Phenotype and genotype: perspectives for peritoneal dialysis patients.

Peritoneal dialysis (PD) is currentlyusedon 15%of the worldwide dialysis population. Recent improvements in connectology and antibiotics management have led to a dramatic reduction in the rate and consequences of peritonitis in PD patients. Deterioration of membrane permeability, with modifications in the transport of small solutes across the peritoneal membrane (PM) and loss of ultrafiltration (UF), is the most frequent abnormality in long-term PD patients, and the main reason for technical failure. A better understanding of the mechanisms and determinants of the small solute transport and UF is now essential to achieve long-term preservation of the PM together with improvements in patient morbidity and mortality. The transport of solutes and water across the PM occurs through three types of pores located in the capillary endothelium [1]. The ‘small pores’ (radius 40–50 Å), which correspond to the clefts located between endothelial cells, account for 95% of the hydraulic conductance (UF coefficient, LpS). A second population of pores, the ‘large pores’ (radius 250 Å), thought to correspond to the venular interendothelial gaps, accounts for 5% of the UF coefficient. These pores are involved in the transport of macromolecules and mediate an important part of UF via fluid convection from blood to the peritoneal cavity. The third population of pores consists of water-specific, ‘ultrasmall pores’ located in the endothelial cells; these correspond to aquaporin-1 (AQP1). Although they account for only 1–2% of the hydraulic conductance, ultrasmall pores reject solutes and facilitate the transport of water during crystalloid osmosis. Data obtained on the AQP1 mouse model have confirmed that ultrasmall pores do mediate 50% of the UF, as well as the ‘sodium sieving’, i.e. the rapid fall in dialysate sodium concentration during a dwell with hypertonic glucose [2]. In this editorial comment, we will review the clinical tools available to assess the transport properties of the PM at the start of PD, corresponding to a given phenotype. We will next summarize what is known about the clinical determinants of individual variability in baseline peritoneal transport. Based on the fact that clinical factors only account for a small part of the variability, we will then discuss how genetic factors may contribute to the baseline transport—opening a perspective for genotype—phenotype correlations in PD.