Glucose Degradation Products (GDP’s) and Peritoneal Changes in Patients on Chronic Peritoneal Dialysis: Will New Dialysis Solutions Prevent these Changes?

Abstract

As peritonitis rates are declining, the rate of technique failure due to ultrafiltration failure and inadequate solute removal is becoming more important. The failure of the peritoneal membrane to provide adequate dialysis increases with longer duration on PD and correlates with the structural changes in the peritoneal membrane. The exact mechanism responsible for these structural changes is unclear. Conventional PD fluids with glucose as the osmotic agent and more importantly the glucose degradation products (GDP) generated during the heat sterilization of these solutions seems to be responsible for inducing many of these changes in the peritoneum. GDP's in addition to causing structural and functional alterations of the peritoneal cells is also a leading cause of advanced glycation end-products (AGE) production. There is evidence to suggest that the GDP's and AGE's are not limited to the peritoneal cavity and the membrane. They have been shown to get deposited in the vascular walls. In addition they also interact with receptors on endothelial cells and smooth muscle. Thus they could contribute to the vascular dysfunction similar to that seen in diabetes. Formation of GDP's can be reduced and even be avoided with the use of newer "biocompatible" solutions by sterilizing the glucose and the buffer in separate chambers. These newer solutions have been shown to have several local and systemic advantages over the conventional PD solutions. It remains to be seen whether their chronic use from the start of peritoneal dialysis will prevent the development of peritoneal damage thus allowing these patients to remain on this modality for longer periods.

Peroxisome Proliferator-Activated Receptor-γ Agonists Diminish Peritoneal Functional and Morphological Changes Induced by Bioincompatible Peritoneal Dialysis Solution

“…Therefore, although fibrosis also occurs in patients in response to a variety of other injuries, including peritonitis, uremia and chronic inflammation [4] , conventional PD solutions may play a major role in causing peritoneal fibrosis. Because of this, a new generation of bicarbonate/lactate-buffered PD solutions with a physiological pH and low GDPs has been developed, and these have been reported to improve mesothe-lial cell proliferation and viability in vitro [5] but may not totally eliminate the effects of high glucose concentration on the peritoneal tissue [6] . Additionally, these new solutions are not yet available in many countries, including most developing countries with a large portion of the world's PD population [7] .…”

The dipeptide alanyl-glutamine ameliorates peritoneal fibrosis and attenuates IL-17 dependent pathways during peritoneal dialysis

“…1 PD is based on the ability of the peritoneum to function as a dialyzing membrane, allowing the exchange of solutes and waste products between the blood stream and the peritoneal dialysis fluid (PDF) instilled through a permanent catheter. [2][3][4][5][6] This home-based treatment preserves the patient's residual renal function and provides better quality of life while ensuring equivalent patient survival compared with hemodialysis. Unfortunately, long-term PD is associated with the development of functional and structural alterations to the peritoneal membrane.…”

Ongoing exposure to peritoneal dialysis fluid alters resident peritoneal macrophage phenotype and activation propensity

“…both approaches indicate intriguing opportunities to develop novel techniques specifically 491 targeting peritoneal MΦres. This seems in contrast to the commonly held believe that the constituents of PD fluid, in 504 particular lactate, glucose-degradation-products (GDP) and low pH, are instrumental in 505 driving PD related pathology (69,70). However, our data is in line with a recent report 506 investigating the use of so-called biocompatible PD fluid in patients.…”