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The relationship of plasma ADMA levels with cardiac functions and metabolic parameters in peritoneal dialysis patients

Clinical and Experimental Nephrology volume 17, pages 431–436 (2013)Cite this article

Abstract

Background

Asymmetric dimethylarginine (ADMA) is accepted as a risk factor for coronary artery disease because it causes endothelial dysfunction and vasospasm. In this study we aimed to investigate the relationship between ADMA levels and echocardiographic and metabolic parameters in peritoneal dialysis (PD) patients.

Methods

This is a cross-sectional study in which PD patients aged 18–80, with at least 3-month duration of dialysis and without active cardiac, infectious or malignant diseases, and clinically evident hypervolemia, were included. ADMA levels and echocardiographic parameters were recorded.

Results

Of the 55 patients included, the mean age was 53 ± 15 years. Mean ADMA level was 81.9 ± 48.0 μmol/l. The variables found to be positively correlated with ADMA levels were weight, body surface area, body mass index (BMI), serum glucose level, uric acid and sodium levels, ultrafiltration volume, left atrium diameter, intraventricular end-systolic diameter and intraventricular end-diastolic diameter. The parathyroid hormone, dialysate K t/V and ejection fraction were negatively correlated with ADMA levels. ADMA levels were higher in patients with hypertension. With multivariate analysis, gender, BMI and use of acetyl salicylic acid were found to be the independent variables determining ADMA levels.

Conclusion

The correlation of ADMA with BMI, gender, hypertension, left atrium diameter, intraventricular end-systolic diameter and intraventricular end-diastolic diameter led to the idea that ADMA may aid in the determination of cardiovascular disease risk in PD patients.

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References

  1. Miller LM, Sood MM, Sood AR, Reslerova M, Komenda P, Rigatto C, et al. Cardiovascular disease in end-stage renal disease: the challenge of assessing and managing cardiac disease in dialysis patients. Int Urol Nephrol. 2010;42:1007–14.

    PubMed  Article  CAS  Google Scholar 

  2. Moncada S, Palmer RMJ, Higgs EA. Biosynthesis of nitric oxide from l-arginine: a pathway for the regulation of cell function and communication. Biochem Pharmacol. 1989;38:1709–15.

    PubMed  Article  CAS  Google Scholar 

  3. Yılmaz MI, Sonmez A, Saglam M, Qureshi AR, Carrero JJ, Caglar K, et al. ADMA levels correlate with proteinuria, secondary amyloidosis, and endothelial dysfunction. J Am Soc Nephrol. 2008;19(2):388–95.

    PubMed  Article  Google Scholar 

  4. Fliser D, Kielstein JT, Haller H, Böger SMB. Asymmetric dimethylarginine: a cardiovascular risk factor in renal disease? Kidney Int. 2003;63(84):37–40.

    Article  Google Scholar 

  5. Faraci FM, Brian JE, Heistad DD. Response of cerebral blood vessels to an endogenous inhibitor of nitric oxide synthase. Am J Physiol. 1995;269:1522–7.

    Google Scholar 

  6. Çakir E, Özcan O, Yaman H, Akgul EO, Bilgi C, Erbil MK, et al. Elevated plasma concentration of asymmetric dimethylarginine that is reduced by single dose testosterone administration in idiopathic hypogonadotropic hypogonadism patients. J Clin Endocrinol Metab. 2004;90(3):1651–4.

    PubMed  Article  Google Scholar 

  7. Avcı E, Coskun S, Çakır E, Kurt Y, Ozgur Akgul E, Bilgi C. Relations between concentrations of asymmetric dimethylarginine and neopterin as potential risk factors for cardiovascular diseases in haemodialysis-treated patients. Ren Fail. 2008;30(8):784–90.

    PubMed  Article  Google Scholar 

  8. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation. 1977;55:613–8.

    PubMed  Article  CAS  Google Scholar 

  9. Stenvinkel P, Carrero JJ, Axelsson J, Lindholm B, Heimbürger O, Massy Z. Emerging biomarkers for evaluating cardiovascular risk in the chronic kidney disease patient: how do new pieces fit into the uremic puzzle? Clin J Am Soc Nephrol. 2008;3:505–21.

    PubMed  Article  CAS  Google Scholar 

  10. K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis. 2005;45:1–153.

    Google Scholar 

  11. Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP. Novel mechanism for endothelial dysfunction. Dysregulation of dimethylarginine dimethylaminohydrolase. Circulation. 1999;99(24):3092–5.

    PubMed  Article  CAS  Google Scholar 

  12. Böger RH, Bode-Böger SM, Szuba A, Tsao PS, Chan JR, Tanqphao O, et al. Asymmetric dimethylarginine: a novel risk factor for endothelial dysfunction. Its role in hypercholesterolemia. Circulation. 1998;98:1842–7.

    PubMed  Article  Google Scholar 

  13. Fleck C, Schweitzer F, Karge E, Busch M, Stein G. Serum concentration of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in patients with chronic kidney diseases. Clin Chim Acta. 2003;336:1–12.

    PubMed  Article  CAS  Google Scholar 

  14. Kielstein JT, Böger RH, Bode-Böger SM, Schaffer J, Barbey M, Koch KM, et al. Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: relationship to treatment method and atherosclerotic disease. J Am Soc Nephrol. 1999;10:594–600.

    PubMed  CAS  Google Scholar 

  15. Ebinç FA, Erten Y, Ebinç H, Paşaoğlu H, Demirtaş C, Taçoy G, et al. The relationship among asymmetric dimethylarginine (ADMA) levels, residual renal function, and left ventricular hypertrophy in continuous ambulatory peritoneal dialysis patients. Ren Fail. 2008;30(4):401–6.

    PubMed  Article  Google Scholar 

  16. Perticone F, Sciacqua A, Maio R, Perticone M, Maas R, Boger RH, et al. Asymmetric dimethylarginine, l-arginine, and endothelial dysfunction in essential hypertension. J Am Coll Cardiol. 2005;46(3):518–23.

    PubMed  Article  CAS  Google Scholar 

  17. Lentz SR, Rodionov RN, Dayal S. Hyperhomocysteinemia, endothelial dysfunction, and cardiovascular risk: the potential role of ADMA. Atheroscler Suppl. 2003;4:61–5.

    PubMed  Article  CAS  Google Scholar 

  18. Zoccali C, Mallamaci F, Tripepi G. Novel cardiovascular risk factors in end-stage renal disease. J Am Soc Nephrol. 2004;15:77–80.

    Article  Google Scholar 

  19. Hodis HN, Mack WJ, Labree L, Selzer RH, Liu CR, Liu CH, et al. The role of carotid arterial intima-media thickness in predicting clinical coronary events. Ann Intern Med. 1998;128:262–9.

    PubMed  Article  CAS  Google Scholar 

  20. Mallamaci F, Tripepi G, Cutrupi S, Malatino LS, Zoccali C. Prognostic value of combined use of biomarkers of inflammation, endothelial dysfunction, and myocardiopathy in patients with ESRD. Kidney Int. 2005;67:2330–7.

    PubMed  Article  CAS  Google Scholar 

  21. Lin KY, Ito A, Asagami T, Adimoolam S, Kimoto M, Tsuji H, et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation. 2002;106:987–92.

    PubMed  Article  CAS  Google Scholar 

  22. Chan NN, Chan JC. Asymmetric dimethylarginine (ADMA): a potential link between endothelial dysfunction and cardiovascular diseases in insulin resistance syndrome? Diabetologia. 2002;45(12):1609–16.

    PubMed  Article  CAS  Google Scholar 

  23. Kryzuzanowska K, Mittermayer F, Kopp HP, Wolzt M, Scherthaner G. Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidly obese women. J Clin Endocrinol Metab. 2004;89:277–81.

    Google Scholar 

  24. Konukoglu D, Uzun H, Firtina S, Cigdem Arica P, Kocael A, Taskin M. Plasma adhesion and inflammation markers: asymmetrical dimethyl-l-arginine and secretory phospholipase A2 concentrations before and after laparoscopic gastric banding in morbidly obese patients. Obes Surg. 2007;17:672–8.

    PubMed  Article  Google Scholar 

  25. Eid HM, Arnesen H, Hjerkinn EM, Lyberg T, Seljeflot I. Relationship between obesity, smoking and the endogen nitric oxide synthase inhibitor, ADMA. Metabolism. 2004;53:1574–9.

    PubMed  Article  CAS  Google Scholar 

  26. McLaughlin T, Stühlinger M, Lamendola C, Abbasi F, Bialek J, Reaven GM, et al. Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss. J Clin Endocrinol Metab. 2006;91:1896–900.

    PubMed  Article  CAS  Google Scholar 

  27. Marliss EB, Chevalier S, Gougeon R, Morais JA, Lamarche M, Adeqoke OA, et al. Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover. Diabetologia. 2005;21:1–9.

    Google Scholar 

  28. Böger RH, Bode-Böger SM, Szuba A, Tsao PS, Chan JR, Tanqphao O, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation. 1998;98(18):1842–7.

    PubMed  Article  Google Scholar 

  29. Janatuinen T, Laaksonen R, Vesalainen R, Raitakari O, Lehtimaki T, Nuutila P, et al. Effect of lipid-lowering therapy with pravastatin on myocardial blood flow in young mildly hypercholesterolemic adults. J Cardiovasc Pharmacol. 2001;38(4):561–8.

    PubMed  Article  CAS  Google Scholar 

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Conflict of interest

The authors have declared that no conflict of interest exists.

Author information

Affiliations

  1. Department of Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey

    Savas Ozturk, Serhat Karadag, Meltem Gursu, Sami Uzun & Zeki Aydin

  2. Department of Internal Medicine, Haseki Training and Research Hospital, Istanbul, Turkey

    Metin Yegen & Baki Kumbasar

  3. Department of Cardiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey

    Ahmet Gurdal

  4. Department of Biochemistry, Haseki Training and Research Hospital, Istanbul, Turkey

    Macit Koldas

  5. Department of Nephrology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey

    Rumeyza Kazancioglu

  6. Nefroloji Klinigi, Haseki Egitim ve Arastirma Hastanesi, Fatih, Istanbul, Turkey

    Meltem Gursu

Authors
  1. Savas Ozturk
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  2. Serhat Karadag
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  4. Meltem Gursu
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  5. Sami Uzun
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  7. Ahmet Gurdal
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  10. Rumeyza Kazancioglu
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Correspondence to Meltem Gursu.

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Ozturk, S., Karadag, S., Yegen, M. et al. The relationship of plasma ADMA levels with cardiac functions and metabolic parameters in peritoneal dialysis patients. Clin Exp Nephrol 17, 431–436 (2013). https://doi.org/10.1007/s10157-012-0739-7

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  • DOI: https://doi.org/10.1007/s10157-012-0739-7

Keywords

  • Asymmetric dimethylarginine
  • Cardiovascular disease
  • Echocardiography
  • Peritoneal dialysis