Dialysis solution containing hyaluronan

Effect on peritoneal permeability and inflammation in rats

Alicja Połubinska, Krzystof Pawlaczyk, Małgorzata Kuzlan-Pawlaczyk, Katarzyna Wieczorowska-Tobis, Chi Chen, James B. Moberly, L. Martis, Andrzej Brȩborowicz, Dimitrios G. Oreopoulos

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Background. Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks. Methods. Wistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment. Results. After four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P <0,001; 33% lower for total protein, P <0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P <0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 ± 6.7 vs. 22.8 ± 9.5%, P <0.01) and lower levels of the cytokines, tumor necrosis factor-α (11.2 ± 14.7 vs. 42.3 ± 35.3 pg/mL, P <0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 ± 86.5 vs. 402.4 ± 258.3 pg/mL. P <0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P <0.01) than tissue from control animals. Conclusions. The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.

Original languageEnglish (US)
Pages (from-to)1182-1189
Number of pages8
JournalKidney International
Volume57
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Dialysis Solutions
Hyaluronic Acid
Permeability
Inflammation
Ultrafiltration
Peritoneal Dialysis
Hypertonic Solutions
Cytokines
Proteins
Albumins
Neutrophils
Molecular Weight
Mesentery
Chemokine CCL2
Extracellular Fluid
Peritoneal Cavity
Glycosaminoglycans
Urea
Wistar Rats
Creatinine

Keywords

  • Dialysate
  • Membrane permeability
  • Mucopolysaccharide
  • Peritoneal dialysis

ASJC Scopus subject areas

  • Nephrology

Cite this

Połubinska, A., Pawlaczyk, K., Kuzlan-Pawlaczyk, M., Wieczorowska-Tobis, K., Chen, C., Moberly, J. B., ... Oreopoulos, D. G. (2000). Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats. Kidney International, 57(3), 1182-1189. https://doi.org/10.1046/j.1523-1755.2000.00946.x

Dialysis solution containing hyaluronan : Effect on peritoneal permeability and inflammation in rats. / Połubinska, Alicja; Pawlaczyk, Krzystof; Kuzlan-Pawlaczyk, Małgorzata; Wieczorowska-Tobis, Katarzyna; Chen, Chi; Moberly, James B.; Martis, L.; Brȩborowicz, Andrzej; Oreopoulos, Dimitrios G.

In: Kidney International, Vol. 57, No. 3, 2000, p. 1182-1189.

Research output: Contribution to journalArticle

Połubinska, A, Pawlaczyk, K, Kuzlan-Pawlaczyk, M, Wieczorowska-Tobis, K, Chen, C, Moberly, JB, Martis, L, Brȩborowicz, A & Oreopoulos, DG 2000, 'Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats', Kidney International, vol. 57, no. 3, pp. 1182-1189. https://doi.org/10.1046/j.1523-1755.2000.00946.x
Połubinska A, Pawlaczyk K, Kuzlan-Pawlaczyk M, Wieczorowska-Tobis K, Chen C, Moberly JB et al. Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats. Kidney International. 2000;57(3):1182-1189. https://doi.org/10.1046/j.1523-1755.2000.00946.x
Połubinska, Alicja ; Pawlaczyk, Krzystof ; Kuzlan-Pawlaczyk, Małgorzata ; Wieczorowska-Tobis, Katarzyna ; Chen, Chi ; Moberly, James B. ; Martis, L. ; Brȩborowicz, Andrzej ; Oreopoulos, Dimitrios G. / Dialysis solution containing hyaluronan : Effect on peritoneal permeability and inflammation in rats. In: Kidney International. 2000 ; Vol. 57, No. 3. pp. 1182-1189.
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abstract = "Background. Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks. Methods. Wistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86{\%}; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment. Results. After four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46{\%} lower for albumin, P <0,001; 33{\%} lower for total protein, P <0.001). The total drained volume after a four hour dwell was 29{\%} higher in the HA group compared with the control (P <0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 ± 6.7 vs. 22.8 ± 9.5{\%}, P <0.01) and lower levels of the cytokines, tumor necrosis factor-α (11.2 ± 14.7 vs. 42.3 ± 35.3 pg/mL, P <0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 ± 86.5 vs. 402.4 ± 258.3 pg/mL. P <0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48{\%}, P <0.01) than tissue from control animals. Conclusions. The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.",
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author = "Alicja Połubinska and Krzystof Pawlaczyk and Małgorzata Kuzlan-Pawlaczyk and Katarzyna Wieczorowska-Tobis and Chi Chen and Moberly, {James B.} and L. Martis and Andrzej Brȩborowicz and Oreopoulos, {Dimitrios G.}",
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TY - JOUR

T1 - Dialysis solution containing hyaluronan

T2 - Effect on peritoneal permeability and inflammation in rats

AU - Połubinska, Alicja

AU - Pawlaczyk, Krzystof

AU - Kuzlan-Pawlaczyk, Małgorzata

AU - Wieczorowska-Tobis, Katarzyna

AU - Chen, Chi

AU - Moberly, James B.

AU - Martis, L.

AU - Brȩborowicz, Andrzej

AU - Oreopoulos, Dimitrios G.

PY - 2000

Y1 - 2000

N2 - Background. Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks. Methods. Wistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment. Results. After four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P <0,001; 33% lower for total protein, P <0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P <0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 ± 6.7 vs. 22.8 ± 9.5%, P <0.01) and lower levels of the cytokines, tumor necrosis factor-α (11.2 ± 14.7 vs. 42.3 ± 35.3 pg/mL, P <0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 ± 86.5 vs. 402.4 ± 258.3 pg/mL. P <0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P <0.01) than tissue from control animals. Conclusions. The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.

AB - Background. Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks. Methods. Wistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment. Results. After four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P <0,001; 33% lower for total protein, P <0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P <0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 ± 6.7 vs. 22.8 ± 9.5%, P <0.01) and lower levels of the cytokines, tumor necrosis factor-α (11.2 ± 14.7 vs. 42.3 ± 35.3 pg/mL, P <0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 ± 86.5 vs. 402.4 ± 258.3 pg/mL. P <0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P <0.01) than tissue from control animals. Conclusions. The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.

KW - Dialysate

KW - Membrane permeability

KW - Mucopolysaccharide

KW - Peritoneal dialysis

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