Intermittent hypoxia in rat enhancing peritoneal membrane thickening through HIF-1α-induced cytokines in peritoneum.

BACKGROUND: Due to the high prevalence of both obstructive sleep apnea syndrome (OSA) and end-stage renal disease (ESRD), the co-existence of both conditions in peritoneal dialysis is demonstrated. Because OSA-induced chronic intermittent hypoxia is well-known, the hypoxia might worsen peritoneal membrane. OBJECTIVE: We tested the influence of chronic intermittent hypoxia upon peritoneal membrane in a Sprague-Dawley rat model. METHODS: Normal saline or 3.86% glucose peritoneal dialysis fluid (PDF) were intra-peritoneally administered twice a day as negative (NSS group) and positive controls (PDF group), respectively. Intermittent hypoxia was induced by using a hypoxic chamber with 10% O2 for 8 hours a day plus twice-daily NSS injection (IH group). RESULTS: At 12 weeks of the experiments, high serum TNF-α and IL-6 (but not IL-10) with normal renal and liver functions were demonstrated in the IH group (but not the PDF group). In parallel, local cytokines (TNF-α, IL-6, and IL10 in peritoneal membrane) and peritoneal membrane thickness were increased whereas peritoneal membrane hypoxia (hypoxyprobeTM and hypoxia-inducible factor-1α; HIF-1α) was induced in both PDF and IH groups (more prominent in the PDF group). However, the increased vascular density in submesothelial area was established only in the PDF group. CONCLUSION: Intermittent hypoxia model induced local peritoneal membrane inflammation and enhanced peritoneal membrane thickness, at least in part, through a mechanism of hypoxia-induced HIF-1α. Although peritoneal membrane alterations from PDF were more prominent than intermittent hypoxia, the combination between intermittent hypoxia with PDF utilization might facilitate peritoneal membrane failure, which will need more study.

Overnight mesothelial cell exfoliation: a magic tool for predicting future ultrafiltration failure in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Continuous exposure of the peritoneal membrane to dialysis solutions during long-term dialysis results in mesothelial cell loss, peritoneal membrane damage, and thereby, ultrafiltration (UF) failure, a major determinant of mortality in patients on continuous ambulatory peritoneal dialysis (CAPD). Unfortunately, none of tests available today can predict long-term UF decline. Here, we propose a new tool to predict such a change. PATIENTS AND METHODS: Mesothelial cells from 8-hour overnight effluents (1.36% glucose dialysis solution) were harvested, co-stained with cytokeratin (a mesothelial marker) and TUNEL (an apoptotic marker), and were counted using flow cytometry in 48 patients recently started on CAPD. Adequacy of dialysis, UF, nutrition status, dialysate cancer antigen 125 (CA125), and a peritoneal equilibration test (3.86% glucose peritoneal dialysis solution) were simultaneously assessed and were re-evaluated 1 year later. RESULTS: The numbers of total and apoptotic mesothelial cells were 0.19 +/- 0.19 million and 0.08 +/- 0.12 million cells per bag, respectively. Both numbers correlated well with the levels of end dialysate-to-initial dialysate (D/D(0)) glucose, dialysate-to-plasma (D/P) creatinine, and sodium dipping. Notably, the counts of cells of both types in patients with diabetes or with high or high-average transport were significantly greater than the equivalent counts in nondiabetic patients or those with low or low-average transport. A cut-off of 0.06 million total mesothelial cells per bag had sensitivity of 1 and a specificity of 0.75 in predicting a further decline in D/D(0) glucose and a sensitivity of 0.86 and a specificity of 0.63 to predict a further decline in UF over a 1-year period. In contrast, dialysate CA125 and other measured parameters had low predictive values. CONCLUSIONS: The greater the loss of exfoliated cells, the worse the expected decline in UF. The ability of a count of mesothelial cells to predict a future decline in UF warrants further investigation in clinical practice.