Asymmetrical dimethylarginine is associated with renal and cardiovascular outcomes and all-cause mortality in renal transplant recipients

被引:61
作者
Abedini, Sadollah [1 ]
Meinitzer, Andreas [2 ]
Holme, Ingar [3 ,4 ]
Maerz, Winfried [5 ]
Weihrauch, Gisela [6 ]
Fellstrom, Bengt [7 ]
Jardine, Alan [8 ]
Holdaas, Hallvard [9 ]
机构
[1] Toensberg Cty Hosp, Dept Med, Renal Sect, N-3103 Tonsberg, Norway
[2] Clin Inst Med & Chem Lab Diagnost, Graz, Austria
[3] Univ Oslo, Ullevaal Hosp, Dept Prevent Med, N-0407 Oslo, Norway
[4] Univ Oslo, Ullevaal Hosp, Clin Res Ctr, N-0407 Oslo, Norway
[5] Synlab Med Versorgungzentrum Labordiagnost Heidel, Heidelberg, Germany
[6] Med Univ Graz, Clin Inst Med & Chem Lab Diag, Graz, Austria
[7] Univ Hosp, Dept Med Sci, Renal Unit, Uppsala, Sweden
[8] Western Infirm Hosp, Dept Med & Therapeut, Glasgow, Lanark, Scotland
[9] Univ Oslo, Rikshosp, Dept Med, Oslo Univ Hosp, N-0027 Oslo, Norway
关键词
asymmetric dimethylarginine (ADMA); cardiovascular events; death; fluvastatin; renal graft failure; renal transplantation; CHRONIC KIDNEY-DISEASE; NITRIC-OXIDE SYNTHASE; PULSE-WAVE VELOCITY; ARTERIAL STIFFNESS; ENDOTHELIAL DYSFUNCTION; CARDIAC OUTCOMES; RISK-FACTORS; ADMA; INHIBITOR; FLUVASTATIN;
D O I
10.1038/ki.2009.382
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Increased plasma levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and predict the progression to dialysis and death in patients with chronic kidney disease. The effects of these increased ADMA levels in renal transplant recipients, however, are unknown. We used the data from ALERT, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients with stable graft function on enrollment. Patients who were initially randomized to fluvastatin or placebo in the 5- to 6-year trial were offered open-label fluvastatin in a 2-year extension of the original study. After adjustment for baseline values for established factors in this post hoc analysis, ADMA was found to be a significant risk factor for graft failure or doubling of serum creatinine (hazard ratio 2.78), major cardiac events (hazard ratio 2.61), cerebrovascular events (hazard ratio 6.63), and all-cause mortality (hazard ratio 4.87). In this trial extension, the number of end points increased with increasing quartiles of plasma ADMA levels. All end points were significantly increased in the fourth compared to the first quartile. Our study shows that elevated plasma levels of ADMA are associated with increased morbidity, mortality, and the deterioration of graft function in renal transplant recipients. Kidney International (2010) 77, 44-50; doi:10.1038/ki.2009.382; published online 21 October 2009
引用
收藏
页码:44 / 50
页数:7
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