Impact of a low-glucose peritoneal dialysis regimen on fibrosis and inflammation biomarkers

Abstract

Background: The impact of a low-glucose peritoneal dialysis (PD) regimen on biomarkers of peritoneal inflammation, fibrosis and membrane integrity remains to be investigated.

Methods: In a randomized, prospective study, 80 incident PD patients received either a low-glucose regimen comprising Physioneal (P), Extraneal (E) and Nutrineal (N) (Baxter Healthcare Corporation, Deerfield, IL, USA) (PEN group), or Dianeal (control group) for 12 months, after which both groups continued with Dianeal dialysis for 6 months. Serum and dialysate levels of vascular endothelial growth factor (VEGF), decorin, hepatocyte growth factor (HGF), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), hyaluronan (HA), adiponectin, soluble-intracellular adhesion molecule (s-ICAM), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, and dialysate cancer antigen 125 (CA125), were measured after 12 and 18 months. This paper focuses on results after 12 months, when patients in the PEN group changed to glucose-based PD fluid (PDF).

Results: At the end of 12 months, effluent dialysate levels of CA125, decorin, HGF, IL-6, adiponectin and adhesion molecules were significantly higher in the PEN group compared to controls, but all decreased after patients switched to glucose-based PDF. Macrophage migration inhibitory factor level was lower in the PEN group but increased after changing to glucose-based PDF and was similar to controls at 18 months. Serum adiponectin level was higher in the PEN group at 12 months, but was similar in the 2 groups at 18 months. Body weight, residual renal function, ultrafiltration volume and total Kt/V did not differ between both groups. Dialysate-to-plasma creatinine ratio at 4 h was higher in the PEN group at 12 months and remained so after switching to glucose-based PDF.

Conclusion: Changes in the biomarkers suggest that the PEN PD regimen may be associated with better preservation of peritoneal membrane integrity and reduced systemic vascular endothelial injury.

Keywords: Amino acid; biocompatibility; icodextrin; pH neutral; peritoneal dialysis; peritoneal inflammation.

Figure 1 —

Effect of PEN and glucose-based PD on dialysate CA125 level. Box and whiskers plot showing dialysate CA125 level over time in PEN group (□) and control group (). Data are presented as median (horizontal line within box), 25^th and 75^th percentiles (bottom and top of the box respectively), and the lowest and highest values (bars), excluding outliers (•), the latter defined as values greater than 1.5 times the interquartile range above the third quartile or below the first quartile. Intra- and inter-group comparisons were analyzed with ANOVA. PD = peritoneal dialysis; CA = cancer antigen; PEN = Physioneal (P), Extraneal (E), Nutrineal (N); *** = p<0.001 (12 months vs 18 months in PEN Group); ^# = p<0.05; ^### = p<0.001 (PEN vs control for the same time-point).

Figure 2 —

Effect of PEN and glucose-based PD on dialysate levels of decorin, HGF, and VEGF. Box and whiskers plot showing dialysate levels of (A) decorin, (B) HGF, and (C) VEGF over time in PEN group (□) and control group (). Data are presented as median (horizontal line within box), 25^th and 75^th percentiles (bottom and top of the box respectively), and the lowest and highest values (bars), excluding outliers (•), the latter defined as values greater than 1.5 times the interquartile range above the third quartile or below the first quartile. Intra- and inter-group comparisons were analyzed with ANOVA. PEN = Physioneal (P), Extraneal (E), Nutrineal (N); PD = peritoneal dialysis; HGF = hepatocyte growth factor; VEGF = vascular endothelial growth factor; ^# = p<0.05 (PEN vs control for the same time-point).

Figure 3 —

Effect of PEN and glucose-based PD on dialysate levels of IL-6, MIF, and hyaluronan. Box and whiskers plot showing dialysate levels of (A) IL-6, (B) MIF, and (C) HA over time in PEN group (□) and control group (). Data are presented as median (horizontal line within box), 25^th and 75^th percentiles (bottom and top of the box respectively), and the lowest and highest values (bars), excluding outliers (•), the latter defined as values greater than 1.5 times the interquartile range above the third quartile or below the first quartile. Intra- and inter-group comparisons were analyzed with ANOVA. PEN = Physioneal (P), Extraneal (E), Nutrineal (N); PD = peritoneal dialysis; IL-6 = interleukin-6; MIF = macrophage migration inhibitory factor; HA = hyaluronan; ^# = p<0.05, ^## = p<0.01 (PEN vs control for the same time-point).

Figure 4 —

Effect of PEN and glucose-based PD on dialysate levels of adiponectin, s-ICAM, VCAM-1, and P-selectin. Box and whiskers plot showing dialysate levels of (A) adiponectin, (B) s-ICAM, (C) VCAM-1 and (D) P-selectin over time in PEN group (□) and control group (). Data are presented as median (horizontal line within box), 25^th and 75^th percentiles (bottom and top of the box respectively), and the lowest and highest values (bars), excluding outliers (•), the latter defined as values greater than 1.5 times the interquartile range above the third quartile or below the first quartile. Intra- and inter-group comparisons were analyzed with ANOVA. PEN = Physioneal (P), Extraneal (E), Nutrineal (N); PD = peritoneal dialysis; s-ICAM = soluble-intracellular adhesion molecule; VCAM-1 = vascular cell adhesion molecule-1; ^# = p<0.05; ^## = p<0.01 (PEN vs control for the same time-point).