Floridi Ardesio, Antolini Francesco, Galli Francesco, Fagugli Riccardo Maria, Floridi Emanuela, Buoncristiani Umberto
Department of Internal Medicine, Section of Applied and Clinical Biochemistry, University of Perugia, Italy.
Nephrol Dial Transplant. 2002 May;17(5):871-8. doi: 10.1093/ndt/17.5.871.
Advanced glycation end-products (AGEs) accumulate in uraemia, regardless of hyperglycaemic conditions, and may contribute to the onset of some long-term complications, such as atherosclerosis, amyloidosis, and neurodegenerative processes. In this study, we compare a daily with a standard 3 times/week dialysis rhythm (DHD and SHD, respectively) in correcting some protein glycation indices in end-stage renal disease (ESRD) patients.
Twenty-one normoglycaemic and 11 diabetic patients on chronic haemodialysis (HD) with low-flux dialysers were studied in a prospective protocol to compare two different dialysis schedules, namely: 4 h, 3 times/week (SHD) and 2 h, 6 times/week (DHD). The patients were studied before and after 6 months of DHD. To further check the effect of DHD on glycation parameters, 4 normoglycaemic HD patients were studied in a third step in which they returned for 3 months to the SHD rhythm. Also, 11 chronic renal failure (CRF) patients not yet on HD and 11 age- and sex-matched healthy controls were studied. A new HPLC method was used to measure the following glycation indexes on plasma: the early product furosine and the advanced products protein-bound and free pentosidine, and two heterogeneous classes of low molecular mass (LMM) AGE peptides.
All the parameters studied showed an accumulation that worsened with the progression of renal failure (controls <CRF <HD). Diabetic patients on SHD showed similar levels of glycation indexes as non-diabetic patients, except for the early product furosine that was notably higher. The shift from SHD to DHD was effective in lowering the concentration of all the glycation parameters measured, both in non-diabetic and diabetic patients. In the total HD population, LMM-AGEs (MM range of approx. 1.5-6.0 kDa) detected at 385 nm emission was lowered by 56% (P<0.001) and LMM-AGEs detected at 440 nm emission and furosine decreased by 23 and 19%, (P< or =0.001 and <0.01, respectively). All these three classes of compounds reached concentrations comparable with those observed in the CRF patients, even if remaining above the control range. The levels of both free and protein-bound pentosidine after DHD decreased by 34% (P<0.001) and 22% (P< or =0.05), respectively. The return for 3 months to SHD in four non-diabetic DHD patients led to a trend toward an increase in all five glycation parameters.
This study demonstrates for the first time that a DHD regimen can effectively lower the mean levels of glycation-related substances observed in SHD. Therefore, DHD can provide a better control of AGE produced in ESRD. This could result in a lower incidence of long-term effects of AGE accumulation in HD.
晚期糖基化终产物（AGEs）在尿毒症中会蓄积，与血糖水平无关，可能会导致一些长期并发症的发生，如动脉粥样硬化、淀粉样变性和神经退行性病变。在本研究中，我们比较每日一次与标准每周3次的透析频率（分别为每日高频透析和标准高频透析）对终末期肾病（ESRD）患者某些蛋白质糖基化指标的改善情况。
采用前瞻性研究方案，对21例血糖正常和11例糖尿病的慢性血液透析（HD）患者（使用低通量透析器）进行研究，比较两种不同的透析方案，即：每周3次，每次4小时（标准高频透析）和每周6次，每次2小时（每日高频透析）。在每日高频透析6个月前后对患者进行研究。为进一步检查每日高频透析对糖基化参数的影响，第三步对4例血糖正常的HD患者进行研究，让他们恢复3个月的标准高频透析频率。此外，还对11例尚未进行HD的慢性肾衰竭（CRF）患者和11例年龄及性别匹配的健康对照者进行了研究。采用一种新的高效液相色谱法测定血浆中的以下糖基化指标：早期产物果糖胺以及晚期产物与蛋白质结合的和游离的戊糖苷，以及两类不同的低分子量（LMM）AGE肽。
所有研究参数均显示随着肾衰竭进展而蓄积加重（对照组＜CRF＜HD）。标准高频透析的糖尿病患者除早期产物果糖胺明显较高外，其糖基化指标水平与非糖尿病患者相似。从标准高频透析转变为每日高频透析可有效降低非糖尿病和糖尿病患者中所有测定的糖基化参数浓度。在所有HD患者中，在385nm发射波长处检测到的LMM - AGEs（分子量范围约为1.5 - 6.0kDa）降低了56%（P＜0.001），在440nm发射波长处检测到的LMM - AGEs和果糖胺分别降低了23%和19%（P分别≤0.001和＜0.01）。这三类化合物的浓度均达到了与CRF患者中观察到的浓度相当的水平，即使仍高于对照范围。每日高频透析后游离和与蛋白质结合的戊糖苷水平分别降低了34%（P＜0.001）和22%（P≤0.05）。4例非糖尿病每日高频透析患者恢复3个月的标准高频透析后，所有五个糖基化参数均有升高趋势。
本研究首次表明，每日高频透析方案可有效降低标准高频透析中观察到的糖基化相关物质的平均水平。因此，每日高频透析可更好地控制ESRD中产生的AGEs。这可能会降低HD中AGEs蓄积的长期影响的发生率。
