Very High Daily Intraperitoneal Doses of Carbonyl Compounds Affect the Morphology, but Not the Exchange Characteristics, of Rat Peritoneum

Abstract

Glucose degradation products (GDP) are carbonyl compounds, that are formed by heat sterilization of conventional peritoneal dialysis (PD) fluids. Carbonyl compounds are known to be toxic in vitro and potentially toxic also in vivo. The aim of this study was to evaluate the effects of daily, short-term exposure of the peritoneum to very high concentrations of GDP in vivo on peritoneal transport parameters and on peritoneal morphology in a well-established rat model of PD. Rats were exposed to three daily intraperitoneal (IP) injections (10 ml) for 9 days of a largely neutral (pH 7.2) PD fluid containing 1.5% glucose and sterilized by filtration, with (n = 8) or without (n = 8) the presence of different carbonyl compounds in concentrations 100 times higher than those reported in commercial PD fluids. Seven rats, not subjected to any exposure, served as controls. After the exposure, the rats were subjected to acute PD in 4-hour dwells. Twenty milliliters of 4% glucose dialysis fluid were instilled into the rat peritoneal cavity. Blood and dialysate samples were taken during the dwell for measurements of dialysate sodium, and for assessments of the mass transfer area coefficient (PS) for glucose and ⁵¹Cr-EDTA and of transperitoneal clearance (Cl) or radiolabelled albumin (RISA). At the end of the dwell, parts of the liver, diaphragm and peritoneum were removed for measurements of tissue cell density and thickness of the submesothelial peritoneal tissue. The exposure of the peritoneum to very high doses of carbonyl compounds did not affect the peritoneal transport of fluid and small solutes significantly, but seemed to slightly reduce lymph flow and albumin clearance out of the peritoneal cavity. Assessed after a hypertonic dwell, and compared to the situation in nontreated rats after the same kind of dwell, there was a significant thinning of the submesothelial tissue, but no difference in tissue cell density. It is concluded that short-term exposure of the peritoneum in vivo to very high doses of GDP resulted in almost no signs of acute toxicity.

Icodextrin Peritoneal Transport In Vitro: Effect of Sodium Deoxycholate, Glucose, and Methylglyoxal

“…Some reports have suggested that the decrease of ultrafiltration during peritoneal dialysis may be related to GDPs (25). Other in vivo investigation showed that elimination of these substances from the conventional acidic fluid did not change ultrafiltration and mass transfer area coefficient for glucose and 51 Cr‐EDTA but decreased these parameters in neutral solution (12). In the present transport analyses, we have studied the direct influence of glucose and methylglyoxal (one of the GDPs forming mainly during the heat sterilization of conventional peritoneal dialysis fluids) on the diffusive permeability of the peritoneum for icodextrin, in the separate experimental series.…”

“…In contrast to the aforementioned studies, GDPs alone caused a significant decrease of thickness of rat submesothelial peritoneal tissue during 9 days. Neither differences in peritoneal cell density nor signs of interstitial fibrosis were observed (12). In other investigation, the number of human peritoneal mesothelial cells in GDP‐treated cultures was reduced by nearly 60% after 36 days (27).…”

“…A few barriers such as capillary endothelium, interstitium, mesothelium, and stagnant fluid layers are involved in the transport of icodextrin and other solutes during peritoneal dialysis (9,10,12–14). In the present study, we have considered the importance of mesothelial and interstitial tissues in this process using the parietal peritoneum.…”

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

“…Such a discrepancy might be due to the study design and the difference in the pH level. Musi et al [36]studied the effect of high concentration GDPs on thickening of the peritoneum, in which the GDP concentrations were 100 times more than conventional PDFs. Surprisingly, the peritoneum exposed to 100 times concentrated GDP solution was thinner than that exposed to non-GDP PDF.…”

Biologic Significance of Reduced Levels of Glucose Degradation Products

“…However, in acute rat experiments, no negative effects of GDPs were observed with respect to peritoneal solute transport [permeability surface area product (PS) for glucose and Cr–ethylenediamine tetraacetic acid (EDTA)] and to UF properties, at least when pH was kept at 5.5 (12). This situation also held true when rats were exposed for 3 weeks to daily injections of PD fluid containing very high concentrations of GDPs (13). The only significant alteration occurring in peritoneal transport properties, after massive, short-term exposure to GDP-containing solutions, was a slight reduction in peritoneal lymph flow.…”