血液透析对ADMA的清除作用及与NO生成的相关性研究

Clinical trail on asymmetric dimethylarginine clearance by hemodialysis and its correlation with nitric oxide production

目的观察血液透析对尿毒症患者体内非对称性二甲基精氨酸(asymmetic dimethyl arginine,ADMA)的清除作用及与一氧化氮(nitricoxide,NO)生成的相关关系。方法选择单中心维持性血液透析(maintenance hemodialysis,MHD)患者159例,检测透析前、后血清ADMA和一氧化氮代谢产物(nitricoxide productions,NOx)的浓度,测算单次透析清除ADMA和NOx的总量,对比MHD患者透析前后、MHD患者与健康对照、MHD患者不同年龄组、糖尿病与非糖尿病组、高血压、低血压与血压稳定组之间透析前血清ADMA及NOx的浓度,对透析前和透析后血清ADMA与NOx浓度分别进行相关性分析。结果MHD患者透析后血清ADMA水平明显降低[(1.05±0.67)μmol/L比(0.83±0.53)μmol/L,P<0.001],NOx水平明显升高[(61.1±38.5)μmol/L比(96.1±58.1)μmol/L,P<0.001];4h血液透析对ADMA和NOx的总清除量为[(9.15±4.70)μmol和(448.62±58.59)μmol];与健康人相比,MHD患者透析前后ADMA水平都高[(1.05±0.67)μmol/L、(0.83±0.53)μmol/L比(0.35±0.06)μmol/L,P值分别为0.002和0.004],NOx水平则相当[(61.1±38.5)μmol/L、(96.1±58.1)μmol/L比(68.1±13.6)μmol/L,P值分别为0.596和0.166];MHD患者各组之间透析前血清ADMA与NOx水平差异均无统计学意义;透析前、后ADMA与NOx水平均呈明显负相关关系(r分别为-0.344和-0.612,P值分别为0.047和0.001)。结论MHD患者透析前血清ADMA水平高于健康人,NOx水平与健康人相当;血液透析可以清除ADMA和NOx,对ADMA的清除作用相对要小;透析后血清NOx水平升高可能与透析清除ADMA等抑制NO生成的物质有关。

Objective To study the correlation between clearance of asymmetric dimethylarginine （ADMA） by hemodialysis and nitric oxide （NO） production in maintenance hemodialysis patients （MHD）. Methods Serum ADMA and NO productions （NOx） were measured in 159 MHD patients before and after the dialysis, from which the clearance of ADMA and NOx after the 4-hour dialysis treatment can be calculated. Samples from 20 healthy individuals were used as the controls. Serum ADMA and NOx before and after dialysis were compared. The comparison was also made in MHD patients and normal controls, MHD patients older than 65 years and those less than 65 years, MHD patients with diabetes and those without diabetes, and MHD patients with hypertension, hypotension, and stable blood pressure. Correlation analysis was performed to serum ADMA and NOx before and after the dialysis. Results In MHD patients after the dialysis, serum ADMA decreased[（1.05±0.67）μmol/L vs （0.83±0.53）μmol/ L, P〈0.001], and serum NOx increased [（61.1±38.5）μmol/L vs （96.1±58.1）μmol/L, P〈0.001]. The clearance of ADMA and NOx after 4-hour dialysis ranged （9.15 ±4.70）μmol and （448.62±58.59）μmol, respectively. MHD patients had higher serum ADMA before dialysis [（1.05±0.67）μmol/L, P =0.002] and after dialysis [（0.83±0.53μmol/L, P = 0.004], as compared with serum ADMA of normal controls （0.35±0.06μmol/L）. However, MHD patients had relatively unchanged serum NOx before dialysis [（61.1±38.5）μmol/L, P = 0.596] and after dialysis [（96.1±58.1）μmol/L, P = 0.166], as compared with that of the normal controls [（68.1±13.6）μmol/L]. Among the subgroups of HMD patients, no significant differences in serum ADMA and NOx were detected before dialysis, but negative correlation was found between serum ADMA and NOx before the dialysis （r = -0.344, P = 0.047） and after dialysis （r = -0.612, P = 0.001）. Conclusion In HMD patients before dialysis, serum ADMA increased, and serum NOx was similar to the value of normal controls. Hemodialyis is capable to remove ADMA and NOx, although the clearance of ADMA is insufficient. The increase of serum NOx after dialysis may result from the removal of ADMA.