinetsu; 5, Hokuriku; 6, Tokai; 7, Kinki; 8, Chyugoku; 9, Shikoku; 10, Kyushu; and 11, Okinawa.
Figure 2. Comparison of the Annual Incidence of End-Stage Renal Disease in the 17-Year Period From 1982 to 1998 Among Areas With the Highest and Lowest Mean Annual Incidence and Increasing Rate of Incidence
Graphic Jump Location
In the mean annual incidence, there were significant differences (P<.001) between the areas with the lowest annual incidence (Koshinetsu and Hokuriku) and the areas with the highest annual incidence (Okinawa and Kyushu). There also was a significant difference between the areas with the highest incidence, Okinawa and Kyushu (P<.001), although no difference was seen between the areas with the lowest incidence, Koshinetsu and Hokuriku. For the increasing rate of incidence, there were significant differences (P<.05) between the areas with the lowest increasing rates (Koshinetsu and Hokuriku) and those with the highest (Okinawa and Kyushu). There were no significant differences within the same areas between Koshinetsu and Hokuriku or between Okinawa and Kyushu.

Tables

Table Graphic Jump LocationTable. Regional Difference in End-Stage Renal Disease Dynamics

References

 The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.  Arch Intern Med.1997;157:2413-2446.
 United States Renal Data System: USRDS 1998 Annual Data Report . Bethesda, Md: US Dept of Health and Human Services; 1999.
 An Overview of Regular Dialysis Treatment in Japan [as of December 31, 1998]. Tokyo: Japanese Society for Dialysis Therapy: 1999.
Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Stamler J. End-stage renal disease in African-American and white men: 16-year MRFIT findings.  JAMA.1997;277:1293-1298.
Whittle JC, Whelton PK, Seidler AJ, Klag MJ. Does racial variation in risk factors explain black-white differences in the incidence of hypertensive end-stage renal disease?  Arch Intern Med.1991;151:1359-1364.
 Statistics Bureau and Statistics Center: Annual Report on Current Population Estimates [as of October 1, 1998]. Tokyo: Management and Coordination Agency of Japan; 1998.
Ministry of Health and Welfare.  Map of National Health Insurance Health Care CostsTokyo, Japan: Ministry of Health and Welfare; 1995.
 Japanese Society of Nephrology Membership Directory . Tokyo: Japanese Society of Nephrology; 1997.
 Institutional Membership Directory, Japanese Society for Dialysis Therapy . Tokyo: Japanese Society for Dialysis Therapy; 1997.
Sasaki N. High blood pressure and the salt intake of the Japanese.  Jpn Heart J.1962;3:312-324.
Kawamura M, Kimura Y, Takahashi K.  et al.  Relation of urinary sodium excretion to blood pressure, glucose metabolism, and lipid metabolism in residents of an area of Japan with high sodium intake.  Hypertens Res.1997;20:287-293.
Dahl LK. Possible role of chronic excess salt consumption in the pathogenesis of essential hypertension.  Am J Cardiol.1961;8:571-575.
Stamler J. The INTERSALT Study: background, methods, findings, and implications.  Am J Clin Nutr.1997;65(suppl 2):626S-642S.
Tanaka H, Tanaka Y, Hayashi M.  et al.  Secular trends in mortality for cerebrovascular diseases in Japan, 1960 to 1979.  Stroke.1982;13:574-581.
Omura T, Hisamatsu S, Takizawa Y, Minowa M, Yanagawa H, Shigematsu I. Geographical distribution of cerebrovascular disease mortality and food intakes in Japan.  Soc Sci Med.1987;24:401-407.
Joossens JV, Geboers J. Salt and hypertension.  Prev Med.1983;12:53-59.
MacGregor GA. Salt: more adverse effects [review].  Am J Hypertens.1997;10:37S-41S.
Zatz R, Dunn BR, Meyer TW, Anderson S, Renneke HG, Brenner BM. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertenstion.  J Clin Invest.1986;77:1925-1930.
Anderson S, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat.  J Clin Invest.1986;77:1993-2000.
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD.for the Collaborative Study Group.  The Effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy.  N Engl J Med.1993;329:1456-1462.

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