Park M S, Kim J K, Holmes C, Weiss M F
Hyonam Kidney Laboratory, Chun Hyang University, Seoul, Korea.
Perit Dial Int. 2000;20 Suppl 5:S33-8.
Advanced glycosylation end-products (AGEs) are associated with diabetic complications and peritoneal damage after long-term peritoneal dialysis (PD) with high glucose dialysis solutions. Glucose degradation products (GDPs) derived during heat sterilization of high glucose dialysis solutions are thought to accelerate AGE formation. A new technique of separating glucose from electrolytes has yielded markedly lower GDP levels and permitted the use of dialysis solutions containing the physiologic buffer bicarbonate. Formation of AGEs in vitro with this new solution is significantly lower compared with formation of AGEs with conventional solutions. The purpose of the present study was to investigate the effect of long-term intraperitoneal use of new, neutral dialysis solution (B/L) containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) on peritoneal AGE accumulation and permeability. Normal male Sprague-Dawley rats were used. Twice daily for 12 weeks, 30 mL of new solution (B/L) or conventional solution [Lac (lactate 40 mmol/L)] was injected into the peritoneal cavity of the test rats. As a control, rats that were not injected were kept for 12 weeks in the same manner as the test rats. After 12 weeks, a 2-hour peritoneal equilibration test (PET) was performed in the test rats. After the PET, the parietal peritoneum and liver were obtained for evaluation of peritoneal morphology and for immunohistochemistry for AGE. Intensity of AGE staining was semi-quantitatively graded from 0 to 3. The omentum was also obtained and immediately frozen for analysis of pentosidine content by high-performance liquid chromatography. Compared with findings in the control group, hematoxylin and eosin staining of the parietal peritoneum and liver samples revealed partial denudation of mesothelial cells in the Lac group; denudation was not remarkable in the B/L group. The B/L solution showed significantly less AGE staining in the peritoneal cavity compared to conventional solution. However, B/L solution failed to lower pentosidine levels. Intraperitoneal volume and the ratio of dialysate glucose at 2 hours to dialysate glucose at instillation (D2/D0 glucose) were significantly lower and the ratio of dialysate urea to plasma urea at 2 hours (D2/P2 urea) was significantly higher in the Lac and B/L groups than in the control group. Intraperitoneal volume was significantly higher in the B/L group than in the Lac group; D2/D glucose and D2P2 urea did not differ between the two groups. In conclusion, peritoneal ultrafiltration decreased after long-term PD. The B/L solution showed a small but statistically significant protective effect against decreasing ultrafiltration as compared with Lac solution. The B/L solution attenuated peritoneal AGE accumulation compared with conventional solution, but did not affect peritoneal pentosidine levels. These findings indicate that biochemical kinetics of various AGE peptides are not unique, but multivalent.
晚期糖基化终末产物（AGEs）与糖尿病并发症以及长期使用高糖透析液进行腹膜透析（PD）后的腹膜损伤有关。高糖透析液热灭菌过程中产生的葡萄糖降解产物（GDPs）被认为会加速AGE的形成。一种将葡萄糖与电解质分离的新技术显著降低了GDP水平，并允许使用含有生理缓冲剂碳酸氢盐的透析液。与传统溶液相比，用这种新溶液在体外形成的AGEs明显更低。本研究的目的是探讨长期腹腔内使用含有碳酸氢盐（25 mmol/L）和乳酸盐（15 mmol/L）的新型中性透析液（B/L）对腹膜AGE蓄积和通透性的影响。使用正常雄性Sprague-Dawley大鼠。试验大鼠每天两次，连续12周，每次向腹腔内注射30 mL新溶液（B/L）或传统溶液[Lac（乳酸盐40 mmol/L）]。作为对照，未注射的大鼠以与试验大鼠相同的方式饲养12周。12周后，对试验大鼠进行2小时的腹膜平衡试验（PET）。PET后，获取壁层腹膜和肝脏，用于评估腹膜形态和进行AGE的免疫组织化学检测。AGE染色强度从0到3进行半定量分级。还获取大网膜并立即冷冻，通过高效液相色谱分析戊糖苷含量。与对照组结果相比，壁层腹膜和肝脏样本的苏木精-伊红染色显示，Lac组间皮细胞有部分剥脱；B/L组剥脱不明显。与传统溶液相比，B/L溶液在腹膜腔中的AGE染色明显减少。然而，B/L溶液未能降低戊糖苷水平。Lac组和B/L组的腹腔内液体量以及2小时透析液葡萄糖与注入时透析液葡萄糖的比值（D2/D0葡萄糖）显著低于对照组，2小时透析液尿素与血浆尿素的比值（D2/P2尿素）显著高于对照组。B/L组的腹腔内液体量显著高于Lac组；两组间D2/D葡萄糖和D2P2尿素无差异。总之，长期腹膜透析后腹膜超滤减少。与Lac溶液相比，B/L溶液对超滤减少显示出小但具有统计学意义的保护作用。与传统溶液相比，B/L溶液减轻了腹膜AGE蓄积，但不影响腹膜戊糖苷水平。这些发现表明，各种AGE肽的生化动力学并非单一的，而是多价的。
