Chronic Kidney Disease (CKD) as an Emerging Risk Factor in the Elderly

  • Kunitoshi Iseki
Part of the Current Topics in Environmental Health and Preventive Medicine book series (CTEHPM)


Chronic kidney disease (CKD) is becoming an increasingly prevalent clinical entity, and its severity is defined by the combination of albuminuria (proteinuria) and the glomerular filtration rate (GFR). Chronicity denotes 3 months and longer. CKD was first recognized as a risk factor for CVD by cardiologists, but the association of CKD with many other diseases, such as bone, muscle, and gastrointestinal diseases, stroke (cognitive function), malignancies, and infection, has become increasingly recognized.

The term “elderly” is used for persons ≥65 years of age, whereas “very elderly” is reserved for persons ≥80 years of age. Chronologic age is used as a surrogate for biologic age, although this relationship is highly variable. The leading cause of end-stage renal disease (ESRD) requiring dialysis therapy is DM, which accounts for approximately 44% of the total in Japan.

The elderly population is rapidly increasing in both developed and developing countries, and Japan has the highest rate of increase. The screening system for CKD is highly developed in Japan and begins with school children through the general population. Signs and symptoms associated with normal aging may, at least partly, be explained by the physiologic decline in the GFR.

The clinical relevance of CKD among the elderly population is becoming more evident. More studies of patient reported outcomes are needed for the development of clinical practice guidelines.


Proteinuria Glomerular filtration rate (GFR) Chronic kidney disease (CKD) Cardiovascular disease (CVD) End-stage renal disease (ESRD) 


  1. 1.
    Levey A, de Jong PE, Coresh J, et al. Chronic kidney disease—definition, classification and prognosis: a KDIGO controversies conference report. Kidney Int. 2011;80:17–28.CrossRefGoogle Scholar
  2. 2.
    Sarnak MJ, Levey AS, Schoolwerth AC, 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.CrossRefGoogle Scholar
  3. 3.
    The Japanese Society for Dialysis Therapy. JSDT annual reports. Accessed 30 Jan 2017.
  4. 4.
    Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53(6):982–92.CrossRefGoogle Scholar
  5. 5.
    Imai E, Horio M, Iseki K, et al. Prevalence of chronic kidney disease (CKD) in the Japanese general population predicted by MDRD equation modified by a Japanese coefficient. Clin Exp Nephrol. 2007;11:156–63.CrossRefGoogle Scholar
  6. 6.
    Imai E, Horio M, Yamagata K, et al. Slower decline of glomerular filtration rate in the Japanese general population: a longitudinal 10-year follow-up study. Hypertens Res. 2008;31(3):433–41.CrossRefGoogle Scholar
  7. 7.
    Watanabe Y, Yamagata K, Nishi S, et al. JSDT clinical guideline for “hemodialysis initiation for maintenance hemodialysis”. Ther Apher Dial. 2015;19(Suppl 1):93–107.CrossRefGoogle Scholar
  8. 8.
    Yamagata K, Ishida K, Sairenchi 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.CrossRefGoogle Scholar
  9. 9.
    Tozawa M, Iseki K, Iseki C, et al. Influence of smoking and obesity on the development of proteinuria. Kidney Int. 2002;62:956–62.CrossRefGoogle Scholar
  10. 10.
    Okusa MD, Davenport A. Reading between the (guide) lines—the KDIGO practice guideline on acute kidney injury in the individual patient. Kidney Int. 2014;85(1):39–48.CrossRefGoogle Scholar
  11. 11.
    James MT, Pannu N, Hemmelgarn BR, et al. Derivation and external validation of prediction models for advanced chronic kidney disease following acute kidney injury. JAMA. 2017;318(18):1787–97.CrossRefGoogle Scholar
  12. 12.
    Yokoyama H, Sugiyama H, Sato H, et al. Renal disease in the elderly and the very elderly Japanese: analysis of the Japan Renal Biopsy Registry (J-RBR). Clin Exp Nephrol. 2012;16:903–20.CrossRefGoogle Scholar
  13. 13.
    Tanaka S, Ninomiya T, Katafuchi R, et al. Secular trends in the incidence of end-stage renal disease and its risk factors in Japanese patients with immunoglobulin A nephropathy. Nephrol Dial Transplant. 2018;33(6):963–71.CrossRefGoogle Scholar
  14. 14.
    Iseki K, Iseki C, Ikemiya Y, Fukiyama K. Risk of developing end-stage renal disease in a cohort of mass screening. Kidney Int. 1996;49:800–5.CrossRefGoogle Scholar
  15. 15.
    Iseki K. Factors influencing development of end-stage renal disease. Clin Exp Nephrol. 2005;9:5–14.CrossRefGoogle Scholar
  16. 16.
    Iseki K. Proteinuria as a predictor of rapid eGFR decline. Nat Rev Nephrol. 2013;9:570–1.CrossRefGoogle Scholar
  17. 17.
    Hallan SI, Matsushita K, Sang Y, et al. Age and association of kidney measures with mortality and end-stage renal disease. JAMA. 2012;308(22):2349–60.CrossRefGoogle Scholar
  18. 18.
    Iseki K, Shinzato T, Nagura Y, Akiba T. Factors influencing long-term survival in patients on chronic dialysis. Clin Exp Nephrol. 2004;8:89–97.PubMedGoogle Scholar
  19. 19.
    Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int. 2003;63:793–808.CrossRefGoogle Scholar
  20. 20.
    Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150.CrossRefGoogle Scholar
  21. 21.
    Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012;2:337–414.CrossRefGoogle Scholar
  22. 22.
    Yamagata K, Makino H, Iseki K, et al. Effect of behavior modification on outcome in early- to moderate-stage chronic kidney disease: a cluster-randomized trial. PLoS One. 2016;11(3):e0151422.CrossRefGoogle Scholar
  23. 23.
    Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years a randomized clinical trial. JAMA. 2016;315(24):2673–82.CrossRefGoogle Scholar
  24. 24.
    Chobanian IV. SPRINT results in older patients—how low to go? JAMA. 2016;315(24):2669–70.CrossRefGoogle Scholar
  25. 25.
    Sexton DJ, Canney M, O’Connell MDL, et al. Injurious falls and syncope in older community-dwelling adults meeting inclusion criteria for SPRINT. JAMA Intern Med. 2017;177(9):1385–7.CrossRefGoogle Scholar
  26. 26.
    Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998;339:584–90.CrossRefGoogle Scholar
  27. 27.
    Palmer SC, Navaneethan SD, Craig JC, et al. Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease. Ann Intern Med. 2010;153:23–33.CrossRefGoogle Scholar
  28. 28.
    Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012;2:279–335.CrossRefGoogle Scholar
  29. 29.
    Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2009;113:S1–130.Google Scholar
  30. 30.
    Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of CKD-MBD. Kidney Int Suppl. 2017;7:1–59.CrossRefGoogle Scholar
  31. 31.
    Ikizler TA, Cano NJ, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int. 2013;84(6):1096–107.CrossRefGoogle Scholar
  32. 32.
    Lentine KL, Kasiske BL, Levey AS, et al. KDIGO clinical practice guideline on the evaluation and care of living kidney donors. Transplantation. 2017;101(8S Suppl 1):S1–S109.PubMedGoogle Scholar
  33. 33.
    Kanda E, Usui T, Kashihara N, et al. Importance of glomerular filtration rate change as surrogate endpoint for the future incidence of end-stage renal disease in general Japanese population: community-based cohort study. Clin Exp Nephrol. 2018;22(2):318–27.CrossRefGoogle Scholar
  34. 34.
    Usui T, Kanda E, Iseki C, et al. Observation period for changes in proteinuria and risk prediction of end-stage renal disease in general population. Nephrology. 2018 (in press).Google Scholar
  35. 35.
    Strippoli GFM, Craig JC, Schena FP. The number, quality, and coverage of randomized controlled trials in nephrology. JASN. 2004;15:411–9.CrossRefGoogle Scholar
  36. 36.
    Iseki K, Asahi K, Moriyama T, et al. Risk factor profiles based on eGFR and dipstick proteinuria: analysis of the participants of the specific health check and guidance system in Japan 2008. Clin Exp Nephrol. 2012;16:244–9.CrossRefGoogle Scholar
  37. 37.
    Iseki K, Asahi K, Yamagata K, et al. Mortality risk among screened subjects of the specific health check and guidance program in Japan 2008–2012. Clin Exp Nephrol. 2017;21:978–85.CrossRefGoogle Scholar
  38. 38.
    Wakasugi M, Kazama JJ, Narita I, et al. Associations between combined lifestyle factors and non-restorative sleep in Japan: a cross-sectional study based on a Japanese health database. PLoS One. 2014;9(9):e108718.CrossRefGoogle Scholar
  39. 39.
    Wakasugi M, Kazama JJ, Narita I, et al. Association between overall lifestyle changes and incidence of proteinuria: a population-based, cohort study. Intern Med. 2017;56(12):1475–84.CrossRefGoogle Scholar
  40. 40.
    Kondo M, Yamagata K, Hoshi SL, et al. Cost-effectiveness of chronic kidney disease mass screening test in Japan. Clin Exp Nephrol. 2012;16:279–91.CrossRefGoogle Scholar
  41. 41.
    Kondo M, Yamagata K, Hoshi SL, et al. Budget impact analysis of chronic kidney disease mass screening test in Japan. Clin Exp Nephrol. 2014;18(6):885–91.CrossRefGoogle Scholar
  42. 42.
    Iseki K, Iseki C, Kurahashi I, Watanabe T. Effect of glomerular filtration rate and proteinuria on medical cost among screened subjects. Clin Exp Nephrol. 2013;17:372–8.CrossRefGoogle Scholar
  43. 43.
    Ohara T, Hata J, Yoshida D, et al. Trends in dementia prevalence, incidence, and survival rate in a Japanese community. Neurology. 2017;88(20):1925–32.CrossRefGoogle Scholar
  44. 44.
    Watanabe Y, Hirakata H, Okada K, et al. Proposal for the shared decision-making process regarding initiation and continuation of maintenance hemodialysis. Ther Apher Dial. 2015;19(Suppl 1):108–17.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Kunitoshi Iseki
    • 1
  1. 1.Clinical Research Support Center, Nakamura ClinicOkinawaJapan

Personalised recommendations