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Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients

Year 2013, Volume: 10 Issue: 2, 90 - 95, 01.06.2013

Abstract

Cardiovascular diseases and endothelial disfunction are major causes of mortality in patients with end stage renal disease (ESRD). Treatment strategies like continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) have different effects on different parameters. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthase inhibitor and it has been reported to be a novel marker for the progression of chronic kidney disease (CKD). Homocysteine is believed to cause atherogenesis and thrombogenesis via endothelial damage, vascular smooth muscle proliferation and coagulation abnormalities. In previous studies, conflicting findings have been reported about the effect of HD and CAPD on oxidant and antioxidant systems. In this study, we aimed to investigate ADMA, homocysteine and C- reactive protein (CRP) levels in patients with ESRD having HD and CAPD treatment and healthy individuals. This study was performed on 44 (23M, 21F) CAPD patients, 26 (13M, 13F) HD patients and 29 (15M, 14F) age and sex matched healthy control subjects. The lipid profile, ADMA, homocysteine, arginine and CRP levels were measured. Serum ADMA, homocysteine and CRP levels of the ESRD patients were significantly higher, whereas serum arginine levels were significantly lower in both HD and CAPD patients compared to control subjects. No differences were found between serum ADMA, homocysteine and CRP levels of the CAPD and HD patients. Our results suggest that ADMA, homocysteine and CRP levels were increased in HD and CAPD patients compared to the control subjects. These findings suggest that ESRD patients are prone to inflammation, oxidative stress and endothelial dysfunction. We conclude that endothelial dysfunction, inflammation and oxidative stress are increased in dialysis patients and ADMA concentrations are not affected by the modality of dialysis treatment.

References

  • United States Renal Data System. VI. Causes of death in ESRD. Am J Kidney Dis 1999;34(2 Suppl 1):87-94.
  • Foly RN, Parfrey PS, Sarnak MJ. Clinical epiıdemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32:112-11ı9.
  • Guebre-Egziabher F, Fougue D Metabolic consequences of inflammation in kidney failure. Nephrologie 2003;24:383–6.
  • Mak RH, Cheung W Adipokines and gut hormones in end- stage renal disease. Perit Dial Int 2007;27(Suppl 2):298–302.
  • Galli F Protein damage and inflammation in uremia and dialysis patients. Nephrol Dial Transplant 2007;22(Suppl 5):20–36.
  • Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C. Oxidative stress in end-stage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant 2003;18:1272–80.
  • Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1994;329:2002–12.
  • Ueda S, Yamagishi S, Matsumoto Y, et al. Involvement of asymmetric dimethylarginine (ADMA) in glomerular capil- lary loss and sclerosis in a rat model of chronic kidney disease (CKD). Life Sci 2009;84:853-6.
  • Kielstein JT, Fliser D. The past, presence and future of ADMA in nephrology. Nephrol Ther 2007; 3: 47-54.
  • Kalita J, Kumar G, Bansal V, Misra UK. Relationship of ho- mocysteine with other risk factors and outcome of isch- emic stroke. Clin Neurol Neurosur 2009;111:364-7.
  • Vrentzos G, Papadakis JA, Malliaraki N, Zacharis EA, Katsogridakis K, Margioris AN. Association of serum total homocysteine with the extent of ischemic heart disease in a Mediterranean cohort. Angiology 2004;55:517-24.
  • Van Guldener C. Why is homocysteine elevated in renal failure and what can be expected from homocysteinelow- ering? Nephrol Dial Transplant 2006;21:1161-6.
  • Rifai N, Ridker PM. Proposed cardiovascular risk assess- ment algorithm using high-sensiıtivity C-reactive protein and lipid screening. Clin Chem 2001;47:28-30.
  • Chen BM, Xia LW, Zhao RQ: Determination of N(G),N(G)- dimethylarginine in human plasma by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1997;692:467–71.
  • Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
  • Eikelboom JW, Lonn E, Genest J, Jr., Hankey G, Yusuf S. Homocysteine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med. 1999;131:363-75.
  • Menon V, Wang X, Greene T, et al. Homocysteine in chron- ic kidney disease: Effect of low protein diet and repletion with B vitamins. Kidney Int 2005;67:1539-46.
  • Sundstrom J, Vasan RS. Homocysteine and heart failure: a review of investigations from the Framingham Heart Study. Clin Chem Lab Med 2005;43:987-92.
  • Refsum H,Helland S, Ueland PM. Radioenzymatic deter- mination of homocysteine in plasma and urine Clin Chem 1985;31:424-8.
  • Anderstam B, Katzarski K, Bergström J (1997) Serum levels of NG,NG-dimethyl-L-arginine, a potential endog- enous nitric oxide inhibitor in dialysis patients. J Am Soc Nephrol 1997;8:1437–42.
  • Oner-Iyidogan Y, Oner P, Kocak H, et al. Dimethylarginines and inflammation markers in patients with chronic kidney disease undergoing dialysis. Clin Exp Med 2009; 9: 235-41.
  • Eiselt J, Rajdl D, Racek J, Siroká R, Trefil L, Opatrná S. Asymmetric dimethylarginine in hemodialysis, hemodi- afiltration, and peritoneal dialysis. Artif Organs 2010;34: 420-5.
  • Kielstein JT, Böger RH, Bode-Böger SM, 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.
  • Zoccali C, Enia G, Tripepi G, Panuccio V, Mallamaci F. Clinical epidemiology of major nontraditional risk fac- tors in peritoneal dialysis patients. Perit Dial Int 2005; 25 Suppl3:84-7.
  • Gutierrez A. Protein catabolism in maintenance haemo- dialysis: the influence of the dialysis membrane. Nephrol Dial Transplant 1996; 11:108–11.
  • Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111:1805-12.
  • Locatelli F, Marcelli D, Conte F, et al. Survival and devel- opment of cardiovascular disease by modality of treat- ment in patients with end-stage renal disease. J Am Soc Nephrol 2001; 12: 2411-7.

Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients

Year 2013, Volume: 10 Issue: 2, 90 - 95, 01.06.2013

Abstract

Kardiyovasküler hastalıklar ve endotelyal disfonksiyon son dönem böbrek yetmezliği hastalarında en önemli ölüm nedenleridir. Periton diyalizi ve hemodiyaliz gibi tedavi yöntemlerinin farklı parametreler üzerine farklı etkileri vardır. Asimetrik dimetilarjinin endojen nitrik oksit sentaz inhibitörüdür ve kronik böbrek yetmezliğinin progresyonunda yeni bir belirteç olduğu gösterilmiştir. Homosistein endotel hasarı, damar düz kas hücre proliferasyonu ve koagülasyon anormallikleri yoluyla trombogenez ve aterogeneze neden olur. Daha önceki çalışmalarda periton diyalizi (PD) ve hemodiyalizin (HD) oksidan ve antioksidan sistemler üzerine etkisiyle ilgili çelişkili bulgular vardır. Bu çalışmada HD, PD ve sağlıklı kişilerde ADMA, homosistein ve CRP düzeylerini belirlemeyi amaçladık. Çalışmaya 44 PD (23E,21K), 26HD (13E,13K) hastası ve 29 (15E,14K) sağlıklı kişi katıldı. ADMA, homosistein, arjinin ve CRP düzeyleri ölçüldü. Son dönem böbrek yetmezliği (SDBY) hastalarının ADMA, homosistein ve CRP düzeyleri sağlıklı kontrol grubuna göre yüksek (p<0.001), arjinin düzeyleri düşük olarak bulundu(p<0.001). HD ve PD gruplarında ADMA, homosistein ve CRP seviyeleri açısından farklılık bulunamadı (sırasıyla p:0.287, p: 0.587, p: 0.835) Bizim sonuçlarımız HD,PD hastalarında sağlıklı kontrole göre ADMA ve homosistein düzeylerinin yüseldiğini gösterdi. Bu bulgular; diyaliz hastalarında endotel disfonksiyonu, inflamasyon ve oksidatif stresin arttığını ve ADMA ve homosistein düzeylerinin diyaliz tedavi yönteminden etkilenmediğini göstermektedir

References

  • United States Renal Data System. VI. Causes of death in ESRD. Am J Kidney Dis 1999;34(2 Suppl 1):87-94.
  • Foly RN, Parfrey PS, Sarnak MJ. Clinical epiıdemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32:112-11ı9.
  • Guebre-Egziabher F, Fougue D Metabolic consequences of inflammation in kidney failure. Nephrologie 2003;24:383–6.
  • Mak RH, Cheung W Adipokines and gut hormones in end- stage renal disease. Perit Dial Int 2007;27(Suppl 2):298–302.
  • Galli F Protein damage and inflammation in uremia and dialysis patients. Nephrol Dial Transplant 2007;22(Suppl 5):20–36.
  • Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C. Oxidative stress in end-stage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant 2003;18:1272–80.
  • Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1994;329:2002–12.
  • Ueda S, Yamagishi S, Matsumoto Y, et al. Involvement of asymmetric dimethylarginine (ADMA) in glomerular capil- lary loss and sclerosis in a rat model of chronic kidney disease (CKD). Life Sci 2009;84:853-6.
  • Kielstein JT, Fliser D. The past, presence and future of ADMA in nephrology. Nephrol Ther 2007; 3: 47-54.
  • Kalita J, Kumar G, Bansal V, Misra UK. Relationship of ho- mocysteine with other risk factors and outcome of isch- emic stroke. Clin Neurol Neurosur 2009;111:364-7.
  • Vrentzos G, Papadakis JA, Malliaraki N, Zacharis EA, Katsogridakis K, Margioris AN. Association of serum total homocysteine with the extent of ischemic heart disease in a Mediterranean cohort. Angiology 2004;55:517-24.
  • Van Guldener C. Why is homocysteine elevated in renal failure and what can be expected from homocysteinelow- ering? Nephrol Dial Transplant 2006;21:1161-6.
  • Rifai N, Ridker PM. Proposed cardiovascular risk assess- ment algorithm using high-sensiıtivity C-reactive protein and lipid screening. Clin Chem 2001;47:28-30.
  • Chen BM, Xia LW, Zhao RQ: Determination of N(G),N(G)- dimethylarginine in human plasma by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1997;692:467–71.
  • Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
  • Eikelboom JW, Lonn E, Genest J, Jr., Hankey G, Yusuf S. Homocysteine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med. 1999;131:363-75.
  • Menon V, Wang X, Greene T, et al. Homocysteine in chron- ic kidney disease: Effect of low protein diet and repletion with B vitamins. Kidney Int 2005;67:1539-46.
  • Sundstrom J, Vasan RS. Homocysteine and heart failure: a review of investigations from the Framingham Heart Study. Clin Chem Lab Med 2005;43:987-92.
  • Refsum H,Helland S, Ueland PM. Radioenzymatic deter- mination of homocysteine in plasma and urine Clin Chem 1985;31:424-8.
  • Anderstam B, Katzarski K, Bergström J (1997) Serum levels of NG,NG-dimethyl-L-arginine, a potential endog- enous nitric oxide inhibitor in dialysis patients. J Am Soc Nephrol 1997;8:1437–42.
  • Oner-Iyidogan Y, Oner P, Kocak H, et al. Dimethylarginines and inflammation markers in patients with chronic kidney disease undergoing dialysis. Clin Exp Med 2009; 9: 235-41.
  • Eiselt J, Rajdl D, Racek J, Siroká R, Trefil L, Opatrná S. Asymmetric dimethylarginine in hemodialysis, hemodi- afiltration, and peritoneal dialysis. Artif Organs 2010;34: 420-5.
  • Kielstein JT, Böger RH, Bode-Böger SM, 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.
  • Zoccali C, Enia G, Tripepi G, Panuccio V, Mallamaci F. Clinical epidemiology of major nontraditional risk fac- tors in peritoneal dialysis patients. Perit Dial Int 2005; 25 Suppl3:84-7.
  • Gutierrez A. Protein catabolism in maintenance haemo- dialysis: the influence of the dialysis membrane. Nephrol Dial Transplant 1996; 11:108–11.
  • Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111:1805-12.
  • Locatelli F, Marcelli D, Conte F, et al. Survival and devel- opment of cardiovascular disease by modality of treat- ment in patients with end-stage renal disease. J Am Soc Nephrol 2001; 12: 2411-7.
There are 27 citations in total.

Details

Primary Language English
Journal Section Original Articles
Authors

Said Sami Erdem This is me

Fatma Hümeyra Yerlikaya This is me

Kültigin Türkmen This is me

Zeki Tonbul This is me

Fatih Mehmet Erdur This is me

Alpaslan Taner This is me

Hümeyra Çiçekler This is me

İdris Mehmetoğlu This is me

Publication Date June 1, 2013
Published in Issue Year 2013 Volume: 10 Issue: 2

Cite

APA Erdem, S. S., Yerlikaya, F. H., Türkmen, K., Tonbul, Z., et al. (2013). Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients. European Journal of General Medicine, 10(2), 90-95.
AMA Erdem SS, Yerlikaya FH, Türkmen K, Tonbul Z, Erdur FM, Taner A, Çiçekler H, Mehmetoğlu İ. Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients. European Journal of General Medicine. June 2013;10(2):90-95.
Chicago Erdem, Said Sami, Fatma Hümeyra Yerlikaya, Kültigin Türkmen, Zeki Tonbul, Fatih Mehmet Erdur, Alpaslan Taner, Hümeyra Çiçekler, and İdris Mehmetoğlu. “Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients”. European Journal of General Medicine 10, no. 2 (June 2013): 90-95.
EndNote Erdem SS, Yerlikaya FH, Türkmen K, Tonbul Z, Erdur FM, Taner A, Çiçekler H, Mehmetoğlu İ (June 1, 2013) Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients. European Journal of General Medicine 10 2 90–95.
IEEE S. S. Erdem, F. H. Yerlikaya, K. Türkmen, Z. Tonbul, F. M. Erdur, A. Taner, H. Çiçekler, and İ. Mehmetoğlu, “Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients”, European Journal of General Medicine, vol. 10, no. 2, pp. 90–95, 2013.
ISNAD Erdem, Said Sami et al. “Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients”. European Journal of General Medicine 10/2 (June 2013), 90-95.
JAMA Erdem SS, Yerlikaya FH, Türkmen K, Tonbul Z, Erdur FM, Taner A, Çiçekler H, Mehmetoğlu İ. Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients. European Journal of General Medicine. 2013;10:90–95.
MLA Erdem, Said Sami et al. “Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients”. European Journal of General Medicine, vol. 10, no. 2, 2013, pp. 90-95.
Vancouver Erdem SS, Yerlikaya FH, Türkmen K, Tonbul Z, Erdur FM, Taner A, Çiçekler H, Mehmetoğlu İ. Asymmetric Dimethylarginine and Homocysteine Levels in Dialysis Patients. European Journal of General Medicine. 2013;10(2):90-5.