Peritoneal Dialysis Fluid–Induced Angiogenesis in Rat Mesentery Is Increased by Lactate in the Presence or Absence of Glucose

Abstract

Angiogenesis may be an important mechanism behind the functional deterioration of the peritoneum leading to ultrafiltration failure in peritoneal dialysis. The present study was designed to compare the angiogenic properties of lactate-, bicarbonate-, and pyruvate-buffered fluids, evaluated separately with and without glucose. Five different fluids (lactate and bicarbonate with and without 2.5% glucose and pyruvate without glucose) were studied for 5 weeks of twice-daily injections in rats. The respective buffers (40 mmol/l) were adjusted to pH 7.2, and sodium, chloride, calcium, and magnesium were present at standard concentrations. The mesenteric window model, based on observation of the translucent peritoneal sections of the small intestine mesentery, was used for immunohistochemical imaging of microvessels (RECA-1 antigen) and macrophages (ED1 and ED2 antigens). All fluids induced angiogenesis as compared with untreated controls. The lactate-buffered fluids induced larger vascularized zones than did their bicarbonate- and pyruvate-buffered counterparts. Angiogenesis was accompanied by a local recruitment of ED1 macrophages from blood. Addition of glucose to the lactate- and bicarbonate-buffered fluids did not seem to alter their pro-angiogenic properties. In conclusion, intraperitoneal exposure to lactate buffer, compared with bicarbonate, stimulates angiogenesis in the presence or absence of glucose.

Effect of the Dialysis Fluid Buffer on Peritoneal Membrane Function in Children

“…Superfusion of rat peritoneum with L-PDF caused a transient increase in arteriolar flow and capillary recruitment, whereas B-PDF did not affect the hemodynamic parameters (31). In rats, two time per day intraperitoneal injections of L-PDF over 5 weeks induced more peritoneal neoangiogenesis than B-PDF (19). These experimental findings suggest mechanisms for the observed differences in ultrafiltration capacity and creatinine and phosphate transport over time with B-PDF and L-PDF in our children.…”

“…Lactate, particularly at low pH, has detrimental effects on peritoneal mesothelial and leukocyte function (14,15). At neutral pH, lactate still impairs human peritoneal mesothelial cell viability and function, whereas cellular functions are preserved with bicarbonate buffer (16)(17)(18)(19). Thus, the PD buffer choice may impact on peritoneal membrane morphology and function.…”

Buffer-dependent regulation of aquaporin-1 expression and function in human peritoneal mesothelial cells

“…We assessed the relevance of buffer choice of biocompatible PDFs. Earlier work demonstrated a potential impact of buffer substance on mesothelial cells and peritoneal macrophages, suggesting some cytotoxicity as well as profibrotic and proangiogenic actions of lactate compared with bicarbonate [24,25]. The relevance of these effects, however, was questionable in view of the marked overall toxicity of conventional GDPcontaining solutions [1][2][3].…”

Peritoneal Inflammation after Twenty-Week Exposure to Dialysis Solution: Effect of Solution versus Catheter–Foreign Body Reaction

“…Lactate buffer (18), low pH (19), and GDP (20) all are thought to contribute to the inflammatory changes observed in PD (21). The BIC solution has a normal pH, bicarbonate buffer, and low GDP.…”