Determinants of Peritoneal Membrane Function Over Time

Abstract

Changes to peritoneal membrane function over time result in the development of ultrafiltration failure in a proportion of PD patients and pose a risk for the rarer condition of encapsulating peritoneal sclerosis. These changes are characterized by an increase in the transport rate for small solutes owing to increased vascularity and/or peritoneal blood flow and in more severe cases a reduction in the osmotic conductance of the membrane that likely reflects progressive fibrosis. Both of these processes are preceded by exposure of the membrane to glucose when using conventional dialysis solutions, although this usually is necessitated and likely exacerbated by loss of residual renal function and recurrent peritonitis. Mediators of membrane injury and thus potential biomarkers include inflammatory cytokines, notably local interleukin-6 production, which also appears to determine solute transport characteristics at the start of peritoneal dialysis, local production of vascular endothelial growth factor, and transforming growth factor β-associated epithelial to mesenchymal transition of the mesothelium leading to membrane fibrosis. Low glucose degradation product solutions may ameliorate the mesothelial injury associated with high glucose exposure, but evidence that they prevent or delay changes in membrane function over time is lacking. In the meantime, avoidance of excessive glucose exposure, preservation of residual renal function, and prevention of peritonitis remain the most logical treatment strategies for this problem.