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BACKGROUND: Glycerol is a low molecular weight solute (MW 92 D) that can be used as an osmotic agent in continuous ambulatory peritoneal dialysis (CAPD). Due to its low molecular weight, the osmotic gradient disappears rapidly. Despite the higher osmolality at the beginning of a dwell, ultrafiltration has been found to be lower for glycerol compared to glucose (MW 180 D) when equimolar concentrations are used. Previous studies have shown glycerol to be safe for long-term use, but some discrepancies have been reported in small solute transport and protein loss. OBJECTIVE: To assess permeability characteristics for a 1.4% glycerol dialysis solution compared to 1.36% glucose. DESIGN: Two standardized peritoneal permeability analyses (SPA), one using 1.4% glycerol and the other using 1.36% glucose, in random order, were performed within a span of 2 weeks in 10 stable CAPD patients. The length of the study dwell was 4 hours. Fluid kinetics and solute transport were calculated and signs of cell damage were compared for the two solutions. SETTING: Peritoneal dialysis unit in the Academic Medical Center, Amsterdam. RESULTS: Median values for the 1.4% glycerol SPA were as follows: net ultrafiltration 251 mL, which was higher than that for 1.36% glucose (12 mL, p < 0.01); transcapillary ultrafiltration rate 2.12 mL/min, which was higher than that for glucose (1.52 mL/min, p = 0.01); and effective lymphatic absorption rate 1.01 mL/min, which was not different from the glucose-based solution. Calculation of peritoneal reflection coefficients for glycerol and glucose showed lower values for glycerol compared to glucose (0.03 vs 0.04, calculated with both the convection and the diffusion models). A marked dip in dialysate-to-plasma ratio for sodium was seen in the 1.4% glycerol exchange, suggesting uncoupled water transport through water channels. Mass transfer area coefficients for urea, creatinine, and urate were similar for both solutions. Also, clearances of the macromolecules beta2-microglobulin, albumin, IgG, and alpha2-macroglobulin were not different for the two osmotic agents. The median absorption was higher for glycerol, 71% compared to 49% for glucose (p < 0.01), as could be expected from the lower molecular weight. The use of a 1.4% glycerol solution during a 4-hour dwell caused a small but significant median rise in plasma glycerol, from 0.22 mmol/L to 0.45 mmol/L (p = 0.02). Dialysate cancer antigen 125 and lactate dehydrogenase (LDH) concentrations during the dwell were not different for both solutions. CONCLUSIONS: These findings show that glycerol is an effective osmotic agent that can replace glucose in short dwells and show no acute mesothelial damage. The higher net ultrafiltration obtained with 1.4% glycerol can be explained by the higher initial net osmotic pressure gradient. This was seen especially in the first hour of the dwell. Thereafter, the osmotic gradient diminished as a result of absorption. The dip in dialysate-to-plasma ratio for sodium seen in the glycerol dwell can also be explained by this high initial osmotic pressure gradient, implying that the effect of glycerol as an osmotic agent is more dependent on intact water channels than is glucose.