**Abstract**

Peritoneal dialysis (PD) is a type of renal replacement therapy which is based on the use of peritoneum, which acts as a semipermeable membrane with diffusion and convection. Long term use can produce structural and functional changes of the membrane by the activation of the resident fibroblasts and infiltrating inflammatory cells, mesothelial to mesenchymal transition, further leading to fibrosis, angiogenesis and ultrafiltration failure. This is due to use of bioincompatible fluids, frequent peritoneal inflammation, uremic milieu and other multiple factors. The peritoneal fibrosis has two parts: fibrosis and inflammation, which induces each other via TGF/SMAD pathway and IL-6 signaling, respectively. The advent of newer biocompatible fluids along with additives has significantly reduced the production of glucose degradation products (GDPs). In addition, the identification of the biomarkers in peritoneal effluent is necessary, which, after being correlated with peritoneal biopsy, may help us to guide future studies and assessment of the efficacy of therapeutic interventions. Various interventions are being tried based on experimental studies from animal models, pharmacology and gene therapy with promising results, with new insights in near future. This article reviews the main aspects associated with the functional and structural alterations related to PD and discusses interventions whereby we may prevent them to preserve the peritoneal membrane.

**Keywords:** peritoneal dialysis, ultrafiltration, encapsulating peritoneal sclerosis, mesothelial to mesenchymal transition (MMT), VEGF (vascular endothelial growth factors), GDP (glucose degradation products)

## **1. Introduction**

Peritoneal dialysis (PD) is a life-sustaining therapy used by >100,000 patients with ESRD worldwide, accounting for approximately 10 to 15% of the dialysis population [1]. Despite these benefits, only a small number of dialysis patients receive PD, in Europe about 13% and in the USA about 10% and 6% in India [2, 3]. The major obstacles for a successful long-term PD are infections and the deleterious functional alterations in the peritoneal membrane following prolonged exposure to dialysis fluids; which is responsible for increased morbidity and mortality. These alterations, such as progressive fibrosis and vasculogenesis, leading to increased solute transport and ultrafiltration (UF) failure, are seen in more than 50% of patients on PD.

Rippe proposed the existence of three pores of different sizes in peritoneal membrane: a large pore of 100–200 Å corresponding to interendothelial cell clefts allowing transport of large molecular weight solutes; a small pore of 40–60 Å, which allows for transport of water and low molecular weight (LMW)solutes and an ultrasmall pore of 4–6 Å that allows for the passage of only water.
