Glucose Degradation Products in Peritoneal Dialysis: From Bench to Bedside

Jörres, Achim

doi:10.1159/000070993

Cited by 16 publications

(10 citation statements)

References 23 publications

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“…The GDPs in conventional PDF cause mesothelial injury and reduce mesothelial regeneration, hence predisposing the patient to peritoneal fibrosis (15). In addition, accumulation of AGEs in the peritoneal tissue correlates with the development of severe interstitial fibrosis and microvascular sclerosis in PD (2,16).…”

Section: Discussionmentioning

confidence: 99%

A Study of the Clinical and Biochemical Profile of Peritoneal Dialysis Fluid Low in Glucose Degradation Products

et al. 2012

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♦ 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.

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Section: Discussionmentioning

confidence: 99%

A Study of the Clinical and Biochemical Profile of Peritoneal Dialysis Fluid Low in Glucose Degradation Products

et al. 2012

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“…These fluids contain GDPs that are formed primarily during heat sterilization [20]. Several of these products have been identified and quantified [21] and, recently, 3,4‐DGE has been found to be the main candidate responsible for the clinical biocompatibility caused by conventional PDF [22]. Evidence has suggested that the mesothelial toxicity of PDF is related primarily to GDPs and not to glucose per se [23].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of receptors for advanced glycation end-products in peritoneal mesothelial cells exposed to glucose degradation products

Lai

Leung

Chan

et al. 2004

Clinical and Experimental Immunology

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SUMMARYAutoclaving peritoneal dialysate fluid (PDF) degrades glucose into glucose degradation products (GDPs) that impair peritoneal mesothelial cell functions. While glycation processes leading to formation of advanced glycation end-products (AGE) were viewed commonly as being mediated by glucose present in the PDF, recent evidence indicates that certain GDPs are even more powerful inducers of AGE formation than glucose per se . In the present study, we examined the expression and modulation of AGE receptors on human peritoneal mesothelial cells (HPMC) cultured with GDPs, conventional PDF or PDF with low GDP content. HPMC cultured with GDPs differentially modulated AGE receptors (including RAGE, AGE-R1, AGE-R2 and AGE-R3) expression in a dose-dependent manner. At subtoxic concentrations, GDPs increased RAGE mRNA expression in HPMC. 2-furaldehyde (FurA), methylglyoxal (M-Glx) and 3,4-dideoxy-glucosone-3-Ene (3,4-DGE) increased the expression of AGE-R1 and RAGE, the receptors that are associated with toxic effects. These three GDPs up-regulated the AGE synthesis by cultured HPMC. In parallel, these GDPs also increased the expression of vascular endothelial growth factor (VEGF) in HPMC. PDF with lower GDP content exerted less cytotoxic effect than traditional heat-sterilized PDF. Both PDF preparations up-regulated the protein expression of RAGE and VEGF. However, the up-regulation of VEGF in HPMC following 24-h culture with conventional PDF was higher than values from HPMC cultured with PDF containing low GDP. We have demonstrated, for the first time, that in addition to RAGE, other AGE receptors including AGE-R1, AGE-R2 and AGE-R3 are expressed on HPMC. Different GDPs exert differential regulation on the expression of these receptors on HPMC. The interactions between GDPs and AGE receptors may bear biological relevance to the intraperitoneal homeostasis and membrane integrity.

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“…Concentrations of 3-deoxyglucosone, acetaldehyde, formaldehyde, methylglyoxal, glyoxal, furfural and 5-hydroxymethyl-furfural are significantly reduced when compared to standard PD fluids [65,67]. A summary of the numerous in vitro and in vivo experiments describing the beneficial effects of these new solutions is beyond the scope of this paper but can be found in several recent reviews [28,33,51,60,[68][69][70].…”

Section: Dialysate Glucose and Gdpsmentioning

confidence: 99%

Volume Control in Peritoneal Dialysis Patients: Role of New Dialysis Solutions

Lameire¹

2004

Blood Purif

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This paper reviews the most recent clinical data on the volume status of long-term peritoneal dialysis (PD) patients. It appears that many PD patients are volume overloaded, associated with a high prevalence of hypertension and left ventricular hypertrophy. In the presence of the poor results in patients with peritoneal ultrafiltration, the introduction of the polyglucose solution, icodextrin, has ameliorated volume control in some of these patients. In a second part of the review, some of the structural and functional alterations in the peritoneal membrane and the role of glucose degradation products (GDP) in the commonly used dialysates as well as the resulting formation of advanced glycation end products are described. The introduction of low GDP-containing solutions at normal pH has at least in experimental models of PD attenuated the hemodynamic changes observed with the classical solutions. The solutions at normal pH containing either bicarbonate or a mixture of bicarbonate/lactate were clinically associated with less inflow pain.

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Glucose Degradation Products in Peritoneal Dialysis: From Bench to Bedside

Cited by 16 publications

References 23 publications

A Study of the Clinical and Biochemical Profile of Peritoneal Dialysis Fluid Low in Glucose Degradation Products

A Study of the Clinical and Biochemical Profile of Peritoneal Dialysis Fluid Low in Glucose Degradation Products

Differential expression of receptors for advanced glycation end-products in peritoneal mesothelial cells exposed to glucose degradation products

Volume Control in Peritoneal Dialysis Patients: Role of New Dialysis Solutions

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