Miyata T, Ueda Y, Yoshida A, Sugiyama S, Iida Y, Jadoul M, Maeda K, Kurokawa K, van Ypersele de Strihou C
Department of Internal Medicine, Branch Hospital, Nagoya University School of Medicine, Japan.
Kidney Int. 1997 Mar;51(3):880-7. doi: 10.1038/ki.1997.124.
We recently demonstrated that pentosidine, an advanced glycation end product, accumulates markedly as albumin-linked form (Palb) and in free-form (Pfree) in the plasma of patients with end-stage renal failure. The present study was undertaken to examine the clearance of Palb and Pfree by different modalities of renal replacement therapy, that is, hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), and renal transplantation. HD cleared Pfree (9.4 +/- 4.3 nmol/kg/HD) but not Palb, by diffusion but not by membrane adsorption, whereas CAPD cleared both Palb (4.03 +/- 2.01 nmol/kg/day) and Pfree (2.43 +/- 1.24 nmol/kg/day). Plasma total pentosidine levels were significantly (P < 0.05) lower in CAPD (0.97 +/- 0.41 nmol/ml) than in HD (1.19 +/- 0.41 nmol/ml), as the result of a lower serum albumin level in the former patients. Indeed, Palb expressed per mg albumin was virtually identical in HD and CAPD. By contrast, Pfree was significantly lower in CAPD than in HD. Palb levels were significantly correlated with plasma Pfree levels in both HD and CAPD patients, but not in the CAPD dialysate. Pentosidine transport across the peritoneum occurs mainly by diffusion, both as Palb and Pfree. Interestingly, peritoneal Palb clearance (0.17 +/- 0.07 ml/min) significantly (P < 0.00001) exceeded albumin clearance (0.11 +/- 0.05 ml/min). Palb levels being significantly higher (P < 0.0005) in the peritoneal fluid (36.28 +/- 18.55 pmol/mg) than in the serum (27.12 +/- 11.71 pmol/mg), thus raises the possibility of a facilitated diffusion of Palb or an active transport mechanism for protein-linked pentosidine into the peritoneal cavity. After renal transplantation, plasma Pfree fell rapidly, remained barely detectable after one month, and returned to normal at six months. By contrast, Palb fell more slowly and remained significantly above normal at six months, but returned eventually to normal levels. These findings demonstrate that: (1) both HD and CAPD remove Pfree; (2) the peritoneal clearance of Palb, might contribute to the lower level of plasma pentosidine in CAPD than in HD patients; and (3) renal transplantation is the best therapeutic modality to normalize both Palb and Pfree levels.
我们最近证明，晚期糖基化终产物戊糖苷在终末期肾衰竭患者血浆中以与白蛋白结合的形式（Palb）和游离形式（Pfree）显著蓄积。本研究旨在探讨不同肾脏替代治疗方式，即血液透析（HD）、持续性非卧床腹膜透析（CAPD）和肾移植对Palb和Pfree的清除情况。HD通过扩散而非膜吸附清除Pfree（9.4±4.3 nmol/kg/HD），但不能清除Palb，而CAPD可清除Palb（4.03±2.01 nmol/kg/天）和Pfree（2.43±1.24 nmol/kg/天）。由于CAPD患者血清白蛋白水平较低，其血浆总戊糖苷水平（0.97±0.41 nmol/ml）显著低于HD患者（1.19±0.41 nmol/ml）（P<0.05）。实际上，HD和CAPD中每毫克白蛋白所含Palb几乎相同。相比之下，CAPD中的Pfree显著低于HD。HD和CAPD患者的Palb水平均与血浆Pfree水平显著相关，但在CAPD透析液中则不然。戊糖苷以Palb和Pfree形式通过腹膜的转运主要通过扩散进行。有趣的是，腹膜Palb清除率（0.17±0.07 ml/min）显著高于白蛋白清除率（0.11±0.05 ml/min）（P<0.00001）。腹膜液中Palb水平（36.28±18.55 pmol/mg）显著高于血清（27.12±11.71 pmol/mg）（P<0.0005），这提示Palb可能存在易化扩散或蛋白结合型戊糖苷存在主动转运机制进入腹膜腔。肾移植后，血浆Pfree迅速下降，1个月后几乎检测不到，6个月时恢复正常。相比之下，Palb下降较慢，6个月时仍显著高于正常水平，但最终恢复至正常水平。这些结果表明：（1）HD和CAPD均可清除Pfree；（2）Palb的腹膜清除可能是CAPD患者血浆戊糖苷水平低于HD患者的原因之一；（3）肾移植是使Palb和Pfree水平均恢复正常的最佳治疗方式。
