James B. Moberly

Apolipoprotein C-III, Hypertriglyceridemia and Triglyceride-Rich Lipoproteins in Uremia

Apolipoprotein C-III (ApoC-III) plays an important role in the metabolism of triglyceride-rich lipoproteins and is known to be elevated in patients with uremia. To investigate the role of apoC-III in uremic dyslipidemia, we examined apoC-III, triglyceride levels and lipoprotein particles containing both apoB and apoC-III (LP-Bc) in 27 uremic patients prior to dialysis (predialysis), 30 patients on hemodialysis (HD) and 31 patients on peritoneal dialysis (PD). All three groups of patients had elevated levels of plasma apoC-III (20±7 mg/dl for predialysis, 18±5 for HD and 22±8 for PD, compared to 11±3 mg/dl for control subjects [p<0/01 for all comparisons]). ApoC-III was positively correlated with plasma triglycerides in PD patients (r = 0.86, p<0.0001), HD patients (r = 0.67, p<0.0001) and predialysis patients (r = 0.60, p<0.001) as well as in all patients combined (r = 0.75, p<0.0001). ApoC-III was also positively correlated with levels of LP-Bc in all three groups of patients, although this correlation was less strong (r = 0.46, p<0.0001 for all patients combined). In predialysis and PD patients, the majority of apoC-III was found in heparin precipitable lipoproteins, whereas the majority of apoC-III in HD patients was found in HDL, indicating less efficient lipolysis in predialysis and PD patients in comparison with HD. These data support the hypothesis that the elevation of apoC-III in uremia can alter the metabolism of triglyceride-rich lipoproteins, leading to an elevation in triglycerides and LP-Bc. Understanding the mechanism(s) of elevated apoC-III in uremia may help to clarify the causes of uremic dyslipidemia.

Effect of Haluronan-Supplemented Dialysate on in vitro Function of Human Peritoneal Mesothelial Cells

Background: Addition of hyaluronan (HA) to the dialysis solution has been suggested as a means to protect the peritoneum from injury during peritoneal dialysis (PD). Methods: Concentrations of inflammatory mediators were determined in dialysate samples obtained from PD patients after 6-hour dwells with glucose-based (13.6 g/l) solution containing 0.1 and 0.5 g/l of exogenous high-molecular-weight HA. We additionally evaluated the effect of HA-supplemented dialysate, drained after dwell in PD patients, on function of human peritoneal mesothelial cells (MC) in in vitro culture. Results: Concentration of nitrites was significantly higher in HA 0.5 g/l supplemented dialysate (+43%, p < 0.05) as compared to control. Levels of monocyte chemoattractant protein (MCP-1), soluble intercellular adhesive molecule (s-ICAM), vascular endothelial growth factor (VEGF) and fibronectin were comparable in all the studied groups. However, when MC were exposed in in vitro conditions for 24 h to the studied dialysates, we observed that HA containing fluids inhibited the synthesis of MCP-1, s-ICAM, VEGF and fibronectin in these cells. HA-supplemented dialysate accelerated growth rate of in vitro proliferating MC. Conclusion: High-molecular-weight HA added to the dialysis fluid exerts anti-inflammatory and antifibrotic actions on the in vitro cultured MC and accelerates their growth rate what may be important for peritoneal healing during PD.