Jörres A, Gahl G M, Frei U
Abteilung für Innere Medizin mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Virchow-Klinikum, Berlin, Germany.
Perit Dial Int. 1995;15(7 Suppl):S41-5; discussion S45-6.
Within the limitations of the various experimental protocols there appears to be agreement in the literature that unused dialysis fluids, at least when studied in vitro, adversely affect multiple leukocyte functions. The effects of dialysis fluids on leukocytes that have been reported to date include: 1. Decreased cell viability of PMNs, PM phis, PBMCs, and lymphocytes; 2. Inhibited phagocytosis and bacterial killing of various microorganisms by PM phis, PMNs, and peripheral blood leukocytes; 3. Reduced secretion of leukotrienes (LTB4, LTC4) from peritoneal and peripheral blood PMNs and PBMCs; 4. Reduced secretion of prostaglandins (PGE2, TXB2 and 6-keto-PGF1 alpha) from PM phi; 5. Decreased production of many cytokines including TNF alpha, IL-8, and IL-6 in PM phis and PBMCs. In addition, several studies targeting the potential mechanisms by which dialysis solutions inhibit leukocyte function identified the initial low pH of the fluids in combination with their lactate content as being of primary relevance, since they may lead to a rapid intracellular acidification of leukocytes. Moreover, some studies indicated the importance of fluid hyperosmolarity and excessive glucose concentrations. These results are indirectly supported by recent in vitro investigations of alternative fluids, which showed improved leukocyte function following exposure to solutions with neutral pH, bicarbonate buffer instead of lactate, or normal osmolarity due to use of an alternative osmotic agent (e.g., glucose polymer). In conclusion, the evidence obtained during in vitro experimentation suggests that current dialysis fluids are, indeed, not biocompatible. However, whether this also bears physiological relevance in vivo remains to be established in controlled clinical trials comparing conventional fluids to alternative solutions with improved biocompatibility. With regard to the future development of in vitro models for biocompatibility assessment, the following guidelines are suggested: 1. Cell functional parameters should be studied in more than one cell population; 2. Depending on which fluid aspect is under investigation, short or even very short exposure times should be used (e.g., < 30 min for pH/buffer studies; < 4 hours for osmolality/osmotic agent studies); 3. In case the parameter/readout of interest requires longer study periods than indicated above (e.g., studies of cytokine induction or surface receptor expression), preincubation/recovery models should be preferred over coincubation experiments.
在各种实验方案的局限性范围内，文献中似乎存在共识，即未使用的透析液，至少在体外研究时，会对多种白细胞功能产生不利影响。迄今为止报道的透析液对白细胞的影响包括：1. 中性粒细胞、多形核白细胞、外周血单核细胞和淋巴细胞的细胞活力降低；2. 多形核白细胞、中性粒细胞和外周血白细胞对各种微生物的吞噬作用和细菌杀伤能力受到抑制；3. 腹膜和外周血中性粒细胞及外周血单核细胞中白三烯（LTB4、LTC4）的分泌减少；4. 多形核白细胞中前列腺素（PGE2、TXB2和6-酮-PGF1α）的分泌减少；5. 多形核白细胞和外周血单核细胞中包括肿瘤坏死因子α、白细胞介素-8和白细胞介素-6在内的多种细胞因子的产生减少。此外，一些针对透析液抑制白细胞功能潜在机制的研究确定，透析液最初的低pH值及其乳酸含量具有主要相关性，因为它们可能导致白细胞细胞内迅速酸化。此外，一些研究表明了液体高渗和葡萄糖浓度过高的重要性。最近对替代液的体外研究间接支持了这些结果，这些研究表明，暴露于中性pH、用碳酸氢盐缓冲液替代乳酸盐或由于使用替代渗透剂（如葡萄糖聚合物）而具有正常渗透压的溶液后，白细胞功能得到改善。总之，体外实验获得的证据表明，目前的透析液确实不具有生物相容性。然而，这在体内是否也具有生理相关性，仍有待在将传统透析液与具有改善生物相容性的替代溶液进行比较的对照临床试验中确定。关于生物相容性评估体外模型的未来发展，建议遵循以下指导原则：1. 应在多个细胞群体中研究细胞功能参数；2. 根据所研究的透析液方面，应使用短时间甚至非常短的暴露时间（例如，pH/缓冲液研究<30分钟；渗透压/渗透剂研究<4小时）；3. 如果感兴趣的参数/读数需要比上述更长的研究时间（例如，细胞因子诱导或表面受体表达的研究），预孵育/恢复模型应优先于共孵育实验。
