PYRUVATE NEUTRALIZES PERITONEAL DIALYSATE CYTOTOXICITY - MAINTAINED INTEGRITY AND PROLIFERATION OF CULTURED HUMAN MESOTHELIAL CELLS

Toxic effects of commercially available peritoneal dialysate (PD) flui d include damage to mesothelial cells (MC), causing a severely disturb ed proliferation of cultured MC. We investigated the injury to the cel l membrane (by release of lactate dehydrogenase, LDH), the proliferati on (by cell counts and by H-3-thymidine incorporation), and optional t he cytokine generation (by IL-1 receptor-antagonist production, IL-1 r a) of cultured human MC during the 48 hours after a 30 minute exposure to PD containing either 35 mmol/liter sodium lactate or sodium pyruva te. All solutions had a pH of 5.2 to 5.6 and were composed as standard PD. Glucose contents of 1.36 and 3.86 mmol/liter were tested. After e xposure to the lactate-PD containing 1.36% glucose, LDH activity was i ncreased by more than 30%, proliferation of MC was inhibited by more t han 30%, and IL-1 ra production was reduced significantly when compare d to pyruvate-PD and the control solution. After preincubation with 3. 86% glucose containing PD, all negative effects became even more prono unced in the lactate group whereas the MC maintained their integrity, rate of proliferation and IL-1 ra release after pre-exposure to pyruva te containing PD. These results suggest that the acute toxic effects o f commercially available PD on the integrity, proliferation and IL-1 r a production of MC can be avoided by the use of sodium pyruvate instea d of sodium lactate.