Peritoneal Injury by Methylglyoxal in Peritoneal Dialysis

Abstract

Background Peritoneal dialysis (PD) is a common treatment for patients with reduced or absent renal function. Long-term PD leads to peritoneal injury with structural changes and functional decline, such as ultrafiltration loss. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis, a serious complication of PD. Glucose degradation products contained in PD fluids contribute to the bioincompatibility of conventional PD fluids. Methylglyoxal (MGO) is an extremely toxic glucose degradation product. The present study examined the injurious effect of MGO on peritoneum in vivo. Methods Male Sprague–Dawley rats ( n = 6) were administered PD fluids (pH 5.0) containing 0, 0.66, 2, 6.6, or 20 mmol/L MGO every day for 21 days. On day 22, peritoneal function was estimated by the peritoneal equilibration test. Drained dialysate was analyzed for type IV collagen-7S, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF). Histological analysis was also performed. Results In rats receiving PD fluids containing more than 0.66 mmol/L MGO, peritoneal function decreased significantly and levels of type IV collagen-7S and MMP-2 in drained dialysate increased significantly. In the 20-mmol/L MGO-treated rats, loss of body weight, expression of VEGF, thickening of the peritoneum, and formation of abdominal cocoon were induced. MMP-2 and VEGF were produced by infiltrating cells in the peritoneum. Type IV collagen was detected in basement membrane of microvessels. Conclusion MGO induced not only peritoneal injury but also abdominal cocoon formation in vivo. The decline of peritoneal function may result from reconstitution of microvessel basement membrane or neovascularization.

Methylglyoxal‐augmented manuka honey as a topical anti–Staphylococcus aureus biofilm agent: safety and efficacy in an in vivo model

“…This creates difficulty in interpretation of such results because MGO levels among MHs can vary considerably . Similar to previous in vivo studies, tissue damage increased proportionally to MGO concentrations, reflecting its toxic nature. A wealth of in vitro literature currently describes potential mechanisms of MGO toxicity, including free radical production, enzyme dysfunction, oxidative stress, and DNA damage .…”

“…The effects of translation to in vivo models are less clear, with several studies reporting differing outcomes. One such study applying MGO to rat peritoneum found dense adhesion formation and animal death at 20 mmol/L (1.44 mg/mL) levels of MGO . Interestingly, we report no changes to sinus mucosa at similar levels and only microscopic changes at more than double this concentration.…”

“…Human application of these agents is also restricted by concerns over the potential toxicity of MGO on living tissue . Current literature describes toxicity in some studies, whereas others report no deleterious effects . Furthermore, only 1 study has examined the effects of MH when applied to sinonasal mucosa, in which a 33% (wt/vol) MH solution of unspecified MGO content showed no epithelial injury .…”

Effect of Scavenging Circulating Reactive Carbonyls by Oral Pyridoxamine in Uremic Rats on Peritoneal Dialysis

“…This concentration is approximately 10 000 times its concentration in conventional dialysates (13,25). Studies have shown that dialysate loading with up to 20 mmol/L of MG is required to induce full-scale morphological changes in the mesenterium by 21 days of daily dialysis in rats (25)(26)(27). Thus designed our experimental settings induced typical PD-associated morphological alterations of the peritoneum, and oral PM had no effects on pentosidine accumulation in the mesenterium or dialysate effluent despite the fact that PM crossed the peritoneum and amounted to some 20 μg/mL in the dialysate effluent.…”

Matrix metalloproteinase‐2 inhibition by temocapril and its important role in peritoneal transport

“…In patients undergoing PD, MMP‐2 levels in the peritoneal effluent are associated with peritoneal injury and reflect the peritoneal solute transport rate . In experimental models, MMP‐2 levels in drained dialysates became significantly elevated with the development and progression of peritoneal injury, reflected by increased peritoneal solute transport rates . It has been reported that the MMP inhibitor ONO‐4817 prevents peritoneal injury in rats .…”