Effects of commercial glucose-based peritoneal dialysates om peripheral blood phagocytes apoptosis

Background:Variable glucose-lactate-based peritoneal dialysates have negati ve effects on peritoneal macrophages and peripheral blood leukocytes, reduc ing the capacity of leukocytes for chemotaxis, bacterial killing. But few r eports exist on cell apoptosis. To investigate the effects of glucose-lacta te-based peritoneal dialysates on cultured phagocytes (monocytes and neutro phils), we focused on studying phagocyte apoptosis after brief exposure to commercial peritoneal dialysates. Methods: Cell apoptosis is measured by flow cytometry (FCM) to detect phosp hatidylserine (PS) exposure on early apoptotic cells using fluorescein-labe led annexin V.To mimic the composition of dialysate in vivo, where the fres hly instilled solution mixes with the residual dialysate from the previous cycle, we performed the experiments using a mixture of fresh and spent dial ysate (9:1). In our transient exposure experiments, monocytes and neutrophi ls were separately incubated in each of the test solutions (1.5% glucose an d 4.25% glucose dialysates) for 10 minutes or 30 minutes and afterward sepa rated and resuspended in RPMI 1640 medium and cultured over the indicated t ime. Results: After exposure to 1.5% glucose dialysates for 10 minutes, monocyte s and neutrophils exhibited normally spontaneous apoptosis. After exposure to 4.25% glucose dialysate, monocytes underwent apoptosis increasingly, 21% +/- 5.0% versus 9.8% +/- 3.6% (p < 0.05) at 24 hours and 47% +/- 6.2% vers us 16% +/- 4.0% (p < 0.01) at 72 hours compared with controls. For neutroph ils, the results were discouraging: hypertonic dialysate not only increased apoptosis [65.36% +/- 2.6% versus 34.17% +/- 8.52% (p < 0.01) at 72 hours] , but also induced cell necrosis. When incubation time was prolonged for 30 minutes, 1.5% dialysate acted like 4.25% dialysate, with the rate of apopt osis increasing rapidly [40% +/- 4.0% versus 16% +/- 4.0% (p < 0.01) at 72 hours for monocytes, and 66.90% +/- 5.6% versus 34.17% +/- 8.52% (p < 0.01) at 72 hours for neutrophils]. Conclusion: Glucose-lactate-based peritoneal dialysates can induce peripher al blood phagocyte apoptosis in vitro, which indicates that glucose plays a n important role in triggering cell apoptosis. Therefore, looking for new, physiologic peritoneal dialysis fluids to replace conventional fluids is re asonable.