Advanced glycation end-products in the peritoneal fluid and in the peritoneal membrane of continuous ambulant peritoneal dialysis patients

Abstract

In patients on continuous ambulant peritoneal dialysis (CAPD) treatment, the peritoneal membrane is continuously exposed to the high glucose concentration contained in the dialysate. This may lead to the local generation of advanced glycation end-products (AGEs). To test this hypothesis we evaluated the plasma and dialysate AGE concentrations in five CAPD patients. The dialysate was measured after a 1 h and after a 12 h dwell time. Additionally, in two patients an immunohistochemical investigation of the peritoneal membrane for AGE was performed. For the determination of AGE an ELISA using a polyclonal antibody against AGE bovine serum albumin was used; the immunohistochemical staining was performed using the streptavidin-biotin complex method. We found only low concentrations of AGE in the dialysate after a 1 h dwell time; after 12 h, however, the dialysate AGE was even greater than the plasma concentration. In both peritoneal specimens we found positive staining for AGE in the interstitium of the mesothelial layer. The dialysate AGE contained a high proportion of high-molecular-weight AGE proteins and low-molecular-weight AGE was found to be in the same concentration range as the total serum AGE. We conclude that there is local generation of AGE in the peritoneal membrane and a 'washing out' of AGE from the peritoneal membrane during longer dwell times. We speculate that the accumulation of AGE might lead to some of the functional and morphological alterations observed after long-term CAPD.

Development and validation of an HPLC method to quantify 3,4‐dideoxyglucosone‐3‐ene in peritoneal dialysis fluids

“…In comparison to sugars, GDPs have a much higher reactivity towards proteins (glycation), leading to the formation of advanced glycation end-products (AGEs) (Tauer et al, 2001;Millar et al, 1998;Schalkwijk et al, 1999). AGEs accumulate in the peritoneum of patients undergoing CAPD, a process which correlates with the progression of interstitial fibrosis and vascular sclerosis (Mahiout et al, 1996;Nakayama et al, 1997;Honda et al, 1999). Furthermore, GDPs and heat sterilized PD fluids showed a cytotoxic activity against peritoneal mesothelium cells in vitro (Witowski et al, 2000).…”

Induction of Metallothionein in Mesothelial Cells by Zinc

“…For example, advanced glycation end (AGE) products perform their receptor‐mediated effects by a ROS‐dependent activation of mitogen‐activated protein kinase (12,13). PD causes increased burden of AGEs to the peritoneum (14–18). Induction of intracellular antioxidative molecules, like MT, can offer some prevention against the damages related to AGE (19).…”

Effects of Neutral pH and Reduced Glucose Degradation Products in a New Peritoneal Dialysis Solution on Morphology of Peritoneal Membrane in Rats

“…More recently, Morgan et al [30]have reported that GDPs, especially formaldehyde and 3,4-di-deoxyglucosone-3-ene (3,4-DGE), impair the mesothelial repair, independent of effects on cell viability or glucose concentration in a scratch-wounding model. Moreover, a few kinds of GDPs accelerate formation and accumulation of AGEs, followed by dysfunction of the peritoneal membrane in PD therapy [3, 5]. …”

“…Although the acute toxicity of GDPs contained in PD solutions is limited, a large body of data has demonstrated that exposure of the peritoneal membrane to a low level of GDPs over a long period results in structural and functional changes. Moreover, it has been reported that GDPs in the peritoneum contribute to the formation of advanced glycation end-products (AGEs), which affect the morphology and function of the peritoneum [3, 4]. The accumulation of AGEs accelerates peritoneal permeability and thus causes an ultrafiltration failure [5].…”