A study of the clinical and biochemical profile of peritoneal dialysis fluid low in glucose degradation products

Abstract

Objective: Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy, concerns remain regarding the bioincompatible nature of standard PD fluid (PDF). Short-term studies of new biocompatible PDFs low in glucose degradation products (GDPs) reveal divergent results with respect to peritoneal integrity.

Methods: We studied 125 patients on maintenance PD who were assigned, by simple randomization, to receive either conventional or low-GDP PDF at PD initiation. Parameters of dialysis adequacy and peritoneal transport of small solutes were determined at initiation and after a period of maintenance PD at the time when serum and overnight effluent dialysate were simultaneously collected and assayed for various cytokines, chemokines, adipokines, and cardiac biomarkers. All patients were further followed prospectively for an average of 15 months from the day of serum and effluent collection to determine patient survival and cardiovascular events.

Results: Patients treated with conventional or low-GDP PDF were matched for sex, age, duration of dialysis, dialysis adequacy, and incidence of cardiovascular disease or diabetes. After an average of 2.3 years of PD treatment, the weekly total and peritoneal creatinine clearance, and the total and peritoneal Kt/V were comparable in the groups. However, urine output was higher in patients using low-GDP PDF despite there having been no difference between the groups at PD initiation. Patients using low-GDP PDF also experienced a slower rate of decline of residual glomerular filtration and urine output than did patients on conventional PDF. Compared with serum concentrations, effluent concentrations of tumor necrosis factor α, hepatocyte growth factor, macrophage migration inhibitory factor, interleukins 8 and 6, C-reactive protein, and leptin were found to be higher in both groups of patients after long-term PD, suggesting that the peritoneal cavity was the major source of those mediators. Compared with patients on low-GDP PDF, patients on conventional fluid showed elevated leptin and reduced adiponectin levels in serum and effluent. The effluent concentration of interleukin 8 was significantly lower in patients using low-GDP PDF. The survival rate and incidence of cardiovascular complications did not differ between these groups after maintenance PD for an average of 3.6 years.

Conclusions: It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum.

Figure 1

— Study design and flow diagram. PD = peritoneal dialysis; PET = peritoneal equilibration test; PDF = peritoneal dialysis fluid; GDP = glucose degradation products.

Figure 2

— (A) Mean serum or dialysate concentration, and (B) dialysate-to-serum ratio (expressed as mean ± standard error of the mean) of measured cytokines, growth factors, adipokines, and cardiac biomarkers. The dotted line at the zero mark represents a dialysate-to-serum ratio of unity in the logarithmic scale. IL = interleukin; TNF = tumor necrosis factor α; TGF = transforming growth factor β; HGF = hepatocyte growth factor; NGAL = neutrophil gelatinase-associated lipocalin; MIF = macrophage migration inhibitory factor; VEGF = vascular endothelial growth factor; FGF = fibroblast growth factor; CRP = C-reactive protein; TnT = troponin-T; NT-proBNP = N-terminal prohormone brain natriuretic peptide.

Figure 3

— (A) Kaplan–Meier analysis of cumulative survival in two groups of patients over a mean follow-up period of 15-month after the collection of serum and effluent samples. Causes of death: peritonitis (n = 3), pneumonia (n = 5), acute myocardial infarction (n = 2), biliary sepsis (n = 1), ischemic colitis (n = 1), gastrointestinal infection (n = 1), undetermined (n = 2). (B) Kaplan–Meier analysis of the likelihood a first fatal or nonfatal cardiovascular event (CVS) over a mean 36-month follow-up period after dialysis start in two groups of patients. Patients permanently transferred to alternative renal replacement therapy (including hemodialysis or kidney transplantation) were censored from these survival and cardiovascular outcomes analyses. GDP = glucose degradation products.