Kidney Disease Screening Program in Japan: History, Outcome, and Perspectives

Special Feature: Screening Series Kidney Disease Screening Program in Japan: History, Outcome, and Perspectives Enyu Imai,* Kunihiro Yamagata,† Kunitoshi Iseki,‡ Hiroyasu Iso,§ Masaru Horio,* ʈ Hirofumi Mkino, Akira Hishida,¶ and Seiichi Matsuo** Departments of *Nephrology and §Public Health, Osaka University Graduate School of Medicine, Suita, Osaka, †Department of Nephrology, Institute of Clinical Medicine, Graduate School of Comprehensive Human Science, ʈ University of Tsukuba, Ibaraki, ‡Dialysis Unit, University Hospital of the Ryukyus, Okinawa, Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, ¶First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, and **Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan In the early 1970s, mandatory kidney disease screening was started with urinalysis in the Japanese health examination program for all workers and school-age children. In 1983, nationwide urinalysis screening in adults aged >40 yr was mandated in the community-based health examination program. Because glomerulonephritis was an endemic disease and the leading cause of end-stage renal disease in Japan until 1997, the urinalysis in the annual health examination program aimed for early detection of glomerulonephritis and early referral of patients to physicians. To the programs, measurement of serum creatinine was added for detection of chronic kidney disease in 1992 for adults aged >40 yr. Kidney disease screening and early intervention brought reduction of progressive glomerulonephritis or an increase in remission. Thus, in children and adults aged <45 yr, the number of patients with end-stage renal disease from glomerulonephritis has declined, and the mean age of patients with new end-stage renal disease has increased significantly. In 1998, the leading cause of end-stage renal disease was shifted from glomerulonephritis to diabetic nephropathy as a result of lifestyle changes in the Japanese population; however, the present comprehensive kidney disease screening in the health examination program for detection of glomerulonephritis must be continued, because even in 2005, 27.3% of newly developed end-stage renal disease was from glomerulonephritis. An additional kidney disease screening program should also be established to target patients with high risk for diabetes, hypertension, and metabolic syndrome, because 42% of newly introduced renal replacement cases were from diabetic nephropathy in 2005. Clin J Am Soc Nephrol 2: 1360–1366, 2007. doi: 10.2215/CJN.00980207 n epidemic of chronic kidney disease (CKD) is a History of Kidney Disease Screening of the worldwide health problem (1,2). It not only progress Health Examination Program in Japan A to the ESRD but also is a major risk factor for cardio- Concern about health problems in the Japanese workforce, the vascular disease (CVD) (3). Although every effort has been Ministry of Labor implemented a mandatory, nationwide, com- made to reduce CKD and the known leading causes of CKD— pany-based health examination program in 1973, including diabetes, hypertension, and metabolic syndrome—the past blood chemistry and urinalysis. In 1974, the Ministry of Edu- measures taken to treat these clinical conditions were insuffi- cation, Science and Culture initiated the mandatory school- cient. Eventually, the incidence of ESRD and CVD reached high based health examination program for school children aged 6 to in both developed and developing countries. In addition, many 18 to meet the requirement of the School Health Law. In the countries are burdened by their own endemic renal conditions program, urinalysis was performed to identify the early stage (4); IgA nephropathy (IgAN) in Asia (5); hepatitis B–related of glomerulonephritis in children. The screening, initially per- nephropathy in Asia and Africa; and HIV-associated nephrop- formed biannually, was reduced to annually in 1979. In 1983, athy in Africa, Asia, Europe, and the United States. Implement- the Ministry of Health and Welfare mandated the nationwide ing and establishing a kidney disease screening program is important to prevent CKD and particularly to detect in the community-based health examination program for adults aged Ն early stage of CKD. 40 yr by law, which included urinalysis. Since then, urinalysis in the annual health examination program has been accepted by the Japanese public. In 1992, measurement of serum creatinine level in adults aged Ն40 yr was added to both the com- Published online ahead of print. Publication date available at www.cjasn.org. pany-based and community-based annual health examination Correspondence: Dr. Enyu Imai, Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879- program for detection of CKD. The combination of urinalysis 3632; Fax: 81-6-6879-3639; E-mail: [email protected] and measurement of serum creatinine level has contributed to Copyright © 2007 by the American Society of Nephrology ISSN: 1555-9041/206–1360 Clin J Am Soc Nephrol 2: 1360–1366, 2007 Kidney Disease Screening Program in Japan 1361 detection of early-stage CKD in Japanese adults aged Ն40 yr. workers aged 20 to 60 (11,933,703 individuals) received urinal- The kidney disease screening implemented in Japan has been ysis tests. For the adults without full-time jobs, urinalysis and systemic and nationwide, covering both school-age children blood chemistry are available in the community-based health and adults. examination program, the same as the company-based screening programs. In general, approximately half of the people Practice of the Japanese Kidney Disease eligible participate in community-based health examination Screening and Public Policy program. After the workers retire, they participate in the com- Glomerulonephritis was an endemic disease in Japan and the munity-based screening program. With urinary protein ϩ1or primary cause of ESRD until 1997 (6). Because glomerulone- more, the participants receive the second screening test for phritis is easily diagnosed with proteinuria and hematuria, urinary protein. If both tests are positive, then they receive a urinalysis in the annual health examination program was ini- diagnosis of proteinuria. tially mandated to aim for identifying the early stage of glo- For adults aged Ն40 yr, the company- and community-based merulonephritis and for the early referral to a physician. Al- health examinations are carried out more extensively. The pro- though glomerulonephritis dropped to the second leading gram includes a chest x-ray; urinalysis; and blood chemistry, cause of ESRD in 1998, glomerulonephritis continued to be a including serum creatinine, aminotransferases, uric acid, blood major cause of ESRD. Even in 2005, still 27.3% of new ESRD glucose, total cholesterol, LDL cholesterol, triglycerides, and cases involved glomerulonephritis (6). HDL cholesterol. According to the Ministry of Health, Welfare The Minister of Health, Welfare and Labor has been making and Labor, 44% of Japanese adults who were aged Ն40 yr and an extensive effort to reduce the number of patients with ESRD. did not have full-time jobs (12,983,593 individuals) participated The main strategy has been to establish an effective communi- the kidney disease screening in the health examination pro- ty-, company-, and school-based kidney disease screening gram in 2004. system. A cross-sectional study reported that prevalence of proteinuria was 4.1% (12,238 of 298,537) when urinary protein in Screening Program for Children spontaneously voided fresh urine sample was measured by In Japan, all school children receive a free urinalysis in the dipstick test, and the criteria for proteinuria was urinary pro- school-based health examination program. Urinalysis is gener- tein ϩ1 or more (approximately Ͼ30 mg/dl) (9). According to ally carried out in three stages. Proteinuria is verified by two a study conducted in 1983 in Okinawa, proteinuria and hema- consecutive positive results of the tests. The first screening is turia both tested with dipstick methods occurred in 5.3 and carried out in all school children by dipstick urinalysis. Chil- 9.0% of the general population, respectively (10). In an average dren are instructed to empty the bladder completely before 6.3-yr follow-up study, new proteinuria developed in 0.4 to sleep; the next morning, the first urine sample is brought to 0.9% of the Japanese working men, and among those with school for urinalysis. Dipstick urinalysis mainly detects protein proteinuria, 20% had persistent proteinuria and 75% received a and occult blood in urine. The second screening tests are per- diagnosis of chronic glomerulonephritis by biopsy (11). Yama- formed within 1 to 3 mo from the first screening for the children gata et al. (12) reported that newly developed proteinuria was who had proteinuria or hematuria in the first test. The child found in 0.61% of men and in 0.34% of women annually on the with two consecutive positive results receives a diagnosis of basis of community-based health examination programs for CKD, and the school physician suggests that that child see the adults aged Ն40 yr. In contrast, the prevalence of proteinuria family physician. The family physician generally checks serum was 0.01% in men and 0.19% in women of the screened popu- creatinine, urea nitrogen, uric acid, total protein, albumin, IgA, lation in the United States

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