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Pyruvate neutralizes peritoneal dialysate cytotoxicity: maintained integrity and proliferation of cultured human
1Division of Nephrology, Hannover Medical School, Germany.
Abstract:
Toxic effects of commercially available peritoneal dialysate (PD) fluid include damage to mesothelial cells (MC), causing a severely disturbed proliferation of cultured MC. We investigated the injury to the cell membrane (by release of lactate dehydrogenase, LDH), the proliferation (by cell counts and by 3H-thymidine incorporation), and optional the cytokine generation (by IL-1 receptor-antagonist production, IL-1 ra) of cultured human MC during the 48 hours after a 30 minute exposure to PD containing either 35 mmol/liter sodium lactate or sodium pyruvate. 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 exposure to the lactate-PD containing 1.36% glucose, LDH activity was increased by more than 30%, proliferation of MC was inhibited by more than 30%, and IL-1 ra production was reduced significantly when compared to pyruvate-PD and the control solution. After preincubation with 3.86% glucose containing PD, all negative effects became even more pronounced in the lactate group whereas the MC maintained their integrity, rate of proliferation and IL-1 ra release after pre-exposure to pyruvate containing PD. These results suggest that the acute toxic effects of commercially available PD on the integrity, proliferation and IL-1 ra production of MC can be avoided by the use of sodium pyruvate instead of sodium lactate.
Insights
Replacing sodium lactate with sodium pyruvate in peritoneal dialysis (PD) fluid significantly reduces toxic effects on mesothelial cells (MC). This switch protects cell membrane integrity, proliferation, and cytokine production, crucial for PD patients.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Peritoneal dialysis (PD) fluid can cause toxic effects on mesothelial cells (MC), impacting cell proliferation and function.
- Understanding these toxic effects is crucial for improving PD fluid formulations and patient outcomes.
Purpose of the Study:
- To investigate the comparative effects of sodium lactate versus sodium pyruvate in PD fluid on human mesothelial cells (MC).
- To assess the impact of PD fluid composition on MC membrane integrity, proliferation, and cytokine production.
Main Methods:
- Cultured human MC were exposed to PD fluids containing either sodium lactate or sodium pyruvate for 30 minutes.
- Assessed cell membrane injury (LDH release), proliferation (cell counts, 3H-thymidine incorporation), and IL-1 receptor antagonist (IL-1 ra) production over 48 hours.
- Tested PD fluids with varying glucose concentrations (1.36% and 3.86%).
Main Results:
- Lactate-containing PD fluid significantly increased LDH activity and inhibited MC proliferation and IL-1 ra production compared to pyruvate-PD and control.
- Higher glucose concentrations (3.86%) exacerbated these negative effects in the lactate group.
- Mesothelial cells maintained integrity, proliferation, and IL-1 ra release when exposed to pyruvate-containing PD fluid, even with higher glucose concentrations.
Conclusions:
- Sodium pyruvate in PD fluid offers a safer alternative to sodium lactate, mitigating acute toxic effects on mesothelial cells.
- Formulation adjustments using pyruvate could improve the biocompatibility of PD fluids.
- This finding has significant implications for optimizing PD therapy and patient care.