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Effects of nicorandil on the reduction of BNP levels in patients with chronic kidney disease

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Abstract

Background

Patients with chronic kidney disease (CKD) still frequently experience cardiovascular events despite recent progress in treatment. We examined whether nicorandil, a hybrid nitrate and adenosine triphosphate-sensitive potassium channel opener, could improve a biomarker and physiological markers of cardiovascular events.

Methods

Patients with advanced stage CKD (stage III–V with or without peritoneal dialysis) were included in this trial if they were considered at high risk for cardiovascular events [past history of cardiovascular diseases, past history of coronary angiography, presence of endothelial dysfunction measured by reactive hyperemia peripheral arterial tonometry, and presence of high brain natriuretic peptide (BNP) values]. Patients were randomly assigned to be treated with or without oral nicorandil, 15 mg/day. BNP values and endothelial function (augmentation index, pulse wave velocity, and reactive hyperemia peripheral arterial tonometry) before and 1 month after the initiation of the trial were assessed.

Results

Nineteen patients (15 men, 4 women) with a mean age of 61 ± 10 (SD) years were included. The median baseline BNP value was 75.3 (interquartile range, 32.1–138.8) pg/ml, and the BNP level was significantly reduced in the nicorandil group (P < 0.05). Regression analysis demonstrated that only the use of nicorandil is related to a decrease of BNP levels [standardized β coefficient, −75.1 (95% CI, −19.7 to −130.6), P = 0.01]. There were no significant changes in the rest of the parameters in the nicorandil group in comparison to the control group. The change in BNP levels was correlated with changes in the augmentation index (P < 0.01) and central pulse pressure (P = 0.03).

Conclusions

Nicorandil treatment may reduce the level of BNP by reducing the central blood pressure in CKD patients.

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References

  1. 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.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  PubMed  CAS  Google Scholar 

  3. Hayashi T, Obi Y, Kimura T, Iio KI, Sumitsuji S, Takeda Y, et al. Cardiac troponin T predicts occult coronary artery stenosis in patients with chronic kidney disease at the start of renal replacement therapy. Nephrol Dial Transpl. 2008;23:2936–42.

    Article  CAS  Google Scholar 

  4. Joki N, Hase H, Nakamura R, Yamaguchi T. Onset of coronary artery disease prior to initiation of haemodialysis in patients with end-stage renal disease. Nephrol Dial Transpl. 1997;12:718–23.

    Article  CAS  Google Scholar 

  5. Al Suwaidi J, Reddan DN, Williams K, Pieper KS, Harrington RA, Califf RM, et al. Prognostic implications of abnormalities in renal function in patients with acute coronary syndromes. Circulation. 2002;106:974–80.

    Article  PubMed  Google Scholar 

  6. Sadeghi HM, Stone GW, Grines CL, Mehran R, Dixon SR, Lansky AJ, et al. Impact of renal insufficiency in patients undergoing primary angioplasty for acute myocardial infarction. Circulation. 2003;108:2769–75.

    Article  PubMed  Google Scholar 

  7. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2):S1–266.

    Article  Google Scholar 

  8. National Kidney Foundation. K/DOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis. 2006;47(5):S1–149.

    Google Scholar 

  9. Kimura T, Obi Y, Yasuda K, Sasaki KI, Takeda Y, Nagai Y, et al. Effects of chronic kidney disease and post-angiographic acute kidney injury on long-term prognosis after coronary artery angiography. Nephrol Dial Transplant. 2010.

  10. Obi Y, Kimura T, Nagasawa Y, Yamamoto R, Yasuda K, Sasaki K, et al. Impact of age and overt proteinuria on outcomes of stage 3 to 5 chronic kidney disease in a referred cohort. Clin J Am Soc Nephrol. 2010;5:1558–65.

    Article  PubMed  Google Scholar 

  11. Zoccali C, Mallamaci F, Benedetto FA, Tripepi G, Parlongo S, Cataliotti A, et al. Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients. J Am Soc Nephrol. 2001;12:1508–15.

    PubMed  CAS  Google Scholar 

  12. Zoccali C, Mallamaci F. A green light for troponin T in the cardiovascular risk stratification of continuous ambulatory peritoneal dialysis patients? Kidney Int. 2006;70:408–10.

    Article  PubMed  CAS  Google Scholar 

  13. Yasuda K, Kimura T, Obi Y, Sasaki K, Hatanaka M, Isaka Y, et al. Plasma B-type natriuretic peptide level predicts the renal outcome in patients with chronic kidney disease. Nippon Jinzo Gakkai Shi. 2010;52:1007–14.

    PubMed  CAS  Google Scholar 

  14. Ohya Y, Iseki K, Iseki C, Miyagi T, Kinjo K, Takishita S. Increased pulse wave velocity is associated with low creatinine clearance and proteinuria in a screened cohort. Am J Kidney Dis. 2006;47:790–7.

    Article  PubMed  CAS  Google Scholar 

  15. Andrade J, Er L, Ignaszewski A, Levin A. Exploration of association of 1,25-OH2D3 with augmentation index, a composite measure of arterial stiffness. Clin J Am Soc Nephrol. 2008.

  16. Hogas SM, Voroneanu L, Serban DN, Segall L, Hogas MM, Serban IL, et al. Methods and potential biomarkers for the evaluation of endothelial dysfunction in chronic kidney disease: a critical approach. J Am Soc Hypertens. 2010;4:116–27.

    Article  PubMed  CAS  Google Scholar 

  17. Taira N. Nicorandil as a hybrid between nitrates and potassium channel activators. Am J Cardiol. 1989;63:18J–24J.

    Article  PubMed  CAS  Google Scholar 

  18. Kukovetz WR, Holzmann S, Braida C, Poch G. Dual mechanism of the relaxing effect of nicorandil by stimulation of cyclic GMP formation and by hyperpolarization. J Cardiovasc Pharmacol. 1991;17:627–33.

    Article  PubMed  CAS  Google Scholar 

  19. IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the impact of nicorandil in Angina (IONA) randomised trial. Lancet. 2002;359:1269–75.

    Article  Google Scholar 

  20. Nishimura M, Tokoro T, Nishida M, Hashimoto T, Kobayashi H, Imai R, et al. Oral nicorandil to reduce cardiac death after coronary revascularization in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2009.

  21. Sekiya M, Sato M, Funada J, Ohtani T, Akutsu H, Watanabe K. Effects of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis. J Cardiovasc Pharmacol. 2005;46:63–7.

    Article  PubMed  CAS  Google Scholar 

  22. Ishibashi Y, Takahashi N, Tokumaru A, Karino K, Sugamori T, Sakane T, et al. Effects of long-term nicorandil administration on endothelial function, inflammation, and oxidative stress in patients without coronary artery disease. J Cardiovasc Pharmacol. 2008;51:311–6.

    Article  PubMed  CAS  Google Scholar 

  23. Lee TM, Su SF, Chou TF, Lee YT, Tsai CH. Loss of preconditioning by attenuated activation of myocardial ATP-sensitive potassium channels in elderly patients undergoing coronary angioplasty. Circulation. 2002;105:334–40.

    Article  PubMed  CAS  Google Scholar 

  24. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.

    Article  PubMed  CAS  Google Scholar 

  25. Hashimoto J, Imai Y, O’Rourke MF. Indices of pulse wave analysis are better predictors of left ventricular mass reduction than cuff pressure. Am J Hypertens. 2007;20:378–84.

    Article  PubMed  Google Scholar 

  26. Takazawa K, Kobayashi H, Shindo N, Tanaka N, Yamashina A. Relationship between radial and central arterial pulse wave and evaluation of central aortic pressure using the radial arterial pulse wave. Hypertens Res. 2007;30:219–28.

    Article  PubMed  Google Scholar 

  27. Bonetti PO, Barsness GW, Keelan PC, Schnell TI, Pumper GM, Kuvin JT, et al. Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease. J Am Coll Cardiol. 2003;41:1761–8.

    Article  PubMed  Google Scholar 

  28. Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Kuvin JT, Lerman A. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004;44:2137–41.

    Article  PubMed  Google Scholar 

  29. Matsuzawa Y, Sugiyama S, Sugamura K, Nozaki T, Ohba K, Konishi M, et al. Digital assessment of endothelial function and ischemic heart disease in women. J Am Coll Cardiol. 2010;55:1688–96.

    Article  PubMed  Google Scholar 

  30. Tagore R, Ling LH, Yang H, Daw HY, Chan YH, Sethi SK. Natriuretic peptides in chronic kidney disease. Clin J Am Soc Nephrol. 2008.

  31. Vickery S, Price CP, John RI, Abbas NA, Webb MC, Kempson ME, et al. B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy. Am J Kidney Dis. 2005;46:610–20.

    Article  PubMed  CAS  Google Scholar 

  32. Vanderheyden M, Bartunek J, Goethals M. Brain and other natriuretic peptides: molecular aspects. Eur J Heart Fail. 2004;6:261–8.

    Article  PubMed  CAS  Google Scholar 

  33. Vesely DL. Natriuretic peptides and acute renal failure. Am J Physiol Renal Physiol. 2003;285:F167–77.

    PubMed  CAS  Google Scholar 

  34. Maeder MT, Mariani JA, Kaye DM. Hemodynamic determinants of myocardial B-type natriuretic peptide release: relative contributions of systolic and diastolic wall stress. Hypertension. 2010;56:682–9.

    Article  PubMed  CAS  Google Scholar 

  35. Cecelja M, Jiang B, McNeill K, Kato B, Ritter J, Spector T, et al. Increased wave reflection rather than central arterial stiffness is the main determinant of raised pulse pressure in women and relates to mismatch in arterial dimensions: a twin study. J Am Coll Cardiol. 2009;54:695–703.

    Article  PubMed  Google Scholar 

  36. Date T, Taniguchi I, Inada K, Matsuo S, Miyanaga S, Yamane T, et al. Nicorandil inhibits serum starvation-induced apoptosis in vascular endothelial cells. J Cardiovasc Pharmacol. 2005;46:721–6.

    Article  PubMed  CAS  Google Scholar 

  37. Hongo M, Mawatari E, Sakai A, Ruan Z, Koizumi T, Terasawa F, et al. Effects of nicorandil on monocrotaline-induced pulmonary arterial hypertension in rats. J Cardiovasc Pharmacol. 2005;46:452–8.

    Article  PubMed  CAS  Google Scholar 

  38. Horinaka S, Kobayashi N, Higashi T, Hara K, Hara S, Matsuoka H. Nicorandil enhances cardiac endothelial nitric oxide synthase expression via activation of adenosine triphosphate-sensitive K channel in rat. J Cardiovasc Pharmacol. 2001;38:200–10.

    Article  PubMed  CAS  Google Scholar 

  39. Teshima Y, Akao M, Baumgartner WA, Marban E. Nicorandil prevents oxidative stress-induced apoptosis in neurons by activating mitochondrial ATP-sensitive potassium channels. Brain Res. 2003;990:45–50.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, B6, 2-2 Yamada-oka, Suita, Osaka, 585-0871, Japan

    Tomonori Kimura, Harumi Kitamura, Kazunori Inoue, Noritaka Kawada, Isao Matsui, Yasuyuki Nagasawa, Yoshitsugu Obi, Maki Shinzawa, Takayuki Hamono, Hiromi Rakugi & Yoshitaka Isaka

  2. Department of Cardiology, Osaka University Graduate School of Medicine, B6, 2-2 Yamada-oka, Suita, Osaka, 585-0871, Japan

    Yasuhiko Sakata

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  1. Tomonori Kimura
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  2. Harumi Kitamura
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Correspondence to Yoshitaka Isaka.

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Kimura, T., Kitamura, H., Inoue, K. et al. Effects of nicorandil on the reduction of BNP levels in patients with chronic kidney disease. Clin Exp Nephrol 15, 854–860 (2011). https://doi.org/10.1007/s10157-011-0522-1

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  • DOI: https://doi.org/10.1007/s10157-011-0522-1

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