Review Article

Regulation of Synthesis and Roles of Hyaluronan in Peritoneal Dialysis

Table 1

Summary of studies discussed in the text.
(a)

StudyOrganismHA concentration and applicationHA Effects on UFOther HA Effects

Wang et al., 1997 [102]RatSingle 4 h dwell with HA 0.005% and 0.01%Increased UF, mainly through decreased peritoneal fluid absorptionIncreased peritoneal clearance of urea

Wang et al., 1999 [103]RatSingle 4 h dwell with HA 0.01%Increased net UF, mainly by decreased peritoneal fluid absorptionIncreased peritoneal clearance of urea. HA may prevent decreased net UF caused by an increased dialysate fill volume

Wang et al., 1999 [104]RatSingle 4 h dwell with HA in various concentrations (0.01–0.5%) and molecular weights (MW; 85 kDa–4 MDa)Increased size and concentration of HA resulted in decreased peritoneal fluid absorption. Low concentrations of high MW HA might decrease transcapillary UF rate

Połubinska et al., 2000 [97] RatHigh MW HA 10 mg/dL twice daily for 4 weeksTotal drained volume in HA group was significantly higher (positive net UF in HA group versus negative net UF in control group)Clearance of total protein and albumin tended to be lower; clearance of urea and creatinine tended to be higher. Significantly decreased percentage of IP neutrophils and levels of MCP-1 and TNF-

Guo et al., 2001 [101]Rat0.025% HA in a 4 h dwell for 1 weekDecreased peritoneal fluid absorption (similar to native animals)Significant decrease in protein transportation rate

Breborowicz et al., 2001 [100]RatOne infusion of 10 mg/dL HA for a 1–8 h dwellNet UF was significantly greater at 4, 6, and 8 h compared to controlsDuring 8 h exchange, creatinine clearance was significantly higher and total protein clearance significantly lower. After 8 h, 25.7% HA absorbed from peritoneal cavity and peritoneal tissue HA increased to 117%; plasma HA levels increased to 435%. Plasma HA normalized within 24 h in uremic and nonuremic animals

Breborowicz et al., 2001 [108]RatAcute peritonitis induced with lipopolysaccharide; HA at 10 mg/dL; 4 and 8 h dwellSignificant reduction in loss of UFSignificantly increased creatinine clearance. Greater dialysate interferon--levels and less pronounced elastase levels

Moberly et al., 2003 [109]HumanProspective randomized crossover study with 6 h application of Dianeal and Dianeal containing HA (0.1 and 0.5 g/L). 2-week washout analysed after exchangeNo significant differences in net UF or peritoneal volume profilesNo adverse effects of HA

Breborowicz et al., 2004 [64]HumanOne 6 h dwell with 13.6 g/L glucose-based solution ±0.1 and 0.5 g/L of exogenous high MW HA. 2-week application intervals Significant increased concentration of nitrites in HA 0.5 g/L supplemented dialysate. No difference in concentrations of MCP-1, s-ICAM1, EGF, and fibronectin

(b)

StudyOrganismPD regime (not HA)Other HA effects

Wieczorowska-Tobis et al., 2004 [111]Rat2 daily injections of 4.25% glucose-containing PDF for 6 weeks. PDFs tested: CAPD3 (single-chamber bag, low pH, and high GDP), CAPD3 pH 7.4 (single-chamber bag, neutral pH, and high GDP), CAPD3 balance (double-chamber bag, neutral pH, and low GDP)Reduced concentrations of protein and HA in dialysate. Introduced PD fluids with physiologic pH and low GDP level producing less irritation to the peritoneal membrane, better preserving its structural integrity

Zareie et al., 2005 [112]RatUraemic and control rats received daily 10 mL conventional glucose containing PD fluid, via peritoneal catheters during a 6-week periodIncreased MCP-1 and HA levels in peritoneal lavage fluid

Flessner et al., 2006 [113]RatFiltered solutions with 4% N-acetylglucosamine (NAG) or 4% glucose (G) IP injected daily in 2–300 g rats compared with controls (C). At 2 months, transport studies using chamber affixed to parietal peritoneum determined small-solute and protein mass transfer, osmotic filtration, and hydraulic flowTissue analysis showed treatment effects on tissue HA (microg/g: C, 962 ± 73; G, 1,169 ± 69; NAG, 1,428 ± 69; and < 0.05) and collagen (microg/g: C, 56.9 ± 12.0; G, 107 ± 12; NAG, 97.6 ± 11.4; and < 0.05) but not sulfated glycosaminoglycan

Schilte et al., 2009 [114]RatUsed 10 mL PD fluid daily, ±unfractionated heparin, or low MW heparin in PD fluid (1 mg/10 mL) IP via mini access port, untreated control rats. At 5 weeks, peritoneal transport was tested; tissues and peritoneal leukocytes were sampledIncreased peritoneal cell influx and HA production () as well as an exchange of mast cells and eosinophils for neutrophils after PD treatment observed in PD rats

Loureiro et al., 2010 [115]RatOver 5 weeks, rats instilled daily using PD fluid ± BMP-7rhBMP-7-treatment did not significantly affect any of these processes induced by PD fluid exposure, except for a tendency to reduce HA production ( = 0.054), suggesting decreased peritoneal fibrosis

Rosengren et al., 2013 [119]HumanAfter 8 weeks PD, interstitial fluid (IF) from peritoneum was isolated via centrifugation; IF and plasma were analyzed for cytokine content and colloid osmotic pressureIF colloid osmotic pressure decreased significantly in PD group, while collagen and HA content was increased

Kinashi et al., 2013 [120]HumanRole of the lymphangiogenesis mediator VEGF-C analysed in human dialysate effluents, peritoneal tissues, and HPMCsPeritoneal tissue from patients with UF failure expressed higher levels of VEGF-C, LYVE-1, and podoplanin mRNA and contained more lymphatic vessels than tissue from patients without UF failure