Clinical and Experimental Nephrology

, Volume 14, Issue 2, pp 144–151 | Cite as

Design and methods of a strategic outcome study for chronic kidney disease: Frontier of Renal Outcome Modifications in Japan

  • Kunihiro Yamagata
  • Hirofumi Makino
  • Tadao Akizawa
  • Kunitoshi Iseki
  • Sadayoshi Itoh
  • Kenjiro Kimura
  • Daisuke Koya
  • Ichiei Narita
  • Tetsuya Mitarai
  • Masanobu Miyazaki
  • Yoshiharu Tsubakihara
  • Tsuyoshi Watanabe
  • Takashi Wada
  • Osamu Sakai
  • Advisory Committee for FROM-J
Original Article



The continuous increase in the number of people requiring dialysis is a major clinical and socioeconomical issue in Japan and other countries. This study was designed to encourage chronic kidney disease (CKD) patients to consult a physician, enhance cooperation between nephrologists and general practices, and prevent the progression of kidney disease.


Subjects comprise CKD patients aged between 40 and 74 years consulting a general physician, and patients in CKD stage 3 with proteinuria and diabetes or hypertension. This trial is a stratified open cluster-randomized study with two intervention groups: group A (weak intervention) and group B (strong intervention). We have recruited 49 local medical associations (clusters) in 15 different prefectures, which were classified into four regions (strata) based on the level of increase rate of dialysis patients. The patients in group A clusters were instructed initially to undergo treatment in accordance with the current CKD treatment guide, whereas patients in group B clusters were not only instructed in the same fashion but also received support from an information technology (IT)-based system designed to help achieve the goals of CKD treatment, consultation support centers, and consultations by dietitians visiting the local general practice offices. We assessed the rates of continued consultation, collaboration between general practitioners and nephrologists, and progression of CKD (as expressed by CKD stage).


Through this study, filling the evidence-practice gap by facilitating effective communication and supporting general physicians and nephrologists, we will establish a CKD care system and decrease the number of advanced-stage CKD patients.


Chronic kidney disease Evidence-practice gap Cluster-randomized study Educational intervention Cooperation between nephrologists and general physicians 



We express our thanks to the doctors and dietitians who participated in this study. We also express our thanks for the continuous support from members of the Japanese Society of Nephrology, the Japan Dietetic Association, and the Japanese Medical Association. We further thank Dr. Toshiyuki Imasawa, Dr. Chie Saitoh, Dr. Hirayasu Kai, Dr. Hideto Takahashi, Dr. Masafumi Okada, and Ms. Mariko Doi for valuable discussion and preparation of this manuscript. This study was supported by a grant for a strategic outcome study project from the Ministry of Health, Labor, and Welfare of Japan.


  1. 1.
    Nakai S, Masakane I, Akiba T, Iseki K, Watanabe Y, Itami N, et al. Overview of regular dialysis treatment in Japan (as of 31 December 2005). Ther Apher Dial. 2007;11:411–41.CrossRefPubMedGoogle Scholar
  2. 2.
    Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108:2154–69.CrossRefPubMedGoogle Scholar
  3. 3.
    Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32:S112–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Imai E, Horio M, Watanabe T, Iseki K, Yamagata K, Hara S, et al. Prevalence of chronic kidney disease (CKD) in Japanese general population. Clin Exp Nephrol, 2009.Google Scholar
  5. 5.
    Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med. 2001;134:629–36.PubMedGoogle Scholar
  6. 6.
    Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305.CrossRefPubMedGoogle Scholar
  7. 7.
    Hillege HL, Girbes AR, de Kam PJ, Boomsma F, de Zeeuw D, Charlesworth A, et al. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation. 2000;102:203–10.PubMedGoogle Scholar
  8. 8.
    Brugts JJ, Knetsch AM, Mattace-Raso FU, Hofman A, Witteman JC. Renal function and risk of myocardial infarction in an elderly population: the Rotterdam Study. Arch Intern Med. 2005;165:2659–65.CrossRefPubMedGoogle Scholar
  9. 9.
    K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002; 39:S1–266.Google Scholar
  10. 10.
    Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005;67:2089–100.CrossRefPubMedGoogle Scholar
  11. 11.
    Yamagata K, Takahashi H, Suzuki S, Mase K, Hagiwara M, Shimizu Y, et al. Age distribution and yearly changes in the incidence of end-stage renal disease in Japan. Am J Kidney Dis. 2004;43:433–43.CrossRefPubMedGoogle Scholar
  12. 12.
    Sorensen VR, Hansen PM, Heaf J, Feldt-Rasmussen B. Stabilized incidence of diabetic patients referred for renal replacement therapy in Denmark. Kidney Int. 2006;70:187–91.CrossRefPubMedGoogle Scholar
  13. 13.
    Yamagata K, Ishida K, Sairenchi T, Takahashi H, Ohba S, Shiigai T, et al. Risk factors for chronic kidney disease in a community-based population: a 10-year follow-up study. Kidney Int. 2007;71:159–66.CrossRefPubMedGoogle Scholar
  14. 14.
    Heagerty A. Optimizing hypertension management in clinical practice. J Hum Hypertens. 2006;20:841–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Usami T, Nakao N, Fukuda M, Takeuchi O, Kamiya Y, Yoshida A, et al. Maps of end-stage renal disease and amounts of angiotensin-converting enzyme inhibitors prescribed in Japan. Kidney Int. 2003;64:1445–9.CrossRefPubMedGoogle Scholar
  16. 16.
    CKD Clinical Practice Guidelines: Japanese Society of Nephrology (written and edited), First edition, Tokyo Igakusha, 2007.Google Scholar
  17. 17.
    Usami T, Koyama K, Takeuchi O, Morozumi K, Kimura G. Regional variations in the incidence of end-stage renal failure in Japan. JAMA. 2000;284:2622–4.CrossRefPubMedGoogle Scholar
  18. 18.
    Imai E, Horio M, Yamagata K, Iseki K, Hara S, Ura N, et al. Slower decline of glomerular filtration rate in the Japanese general population: a longitudinal 10-year follow-up study. Hypertens Res. 2008;31:433–41.CrossRefPubMedGoogle Scholar
  19. 19.
    Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–60.CrossRefPubMedGoogle Scholar
  20. 20.
    Churchill DN, Blake PG, Jindal KK, Toffelmire EB, Goldstein MB. Clinical practice guidelines for initiation of dialysis. Canadian Society of Nephrology. J Am Soc Nephrol. 1999;10(Suppl 13):S289–91.PubMedGoogle Scholar
  21. 21.
    Burden R, Tomson C. Identification, management and referral of adults with chronic kidney disease: concise guidelines. Clin Med. 2005;5:635–42.PubMedGoogle Scholar
  22. 22.
    Nicholls K. Prevention of progression of kidney disease: diabetic nephropathy—CARI guidelines. Aust Fam Physician. 2007;36:137–8.PubMedGoogle Scholar
  23. 23.
    IV. NKF-K/DOQI Clinical practice guidelines for anemia of chronic kidney disease: update 2000. Am J Kidney Dis. 2001; 37:S182–238.Google Scholar
  24. 24.
    Neumann ME. Results in KEEP’s first report show progress in early identification of CKD patients. Nephrol News Issues. 2003;17:84–7.PubMedGoogle Scholar
  25. 25.
    Yamagata K, Takahashi H, Tomida C, Yamagata Y, Koyama A. Prognosis of asymptomatic hematuria and/or proteinuria in men. Nephron. 2002;91:34–42.CrossRefPubMedGoogle Scholar
  26. 26.
    Ishida K, Ishida H, Narita M, Sairenchi T, Saito Y, Fukutomi H, et al. Factors affecting renal function in 119 985 adults over three years. QJM. 2001;94:541–50.CrossRefPubMedGoogle Scholar
  27. 27.
    Ninomiya T, Kiyohara Y, Kubo M, Yonemoto K, Tanizaki Y, Doi Y, et al. Metabolic syndrome and CKD in a general Japanese population: the Hisayama Study. Am J Kidney Dis. 2006;48:383–91.CrossRefPubMedGoogle Scholar
  28. 28.
    Orth SR, Hallan SI. Smoking: a risk factor for progression of chronic kidney disease and for cardiovascular morbidity and mortality in renal patients—absence of evidence or evidence of absence?. Clin J Am Soc Nephrol. 2008;3:226–36.CrossRefPubMedGoogle Scholar
  29. 29.
    The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993; 329:977–86.Google Scholar
  30. 30.
    Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28:103–17.CrossRefPubMedGoogle Scholar
  31. 31.
    Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36:646–61.PubMedGoogle Scholar
  32. 32.
    Schaeffner ES, Kurth T, Curhan GC, Glynn RJ, Rexrode KM, Baigent C, et al. Cholesterol and the risk of renal dysfunction in apparently healthy men. J Am Soc Nephrol. 2003;14:2084–91.PubMedGoogle Scholar
  33. 33.
    Iseki K, Ikemiya Y, Iseki C, Takishita S. Proteinuria and the risk of developing end-stage renal disease. Kidney Int. 2003;63:1468–74.CrossRefPubMedGoogle Scholar
  34. 34.
    Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The angiotensin-converting-enzyme inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med. 1996;334:939–45.CrossRefPubMedGoogle Scholar
  35. 35.
    Lewis JB, Berl T, Bain RP, Rohde RD, Lewis EJ. Effect of intensive blood pressure control on the course of type 1 diabetic nephropathy. Collaborative Study Group. Am J Kidney Dis. 1999;34:809–17.CrossRefPubMedGoogle Scholar
  36. 36.
    Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–9.CrossRefPubMedGoogle Scholar
  37. 37.
    Halbesma N, Kuiken DS, Brantsma AH, Bakker SJ, Wetzels JF, De Zeeuw D, et al. Macroalbuminuria is a better risk marker than low estimated GFR to identify individuals at risk for accelerated GFR loss in population screening. J Am Soc Nephrol. 2006;17:2582–90.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2009

Authors and Affiliations

  • Kunihiro Yamagata
    • 1
  • Hirofumi Makino
    • 2
  • Tadao Akizawa
    • 3
  • Kunitoshi Iseki
    • 4
  • Sadayoshi Itoh
    • 5
  • Kenjiro Kimura
    • 6
  • Daisuke Koya
    • 7
  • Ichiei Narita
    • 8
  • Tetsuya Mitarai
    • 9
  • Masanobu Miyazaki
    • 10
  • Yoshiharu Tsubakihara
    • 11
  • Tsuyoshi Watanabe
    • 12
  • Takashi Wada
    • 13
  • Osamu Sakai
    • 14
  • Advisory Committee for FROM-J
  1. 1.Department of Nephrology, Institute of Clinical Medicine, Graduate School of Comprehensive Human SciencesUniversity of TsukubaTsukubaJapan
  2. 2.Department of Medicine and Clinical ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  3. 3.Division of Nephrology, Department of MedicineShowa University School of MedicineTokyoJapan
  4. 4.Dialysis UnitUniversity Hospital of The RyukyusOkinawaJapan
  5. 5.Division of Nephrology, Endocrinology and Vascular MedicineTohoku University Graduate School of MedicineMiyagiJapan
  6. 6.Department of Nephrology and HypertensionSt. Marianna University School of MedicineKanagawaJapan
  7. 7.Division of Endocrinology and MetabolismKanazawa Medical UniversityIshikawaJapan
  8. 8.Division of Clinical Nephrology and RheumatologyNiigata University Graduate School of Medical and Dental ScienceNiigataJapan
  9. 9.Division of Nephrology and Hypertension, Saitama Medical CenterSaitama Medical SchoolSaitamaJapan
  10. 10.Department of Internal MedicineMiyazaki ClinicMiyazakiJapan
  11. 11.Department of NephrologyOsaka General Medical CenterOsakaJapan
  12. 12.Department of Internal Medicine IIIFukushima Medical University School of MedicineFukushimaJapan
  13. 13.Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of MedicineKanazawa UniversityIshikawaJapan
  14. 14.Japan Kidney FoundationTokyoJapan

Personalised recommendations