Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in renal failure patients

Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in renal failure patients
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DOI:
10.1046/j.1523-1755.2001.59780014.x
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发表时间:
2001-02-01
影响因子:
19.6
通讯作者:
Stein, G
Stein, G
中科院分区:
医学1区
文献类型:
--
作者:
Fleck, C;Janz, A;Stein, G

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背景肾功能衰竭患者血浆中积累的ADMA可抑制一氧化氮(NO)的合成,但SDMA的浓度也会升高。因此,有人假设ADMA和SDMA可能导致这些患者的高血压。采用高效液相色谱法测定了257例正常人血清中ADMA、SDMA及21种内源性氨基酸的含量。慢性肾功能衰竭(CRF)患者血浆ADMA和SDMA浓度均显著升高。SDMA的增加更为明显(2.05 +/- 0.1 μ mol/L vs. 0.5 +/- 0.03 μ mol/L),而ADMA的增加仅为中度(0.85 +/- 0.03 μ mol/L vs. 0.73 +/- 0.06 μ mol/L)。在透析患者中,浓度进一步升高(ADMA,1.05 +/- 0.04 μ mol/L; SDMA,2.68 +/- 0.13 μ mol/L)。肾移植后SDMA浓度恢复至基线值(1.15 ± 0.11 μ mol/L),而ADMA浓度仍升高(0.99 ± 0.06 μ mol/L)。在CRF中,特别是SDMA浓度显著升高。不仅ADMA,而且SDMA也可能是高血压的原因。在解释肾衰竭时二甲基精氨酸和精氨酸之间的比例变化时,必须考虑SDMA和精氨酸在肾脏内的重吸收竞争。血液透析不适合长期清除甲基精氨酸。精氨酸的应用是否对高血压和CRF并发症有良好的疗效,还需要进行前瞻性研究。
Background. Nitric oxide (NO) synthesis is inhibited by the ADMA that accumulates in the plasma of patients with renal failure, however, the concentration of SDMA also is enhanced. Therefore, it has been hypothesized that ADMA and SDMA may contribute to hypertension in these patients.Methods. We measured the concentrations of ADMA, SDMA and 21 endogenous amino acids in 257 persons by high pressure liquid chromatography (HPLC).Results. The plasma concentrations of both ADMA and SDMA were significantly elevated in patients with chronic renal failure (CRF). The increase was more pronounced for SDMA (2.05 +/- 0.1 mu mol/L vs. 0.5 +/- 0.03 mu mol/L), whereas it was only moderate for ADMA (0.85 +/- 0.03 mu mol/L vs. 0.73 +/- 0.06 mu mol/L). In dialysis patients, the concentrations were further increased (ADMA, 1.05 +/- 0.04 mu mol/L; SDMA, 2.68 +/- 0.13 mu mol/L). After kidney transplantation, the concentration of SDMA returned to the baseline value (1.15 +/- 0.11 mu mol/L), but that of ADMA remained enhanced (0.99 +/- 0.06 mu mol/L).Conclusions. In CRF, especially the concentration of SDMA is significantly increased. Not only ADMA, but also SDMA are likely to be responsible for hypertension. Competition for reabsorption between SDMA and arginine within the kidney has to be considered fur the interpretation of changes in the ratio between dimethylarginines and arginine in renal failure. Hemodialysis is not suitable for a long-lasting removal of methylarginines. Whether the administration of arginine could have promising effects on hypertension and complications of CRF needs to be studied in prospective trials.