Clinical and Experimental Nephrology

, Volume 14, Issue 4, pp 333–339 | Cite as

Different clinical outcomes for cardiovascular events and mortality in chronic kidney disease according to underlying renal disease: the Gonryo study

  • Masaaki NakayamaEmail author
  • Toshinobu Sato
  • Hiroshi Sato
  • Yuji Yamaguchi
  • Katsuya Obara
  • Isao Kurihara
  • Kazuto Sato
  • Osamu Hotta
  • Jin Seino
  • Masahiro Miyata
  • Kazuhisa Takeuchi
  • Kenji Nakayama
  • Masato Matsushima
  • Tetsuya Otaka
  • Yasumichi Kinoshita
  • Yoshio Taguma
  • Sadayoshi Ito
Original Article



Chronic kidney disease (CKD) can result from a wide variety of diseases, but whether clinical outcomes differ in the same CKD stages according to the underlying renal disease remains unclear. Clarification of this issue is important for stratifying risk of cardiovascular disease (CVD) and death in patients before dialysis.

Patients and methods

The study comprised 2,692 patients recruited from 11 outpatient nephrology clinics, classified by underlying disease of primary renal disease (PRD) (n = 1,306), hypertensive nephropathy (HN) (n = 458), diabetic nephropathy (DN) (n = 283), or other nephropathies (ON) (n = 645). Risks of events such as ischemic heart disease, congestive heart failure, stroke, and all-cause mortality within 12 months were examined by logistic regression analysis in each group.


During the 12-months’ observation from recruitment, 200 cases were lost to follow-up, and 113 cases were introduced to chronic dialysis therapy. A total of 69 CVD events occurred (stroke in 27 cases), and 24 patients died. In total, increased odds ratios (OR) for the events by CKD stage (cf. CKD1 + 2: unadjusted) were CKD3, 1.29 [95% confidence interval (CI), 0.70–2.17]; CKD4, 2.73 (1.55–4.83); and CKD5, 4.66 (2.63–8.23). Regarding events in respective groups, no significant differences were seen by CKD stage except for the group with HN, but significant differences were seen by underlying diseases (cf. PRD: adjusted for confounding factors, including estimated glomerular filtration rate): HN, 2.57 (1.09–6.04); DN, 12.21 (3.90–38.20); and ON, 4.14 (1.93–8.89).


Risk of CVD and mortality due to CKD needs to be stratified according to the underlying renal diseases.


Chronic kidney disease Cardiovascular disease Nephritis Hypertension Diabetic nephropathy 



This study was supported by Grant from Astellas Pharma Inc. The authors express their special thanks to Mrs. Makiko Nakayama and Mr. Jun Sakaino for their devoted assistance to the study projects. Study contributors: Akira Sugiura (Osaki Citizen Hospital), Tasuku Nagasawa, Noriko Miyazawa, Takuma Hosoya (Tohoku University School of Medicine), Naoki Akiu (Sendai City Hospital), Hiroo Noshiro, Mariko Miyazaki, Kazuyuki Suzuki, Mitsuhiro Sato, Norio Ieiri, Yoshinori Tsuchiya, Kozo Sato, Tomoyoshi Kimura, Aki Ishida (Sendai Shakaihoken Hospital).

Conflict of interest statement



  1. 1.
    Manjunath G, Tighiouart H, Ibrahim H, MacLeod B, Salem DN, Griffith JL, et al. Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community. J Am Coll Cardiol. 2003;41:47–55.CrossRefPubMedGoogle Scholar
  2. 2.
    Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med. 2004;164:659–63.CrossRefPubMedGoogle Scholar
  3. 3.
    AS GO, Chertow GM, Fan D, McCulloch CE, Hsu C. Chronic kidney disease and the risks of death, cardiovascular events, and the hospitalization. New Engl J Med. 2004;351:1296–305.CrossRefGoogle Scholar
  4. 4.
    Ninomiya T, Kiyohara Y, Kubo M, Tanizaki Y, Doi Y, Okubo K, Wakugawa Y, Hata J, Oishi Y, Shikata K, Yonemoto K, Hirakata H, Iida M. Choronic kidney disease and cardiovascular disease in a general Japanese population: the Hisayama Study. Kidney Int. 2005;68:228–36.CrossRefPubMedGoogle Scholar
  5. 5.
    Irie F, Sairenchi T, Fukasawa N, Yamagishi K, Ikehara S, Kanashiki M, Saito Y, Ota H, Nose T. The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population. Kidney Int. 2006;69:1264–71.CrossRefPubMedGoogle Scholar
  6. 6.
    Nakayama M, Metoki H, Terawaki H, Ohkubo T, Kikuya M, Sato T, et al. Kidney dysfunction as a risk factor for first symptomatic stroke events in a general Japanese population—the Ohasama study. Nephrol Dial Transplant. 2007;22(7):1910–5.CrossRefPubMedGoogle Scholar
  7. 7.
    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
  8. 8.
    Kidney Disease Outcome Quality Initiative. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(Suppl 2):S1–246.Google Scholar
  9. 9.
    Wattanakit K, Coresh J, Muntner P, Marsh J, Folsom AR. Cardiovascular risk among adults with chronic kidney disease, with or without prior myocardial infarction. J Am Coll Cardiol. 2006;48(6):1183–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Ahmed A, Rich MW, Sanders PW, Perry GJ, Bakris GL, Zile MR, et al. Chronic kidney disease associated mortality in diastolic versus systolic heart failure: a propensity matched study. Am J Cardiol. 2007;99(3):393–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Kokubo Y, Nakamura S, Okamura T, Yoshimasa Y, Makino H, Watanabe M, et al. Relationship between blood pressure category and incidence of stroke and myocardial infarction in an urban Japanese population with and without chronic kidney disease: the Suita Study. Stroke. 2009;40(8):2674–9. (Epub 2009 May 28).CrossRefPubMedGoogle Scholar
  12. 12.
    So WY, Kong AP, Ma RC, Ozaki R, Szeto CC, Chan NN, et al. Glomerular filtration rate, cardiorenal end points, and all-cause mortality in type 2 diabetic patients. Diabetes Care. 2006;29(9):2046–52.CrossRefPubMedGoogle Scholar
  13. 13.
    Roderick PJ, Atkins RJ, Smeeth L, Mylne A, Nitsch DD, Hubbard RB, Bulpitt CJ, Fletcher AE. CKD and mortality risk in older people: a community-based population study in the United Kingdom. Am J Kidney Dis. 2009;53(6):950–60.CrossRefPubMedGoogle Scholar
  14. 14.
    Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt KU, et al. CKD as a global public health problem: approaches and initiatives—a position statement from Kidney disease Improving Global Outcomes. Kidney Int. 2007;72:247–59.CrossRefPubMedGoogle Scholar
  15. 15.
    Islam TM, Fox CS, Mann D, Muntner P. Age-related associations of hypertension and diabetes mellitus with chronic kidney disease. BMC Nephrol. 2009;10:17. doi: 10.1186/1471-2369-10-17.CrossRefPubMedGoogle Scholar
  16. 16.
    Tsimihodimos V, Dounousi E, Siamopoulos KC. Dyslipidemia in chronic kidney disease: an approach to pathogenesis and treatment. Am J Nephrol. 2008;28(6):958–73.CrossRefPubMedGoogle Scholar
  17. 17.
    Deegens JK, Wetzels JF. Membranous nephropathy in the older adult: epidemiology, diagnosis and management. Drugs Aging. 2007;24(9):717–32.CrossRefPubMedGoogle Scholar
  18. 18.
    Glassock RJ. Prophylactic anticoagulation in nephrotic syndrome: a clinical conundrum. J Am Soc Nephrol. 2007;18(8):2221–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammaritano L, Simantov R, Crow MK, Schwartz JE, Paget SA, Devereux RB, Salmon JE. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med. 2003;349(25):2399–406.CrossRefPubMedGoogle Scholar
  20. 20.
    Lechner BL, Bockenhauer D, Iragorri S, Kennedy TL, Siegel NJ. The risk of cardiovascular disease in adults who have had childhood nephrotic syndrome. Pediatr Nephrol. 2004;19(7):744–8. (Epub 2004 Apr 15).CrossRefPubMedGoogle Scholar
  21. 21.
    Morgan MD, Turnbull J, Selamet U, Kaur-Hayer M, Nightingale P, Ferro CJ, et al. Increased incidence of cardiovascular events in patients with antineutrophil cytoplasmic antibody-associated vasculitides: a matched-pair cohort study. Arthritis Rheum. 2009;60(11):3493–500.CrossRefPubMedGoogle Scholar
  22. 22.
    National Institue of Neurological Disorders and Stroke Ad Hoc Committee. Classification of cerebrovascular disease. Stroke. 1990;21:637–76.Google Scholar
  23. 23.
    Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53(6):982–92.CrossRefPubMedGoogle Scholar
  24. 24.
    Takahashi M, Fukuda Y, Iwata S. Fundamental evaluation and efficacy for protein to creatinine ratio by ATLAS kit cartridge PRO12 using automatic urine analyzer Clinitek ATLAS XL. Igaku To Yakugaku. 2002;48:727–35. (in Japanese).Google Scholar
  25. 25.
    Yamamoto S, Kon V. Mechanisms for increased cardiovascular disease in chronic kidney dysfunction. Curr Opin Nephrol Hypertens. 2009;18(3):181–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol. 2005;16(2):520–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Honda H, Qureshi AR, Heimbürger O, Barany P, Wang K, Pecoits-Filho R, et al. Serum albumin, C-reactive protein, interleukin 6, and fetuin a as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis. 2006;47(1):139–48.CrossRefPubMedGoogle Scholar
  28. 28.
    Chan DT, Irish AB, Dogra GK, Watts GF. Dyslipidaemia and cardiorenal disease: mechanisms, therapeutic opportunities and clinical trials. Atherosclerosis. 2008;196(2):823–34.CrossRefPubMedGoogle Scholar
  29. 29.
    Kazory A, Ross EA. Anemia: the point of convergence or divergence for kidney disease and heart failure? J Am Coll Cardiol. 2009;53(8):639–47.CrossRefPubMedGoogle Scholar
  30. 30.
    Himmelfarb J, Stenvinkel P, Ikizler TA, Hakim RM. The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int. 2002;62:1524–38.CrossRefPubMedGoogle Scholar
  31. 31.
    Vaziri ND, Rodriguez-Iturbe B. Mechanisms of disease: oxidative stress and inflammation in the pathogenesis of hypertension. Nature Clin practice. 2006;2:582–93.CrossRefGoogle Scholar
  32. 32.
    Ravani P, Tripepi G, Malberti F, Testa S, Mallamaci F, Zoccali C. Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: a competing risks modeling approach. J Am Soc Nephrol. 2005;16(8):2449–55.CrossRefPubMedGoogle Scholar
  33. 33.
    Cheng J, Zhang X, Zhang W, He Q, Tao X, Chen J. Efficacy and safety of glucocorticoids therapy for IgA nephropathy: a meta-analysis of randomoized controlled trials. Am J Nephrol. 2009;30(4):315–22.CrossRefPubMedGoogle Scholar
  34. 34.
    Sawada T, Yamada H, Dahlöf B, Matsubara H. KYOTO HEART Study Group. Effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high cardiovascular risks: KYOTO HEART Study. Eur Heart J. 2009;30(20):2461–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Wilson AC, Mitsnefes MM. Cardiovascular disease in CKD in children: update on risk factors, risk assessment, and management. Am J Kidney Dis. 2009;54(2):345–60.CrossRefPubMedGoogle Scholar
  36. 36.
    Lilien MR, Groothoff JW. Cardiovascular disease in children with CKD or ESRD. Nat Rev Nephrol. 2009;5(4):229–35.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2010

Authors and Affiliations

  • Masaaki Nakayama
    • 1
    Email author
  • Toshinobu Sato
    • 2
  • Hiroshi Sato
    • 1
  • Yuji Yamaguchi
    • 3
  • Katsuya Obara
    • 4
  • Isao Kurihara
    • 5
  • Kazuto Sato
    • 6
  • Osamu Hotta
    • 2
  • Jin Seino
    • 7
  • Masahiro Miyata
    • 8
  • Kazuhisa Takeuchi
    • 9
  • Kenji Nakayama
    • 10
  • Masato Matsushima
    • 11
  • Tetsuya Otaka
    • 12
  • Yasumichi Kinoshita
    • 6
  • Yoshio Taguma
    • 2
  • Sadayoshi Ito
    • 1
  1. 1.Tohoku University Graduate School of MedicineSendaiJapan
  2. 2.Sendai Shakaihoken HospitalSendaiJapan
  3. 3.Japanese Red Cross Sendai HospitalSendaiJapan
  4. 4.Tohoku Kosai HospitalSendaiJapan
  5. 5.Tohoku Kosai Miyagino HospitalSendaiJapan
  6. 6.Japanese Red Cross Ishinomaki HospitalIshinomakiJapan
  7. 7.Sendai Medical CenterSendaiJapan
  8. 8.Osaki Citizen HospitalOsakiJapan
  9. 9.Koujinkai Central Hemodialysis ClinicSendaiJapan
  10. 10.Sendai City HospitalSendaiJapan
  11. 11.The Jikei University School of MedicineTokyoJapan
  12. 12.Katta General HospitalShiroishiJapan

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