Peritoneal Dialysis Induces Alterations In The Transcriptome Of Peritoneal Cells Before Detectible Peritoneal Functional Changes

Long-term peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane. Inflammation may be the key moment and consequently fibrosis, the end result of chronic inflammatory reaction. The objective of the study was to identify genes involved in peritoneal alterations during PD by comparing transcriptome of peritoneal cells in short- and long-term PD patients. Peritoneal effluent of the long-dwell of stable PD patients was centrifuged to obtain peritoneal cells. Gene expression profiling of peritoneal cells using microarray between short- and long-term PD patients was compared. Based on microarray analysis 31 genes for RT-qPCR validation were chosen. A 4-hour peritoneal equilibration test (PET) was performed on the day after the long dwell. Transport parameters and proteins appearance rates were assessed. Genes involved in the immune system process, immune response, cell activation, leuko- and lymphocyte activation were found to be substantially up-regulated in the long-term group. RT-qPCR validation showed higher expression of CD24 (CD24 molecule), LY9 (lymphocyte antigen 9 ), TNFRSF4 (tumor necrosis factor receptor superfamily, member 4), CD79A (CD79a molecule, immunoglobulin-associated alpha), CCR7 (chemokine (C-C motif) receptor 7), CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) and IL2RA (interleukin 2 receptor, alpha) in long-term PD patients, CD24 having the best discrimination ability between short- and long-term treatment. A relationship between CD24 expression and genes for collagen and matrix formation was shown. Activation of CD24 provoked by pseudohypoxia due to extremely high glucose concentrations in dialysis solutions might play the key role in the development of peritoneal membrane alterations. An observational,prospective, cross-sectional cohort study was performed to compare expression profiles of peritoneal cells of patients with short-term (n=20) and long-term peritoneal dialysis (PD) (n=13). Short-term is defined as patients with a PD duration between 0 and 24 months and long-term patients with a PD duration of ≥ 25 months. Peritoneal effluent of the long-dwell (median 9, range 8-13 hours) was centrifuged to obtain peritoneal cells. As microarray platform, Illumina HumanHT 12 v4.0 Expression BeadChips (Illumina) was used. Classification of clinical samples.