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2013 | 8 | 3 | 346-353
Tytuł artykułu

ADMA and C-reactive protein as mortality predictors in dialysis patients

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There is a higher mortality between patients with end-stage renal disease than patients in the general population. These circumstances have led to a search for risk factors as predictors of mortality in dialysis patients. Amongst those, inhibitors of the nitric-oxide (NO) synthesis deserve special attention, since patients with end-stage renal disease are also characterized by accelerated atherosclerosis. Asymmetric-dimethylarginine (ADMA) and symmetric-dimethylarginine (SDMA), as well as C-reactive protein (CRP), have also been recognized as predictors of mortality in patients on dialysis. The aim of our study was to compare the prediction power of ADMA, SDMA and CRP for all-cause mortality in patients with end stage renal disease during the fourteen month follow-up. In total 162 patients on hemodialysis were included. ADMA and SDMA were measured by the high-performance liquid chromatography (HPLC); CRP was measured using immunonephelometric assays. During the 14-month period 28 patients (34.1%) died from all-cause mortality. Using univariate analysis, hazard ratios (HR) of the potential independent predictors of mortality in hemodialysis patients were ADMA (HR 1.39 (1.01–1.91) p=0.043) and CRP (HR 1.024 (1.009–1.1.040) p=0.001). Further, multivariate analysis (MVA), however, showed that ADMA is the only predictor of all-cause mortality (HR 1.76 (1.002–3.11) P=0.049), while SDMA failed to predict death in this population. Therefore, our data shows that ADMA is an independent and better marker of all-cause mortality compared with CRP.

Opis fizyczny
  • Faculty of Medicine Niš, Research Centre for Biomedicine, University of Niš, Bulvd. Zorana Djindjica 81, 18000, Nis, Serbia
  • Clinical Centre Niš, Clinic of nephrology, Bulvd. Zorana Djindjica 48, 18000, Nis, Serbia
  • Faculty of Medicine Niš, Department of Medical Statistics, University of Niš, Bulvd. Zorana Djindjica 81, 18000, Nis, Serbia
  • Faculty of Medicine Niš, Institute of Biochemistry, University of Niš, Bulvd. Zorana Djindjica 81, 18000, Nis, Serbia
  • Faculty of Medicine Niš, Institute of Biochemistry, University of Niš, Bulvd. Zorana Djindjica 81, 18000, Nis, Serbia
  • Faculty of Medicine Niš, Institute of Biochemistry, University of Niš, Bulvd. Zorana Djindjica 81, 18000, Nis, Serbia
  • Faculty of Medicine Niš, Research Centre for Biomedicine, University of Niš, Bulvd. Zorana Djindjica 81, 18000, Nis, Serbia
  • [1] Foley RN, Parfrey PS Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol. 1998,9(12 Suppl),S16–23
  • [2] Vanholder R, Massy Z, Argiles A, Spasovski G, Verbeke F Lameire N. Chronic kidney disease as cause of cardiovascular morbidity and mortality. Nephrol Dial Transplant. 2005,20(6),1048–1056[Crossref]
  • [3] Lindner A, Charra B, Sherrard DJ Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med. 1974,290(13),697–701[Crossref]
  • [4] Cighetti G, Fermo I, Aman CS, Ferraroni M, Secchi A, Fiorina P, et al. Dimethylarginines in complicated type 1 diabetes: roles of insulin, glucose, and oxidative stress. Free Radic Biol Med. 2009,47(3),307–311[WoS]
  • [5] Vallance P, Leone A, Calver A, Collier J Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet. 1992,339(8793),572–575[Crossref]
  • [6] Oner-Iyidogan Y, Oner P, Kocak H, Gurdol F, Bekpinar S, Unlucerci Y, et al. Dimethylarginines and inflammation markers in patients with chronic kidney disease undergoing dialysis. Clin Exp Med. 2009,9(3),235–241[Crossref]
  • [7] Zoccali C Kielstein JT. Asymmetric dimethylarginine: a new player in the pathogenesis of renal disease? Curr Opin Nephrol Hypertens. 2006,15(3),314–320[Crossref]
  • [8] Zoccali C, Benedetto FA, Maas R, Mallamaci F, Tripepi G, Malatino LS, et al. Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease. J Am Soc Nephrol. 2002,13(2),490–496
  • [9] Furuki K, Adachi H, Matsuoka H, Enomoto M, Satoh A, Hino A, et al. Plasma levels of asymmetric dimethylarginine (ADMA) are related to intima-media thickness of the carotid artery: an epidemiological study. Atherosclerosis. 2007,191(1),206–210[Crossref][WoS]
  • [10] Zeller M, Korandji C, Guilland JC, Sicard P, Vergely C, Lorgis L, et al. Impact of asymmetric dimethylarginine on mortality after acute myocardial infarction. Arterioscler Thromb Vasc Biol. 2008,28(5),954–960[Crossref]
  • [11] Aucella F, Maas R, Vigilante M, Tripepi G, Schwedhelm E, Margaglione M, et al. Methylarginines and mortality in patients with end stage renal disease: a prospective cohort study. Atherosclerosis. 2009,207(2),541–545[Crossref]
  • [12] Boger RH, Endres HG, Schwedhelm E, Darius H, Atzler D, Luneburg N, et al. Asymmetric dimethylarginine as an independent risk marker for mortality in ambulatory patients with peripheral arterial disease. J Intern Med. 2011,269(3),349–361[WoS][Crossref]
  • [13] Wilson AM, Shin DS, Weatherby C, Harada RK, Ng MK, Nair N, et al. Asymmetric dimethylarginine correlates with measures of disease severity, major adverse cardiovascular events and all-cause mortality in patients with peripheral arterial disease. Vasc Med. 2010,15(4),267–274[WoS][Crossref]
  • [14] Iapichino G, Albicini M, Umbrello M, Sacconi F, Fermo I, Pavlovich R, et al. Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients. Intensive Care Med. 2008, 34(10),1843–50[Crossref]
  • [15] Fliser D, Kronenberg F, Kielstein JT, Morath C, Bode-Boger SM, Haller H, et al. Asymmetric dimethylarginine and progression of chronic kidney disease: the mild to moderate kidney disease study. J Am Soc Nephrol. 2005,16(8),2456–2461[Crossref]
  • [16] Bode-Boger SM, Scalera F, Kielstein JT, Martens-Lobenhoffer J, Breithardt G, Fobker M, et al. Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary artery disease. J Am Soc Nephrol. 2006,17(4), 1128–1134[Crossref]
  • [17] Schindler R, Boenisch O, Fischer C, Frei U. Effect of the hemodialysis membrane on the inflammatory reaction in vivo. Clin Nephrol. 2000,53(6),452–459
  • [18] Zoccali C, Mallamaci F Tripepi G. Inflammation and atherosclerosis in end-stage renal disease. Blood Purif. 2003,21(1),29–36[Crossref]
  • [19] Wanner C, Zimmermann J, Schwedler S, Metzger T. Inflammation and cardiovascular risk in dialysis patients. Kidney Int Suppl. 2002, (80), 99–102 [Crossref]
  • [20] Pecoits-Filho R, Barany P, Lindholm B, Heimburger O Stenvinkel P. Interleukin-6 is an independent predictor of mortality in patients starting dialysis treatment. Nephrol Dial Transplant. 2002,17(9),1684–1648[Crossref]
  • [21] Panichi V, Maggiore U, Taccola D, Migliori M, Rizza GM, Consani C, et al. Interleukin-6 is a stronger predictor of total and cardiovascular mortality than C-reactive protein in haemodialysis patients. Nephrol Dial Transplant. 2004,19(5),1154–1160[Crossref]
  • [22] Paroni R, Fermo I, Fiorina P Cighetti G. Determination of asymmetric and symmetric dimethylarginines in plasma of hyperhomocysteinemic subjects. Amino Acids. 2005,28(4),389–394[Crossref]
  • [23] Teerlink T, Nijveldt RJ, de Jong S van Leeuwen PA. Determination of arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma and other biological samples by high-performance liquid chromatography. Anal Biochem. 2002,303(2),131–137[Crossref]
  • [24] Zoccali C, Bode-Boger S, Mallamaci F, Benedetto F, Tripepi G, Malatino L, et al. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet. 2001,358(9299),2113–2117[Crossref]
  • [25] 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),2449–2455[Crossref]
  • [26] Kumagai H, Sakurai M, Takita T, Maruyama Y, Uno S, Ikegaya N, et al. Association of homocysteine and asymmetric dimethylarginine with atherosclerosis and cardiovascular events in maintenance hemodialysis patients. Am J Kidney Dis. 2006,48(5),797–805[Crossref]
  • [27] Busch M, Fleck C, Wolf G Stein G. Asymmetrical (ADMA) and symmetrical dimethylarginine (SDMA) as potential risk factors for cardiovascular and renal outcome in chronic kidney disease - possible candidates for paradoxical epidemiology? Amino Acids. 2006,30(3),225–232[Crossref]
  • [28] Lee JH, Cook JR, Yang ZH, Mirochnitchenko O, Gunderson SI, Felix AM, et al. PRMT7, a new protein arginine methyltransferase that synthesizes symmetric dimethylarginine. J Biol Chem. 2005, 280(5),3656–3664[Crossref]
  • [29] Richard S, Morel M Cleroux P. Arginine methylation regulates IL-2 gene expression: a role for protein arginine methyltransferase 5 (PRMT5). Biochem J. 2005,388(Pt 1),379–386
  • [30] Boger RH, Sydow K, Borlak J, Thum T, Lenzen H, Schubert B, et al. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res. 2000, 87(2),99–105[Crossref]
  • [31] Tran CT, Leipe JM Vallance P. The DDAH/ADMA/NOS pathway. Atheroscler Suppl. 2003,4(4),33–40[Crossref]
  • [32] 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), 3092–3095[Crossref]
  • [33] Stuhlinger MC, Tsao PS, Her JH, Kimoto M, Balint RF, Cooke JP. Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine. Circulation 2001,104(21), 2569–2575[Crossref]
  • [34] Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 2002,106(8), 987–992[Crossref]
  • [35] Weis M, Kledal TN, Lin KY, Panchal SN, Gao SZ, Valantine HA, et al. Cytomegalovirus infection impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine in transplant arteriosclerosis. Circulation. 2004,109(4),500–505[Crossref]
  • [36] Tripepi G, Mallamaci F, Zoccali C. Inflammation markers, adhesion molecules, and all-cause and cardiovascular mortality in patients with ESRD: searching for the best risk marker by multivariate modeling. J Am Soc Nephrol. 2005,16 Suppl 1,S83–88[Crossref]
  • [37] Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int. 1999,55(2),648–658[Crossref]
  • [38] Kato A, Takita T, Furuhashi M, Maruyama Y, Hishida A. Comparison of serum albumin, C-reactive protein and carotid atherosclerosis as predictors of 10-year mortality in hemodialysis patients. Hemodial Int. 2010,14(2),226–232[Crossref][WoS]
  • [39] 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(6),2330–2337[Crossref]
  • [40] Tripepi G, Mattace Raso F, Sijbrands E, Seck MS, Maas R, Boger R, et al. Inflammation and asymmetric dimethylarginine for predicting death and cardiovascular events in ESRD patients. Clin J Am Soc Nephrol. 2011,6(7),1714–1721[WoS][Crossref]
  • [41] Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004,350(14),1387–1397[Crossref]
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