Exosomes: The New Mediator of Peritoneal Membrane Function.

Fibrosis and angiogenesis are the most common processes that result in progressive peritoneal tissue remodeling and, eventually, peritoneal membrane dysfunction. The role of exosomes, which contributes to intercellular communication, in these processes has been neglected. Various biomolecules, including DNA, mRNA, proteins, lipids, and particular certain miRNAs, can be transferred by exosomes to local, neighboring and distal cells. Upon stimulation by cytokines or other microenvironment stimuli, donor cells release a mass of exosomes to peritoneal mesothelial cells, further affecting fibrosis and angiogenesis. This important exosomes-mediated intracellular communication is thought to regulate peritoneal membrane function. Understanding the molecular mechanisms of these processes, targeting changes in exosomes and regulating exosomal miRNAs will advance therapeutic methods for protecting peritoneal membrane function.

Ionic conductivity of peritoneal dialysate: a new, easy and fast method of assessing peritoneal membrane function in patients undergoing peritoneal dialysis.

BACKGROUND: Peritoneal membrane function can be assessed using the peritoneal equilibration test (PET) and similar tests, but these are almost always complicated to use, require a considerable amount of working time and their results cannot always be easily interpreted. Ionic conductivity is a measure of the ability of an electrolyte solution to conduct electricity. We tested the hypothesis that the ionic conductivity of peritoneal dialysate can be used to evaluate peritoneal membrane function in peritoneal dialysis patients. METHODS: We measured the ionic conductivity and classic biochemical parameters of peritoneal dialysate in 69 patients during a modified PET and compared their ability to evaluate peritoneal membrane function and to diagnose ultrafiltration failure (UFF). RESULTS: Ionic conductivity was correlated well with classical parameters of peritoneal transport as glucose reabsorption of glucose (D/D0: r(2) = 0.62, P < 0.0001) and creatinine transport (D/PCreat: r(2) = 0.72, P < 0.0001). Twelve patients (17%) experienced UFF and, in them, the ionic conductivity area under the receiver-operating characteristic curve was 0.91 (95% confidence interval: 0.81-0.96) with sensitivity of 1.00 and specificity of 0.84 at a cut-off value of 12.75 mS/cm. CONCLUSIONS: These findings indicate that the ionic conductivity of peritoneal dialysate can be used as a new screening tool to evaluate peritoneal membrane function.

International Icodextrin Use and Association with Peritoneal Membrane Function, Fluid Removal, Patient and Technique Survival.

Background: Icodextrin has been shown in randomized controlled trials to benefit fluid management in peritoneal dialysis (PD). We describe international icodextrin prescription practices and their relationship to clinical outcomes. Methods: We analyzed data from the prospective, international PDOPPS, from Australia/New Zealand, Canada, Japan, the United Kingdom, and the United States. Membrane function and 24-hour ultrafiltration according to icodextrin and glucose prescription was determined at baseline. Using an instrumental variable approach, Cox regression, stratified by country, was used to determine any association of icodextrin use to death and permanent transfer to hemodialysis (HDT), adjusted for demographics, comorbidities, serum albumin, urine volume, transplant waitlist status, PD modality, center size, and study phase. Results: Icodextrin was prescribed in 1986 (35%) of 5617 patients, >43% of patients in all countries, except in the United States, where it was only used in 17% and associated with a far greater use of hypertonic glucose. Patients on icodextrin had more coronary artery disease and diabetes, longer dialysis vintage, lower residual kidney function, faster peritoneal solute transfer rates, and lower ultrafiltration capacity. Prescriptions with or without icodextrin achieved equivalent ultrafiltration (median 750 ml/d [interquartile range 300-1345 ml/d] versus 765 ml/d [251-1345 ml/d]). Icodextrin use was not associated with mortality (HR=1.03; 95% CI, 0.72 to 1.48) or HDT (HR 1.2; 95% CI, 0.92 to 1.57). Conclusions: There are large national and center differences in icodextrin prescription, with the United States using significantly less. Icodextrin was associated with hypertonic glucose avoidance but equivalent ultrafiltration, which may affect any potential survival advantage or HDT.