The size-dependent efficacy and biocompatibility of hyperbranched polyglycerol in peritoneal dialysis

Glucose is a common osmotic agent for peritoneal dialysis (PD), but has many adverse side effects for patients with end-stage renal disease. Recently, hyperbranched polyglycerol (HPG) has been tested as an alternative osmotic agent for PD. This study was designed to further examine the efficacy and biocompatibility of HPG over a range of different molecular weights. HPGs of varying molecular weights (0.5 kDa, 1 kDa, 3 kDa) were evaluated in a preclinical rodent model of PD. HPG PD solutions were standardized for osmolality and compared directly to conventional glucose-based Physioneal™ PD solution (PYS). The efficacy of HPG solutions was measured by their ultrafiltration (UF) capacity, solute removal, and free water transport; biocompatibility was determined in vivo by the histological analysis of the peritoneal membrane and the cell count of detached peritoneal mesothelial cells (PMCs) and neutrophils, and in vitro cytotoxicity to cultured human PMCs. All the different sized HPGs induced higher UF and sodium removal over a sustained period of time (up to 8 h) compared to PYS. Urea removal was significantly higher for 1-3 kDa than PYS, and was similar for 0.5 kDa. Our analyses indicated that the peritoneal membrane exhibited more tolerance to the HPG solutions compared to PYS, evidenced by less submesothelial injury and neutrophil infiltration in vivo, and less cell death in cultured human peritoneal mesothelial cells. Free water transport analysis of HPG indicated that these molecules function as colloids and induce osmosis mainly through capillary small pores. We attribute the differences in the biocompatibility and osmotic activity of different sized HPGs to the differences in the polymer bound water measured by differential scanning calorimetry. These preclinical data indicate that compared to PYS, low MW HPGs (0.5-3 kDa) produces superior fluid and waste removal with better biocompatibility profile, suggesting that they are promising osmotic agents for PD.