Fragedaki Evangelia, Nebel Michael, Schupp Nicole, Sebekova Katarina, Völkel Wolfgang, Klassen André, Pischetsrieder Monika, Frischmann Matthias, Niwa Toshimitsu, Vienken Jörg, Heidland August, Stopper Helga
Institute of Pharmacology and Toxicology, University of Würzburg, Versbacherstr. 9, D-97080 Würzburg, Germany.
Nephrol Dial Transplant. 2005 Sep;20(9):1936-43. doi: 10.1093/ndt/gfh898. Epub 2005 May 26.
Patients with end-stage renal failure, whether on conservative or haemodialysis therapy, have a high incidence of DNA damage. It is not known if improved control of the uraemic state by daily haemodialysis (DHD) reduces DNA lesions.
DNA damage in peripheral blood lymphocytes (PBLs) was evaluated in a cross-sectional study of 13 patients on DHD (2-3 h, 6 times/week), 12 patients on standard haemodialysis (SHD) therapy (4-5 h, 3 times/week) and 12 healthy age-matched volunteer controls. The biomarker of DNA damage used was micronucleus frequency. The assessed plasma parameters of microinflammation and oxidative stress were C-reactive protein (CRP), interleukin-6 (IL-6), neopterin, advanced oxidation protein products (AOPP), and homocysteine. We also measured plasma concentrations of the circulating advanced glycation end products (AGEs) MGI (methylglyoxal-derived imidazolinone), CML (carboxymethyllysine), imidazolone A (3-deoxyglucosone-derived imidazolinone) and AGE-associated fluorescence.
Compared to SHD, DHD was associated with significantly lower DNA damage, approaching the normal range. Micronuclei (MN) frequency averaged 29.1 MN+/-5.9/1000 binucleated (BN) cells in the SHD group, which is significantly elevated (P<0.01), 14.8 MN+/-4.0/1000 BN cells in the DHD group, and 13.2 MN+/-3.04/1000 BN cells in the controls. CRP and AOPP were in the normal range (and similar between the dialysis groups). In contrast, IL-6 and neopterin were significantly elevated, with lower values associated with DHD as compared with SHD. The increased levels of AGEs tended to be lower in the DHD group, reaching significance for CML and imidazolone A.
Overall, it was found that genomic damage in PBLs is lower in patients on DHD than in those on SHD. Lower plasma concentrations of uraemic toxins, including circulating AGEs, may account for the differences. To confirm these data, prospective clinical trials need to be performed.
终末期肾衰竭患者，无论接受保守治疗还是血液透析治疗，DNA损伤的发生率都很高。目前尚不清楚每日血液透析（DHD）改善尿毒症状态是否能减少DNA损伤。
在一项横断面研究中，对13例接受DHD（2 - 3小时，每周6次）的患者、12例接受标准血液透析（SHD）治疗（4 - 5小时，每周3次）的患者以及12名年龄匹配的健康志愿者进行外周血淋巴细胞（PBL）DNA损伤评估。使用的DNA损伤生物标志物是微核频率。评估的微炎症和氧化应激血浆参数包括C反应蛋白（CRP）、白细胞介素-6（IL - 6）、新蝶呤、晚期氧化蛋白产物（AOPP）和同型半胱氨酸。我们还测量了循环晚期糖基化终产物（AGEs）MGI（甲基乙二醛衍生的咪唑啉酮）、CML（羧甲基赖氨酸）、咪唑啉酮A（3 - 脱氧葡萄糖酮衍生的咪唑啉酮）和AGE相关荧光的血浆浓度。
与SHD相比，DHD与显著更低的DNA损伤相关，接近正常范围。微核（MN）频率在SHD组平均为29.1 MN±5.9/1000双核（BN）细胞，显著升高（P<0.01），在DHD组为14.8 MN±4.0/1000 BN细胞，在对照组为13.2 MN±3.04/1000 BN细胞。CRP和AOPP在正常范围内（透析组之间相似）。相比之下，IL - 6和新蝶呤显著升高，与SHD相比，DHD的值更低。DHD组中AGEs升高水平往往更低，CML和咪唑啉酮A达到显著差异。
总体而言，发现接受DHD的患者外周血淋巴细胞中的基因组损伤低于接受SHD的患者。包括循环AGEs在内的尿毒症毒素血浆浓度较低可能是造成差异的原因。为证实这些数据，需要进行前瞻性临床试验。
