Hyperbranched Polyglycerol is an Efficacious and Biocompatible Novel Osmotic Agent in a Rodent Model of Peritoneal Dialysis

Mendelson, Asher A.; Guan, Qiunong; Chafeeva, Irina; Roza, Gerald A. Da; Kizhakkedathu, Jayachandran N.; Du, Caigan

doi:10.3747/pdi.2012.00148

Cited by 35 publications

(39 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, as a percentage, the "equi-osmotic" efficiency concentration of HPG (0.33 mmol/g, and σ = 0.22) compared with 1.36% G (5.6 mmol/g, and σ = 0.05) would be approximately 5% ( Table 1). The concentration of HPG that is osmotically equivalent to 2.27% G can be calculated to be approximately 8% (Table 1), which is more or less exactly what was found when 30 mL of a 7.5% HPG solution was assessed with respect to UF properties during a 4-hour dwell in a rodent model of PD (18). Actually, an 8% HPG solution should be slightly more efficient than 2.27% G in producing UF because, compared with G, HPG has lower diffusivity and less reabsorption to the plasma compartment.…”

Section: Rippementioning

confidence: 73%

Article Commentary: Hyperbranched Polyglycerol: A Future Alternative to Polyglucose in Peritoneal Dialysis Fluids?

Rippe

2013

Perit Dial Int

View full text Add to dashboard Cite

Section: Rippementioning

confidence: 73%

Article Commentary: Hyperbranched Polyglycerol: A Future Alternative to Polyglucose in Peritoneal Dialysis Fluids?

Rippe

2013

Perit Dial Int

View full text Add to dashboard Cite

“…Our previous studies have demonstrated the efficacy of small HPG molecules (0.5–3 kDa) as potential osmotic agents in fluid removal and their biocompatibility with the peritoneum in a rat model of acute (4 h) PD [18, 19]. The present study has compared the long-term effects of HPG (1 kDa) with glucose on overall health status and its local influence on the peritoneum using a rat model of chronic PD, and has demonstrated that as compared to electrolyte solution, HPG did not induce any change in the blood chemistry, but IP injection of PYS significantly changed the levels of Cre, ALP, ALB and Glob (including ALB/Glob ratio) during 3 months of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…HPG (1 kDa) was synthesized by anionic ring opening multi-branching polymerization, and its characteristics were verified as described previously [18, 19]. …”

Section: Methodsmentioning

confidence: 99%

“…Recent reports in literature demonstrate the biocompatibility and potential use of this macromolecule in many different biomedical applications, such as a human serum albumin substitute [14], a drug carrier [15, 16] and a colloid for cold preservation of cells or organs [17]. Our preliminary studies have shown that HPG (0.5–3 kDa)-based PD solutions can be prepared by varying the HPG concentration from 2.5 to 15% (w/v) within an osmolality range (294–424 mOsm/kg) and neutral pH (6.6–7.4) that are comparable to Dianeal (2.5% glucose, 395 mOsm/L, pH 5.2) and PYS (2.27% glucose, 395 mOsm/L, pH 7.4) [18, 19], and by a single dwell time these HPG-based PD solutions produced similar or significantly better fluid and waste removal while causing less damage to peritoneal membrane (PM) in rats compared to either Dianeal (2.5% glucose) or PYS (2.27% glucose) [18, 19]. The objective of the current study was to investigate the long-term effects of HPG-based PD solution (denoted here as HPG) compared to conventional glucose-based PYS in rats, especially on the PM structure and function.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hyperbranched polyglycerol is superior to glucose for long-term preservation of peritoneal membrane in a rat model of chronic peritoneal dialysis

Mendelson

Guan

et al. 2016

J Transl Med

Self Cite

View full text Add to dashboard Cite

BackgroundReplacing glucose with a better biocompatible osmotic agent in peritoneal dialysis (PD) solutions is needed in PD clinic. We previously demonstrated the potential of hyperbranched polyglycerol (HPG) as a replacement for glucose. This study further investigated the long-term effects of chronic exposure to HPG as compared to a glucose-based conventional PD solution on peritoneal membrane (PM) structure and function in rats.MethodsAdult male Wistar rats received once-daily intraperitoneal injection of 10 mL of HPG solution (1 kDa, HPG 6%) compared to Physioneal™ 40 (PYS, glucose 2.27%) or electrolyte solution (Control) for 3 months. The overall health conditions were determined by blood chemistry analysis. The PM function was determined by ultrafiltration, and its injury by histological and transcriptome-based pathway analyses.ResultsHere, we showed that there was no difference in the blood chemistry between rats receiving the HPG and the Control, while PYS increased serum alkaline phosphatase, globulin and creatinine and decreased serum albumin. Unlike PYS, HPG did not significantly attenuate PM function, which was associated with smaller change in both the structure and the angiogenesis of the PM and less cells expressing vascular endothelial growth factor, α-smooth muscle actin and MAC387 (macrophage marker). The pathway analysis revealed that there were more inflammatory signaling pathways functioning in the PM of PYS group than those of HPG or Control, which included the signaling for cytokine production in both macrophages and T cells, interleukin (IL)-6, IL-10, Toll-like receptors, triggering receptor expressed on myeloid cells 1 and high mobility group box 1.ConclusionsThe results from this experimental study indicate the superiority of HPG to glucose in the preservation of the peritoneum function and structure during the long-term PD treatment, suggesting the potential of HPG as a novel osmotic agent for PD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1098-z) contains supplementary material, which is available to authorized users.

show abstract

“…Theoretically, the molecular properties of HPG make it more efficient than glucose in producing ultrafiltration. Promising studies [15, 16] in rodents showed better preservation of UF and fewer toxic effects on the peritoneal membrane. However, studies in humans have not yet been conducted, and there are several questions remaining such as the ramifications of accumulation of HPG over time, or whether HPG molecules are metabolized in plasma and in the peritoneal cavity.…”

Section: Hyperbranched Polyglycerolmentioning

confidence: 99%

Visions in a Crystal Ball: The Future of Peritoneal Dialysis

Bargman¹,

Girsberger²

2018

Blood Purif

View full text Add to dashboard Cite

Background: Peritoneal dialysis (PD) is one of the corner stones of renal replacement therapy and should be strongly considered if preemptive kidney transplantation is not available. Summary: There are several initiatives that may help the growth in the use of PD around the world. First, PD is an underused and valuable option in patients with heart failure and the chronic cardiorenal syndrome, especially in those with frequent hospitalizations despite optimal medical therapy. To identify these patients, an interdisciplinary approach of nephrologists and cardiologists is needed. These patients and other CKD patients with significant residual kidney function may do well with a regimen employing fewer than the usual number of bag exchanges, referred to as “incremental” dialysis. Second, acute kidney injury (AKI) is a worldwide burden with high morbidity and mortality, especially in low income countries. To reach the goal of zero preventable deaths caused by AKI by 2025 endorsed by the International Society of Nephrology, PD is the therapy of choice for treatment in this setting. Third, although dextrose has served well as the osmotic agent in PD solutions, there has been a continuous search for alternative agents. Hyperbranched polyglycerol might be such an osmole. Finally, to obviate the need for production and delivery of bags of PD solution, the development of home-generated dialysate is of interest. Key Message: The future of PD lies not only in accruing experience from the past decades, but also in staying open to other uses.

show abstract

Hyperbranched Polyglycerol is an Efficacious and Biocompatible Novel Osmotic Agent in a Rodent Model of Peritoneal Dialysis

Abstract: ORIGINAL ARTICLES♦

Cited by 35 publications

References 53 publications

Article Commentary: Hyperbranched Polyglycerol: A Future Alternative to Polyglucose in Peritoneal Dialysis Fluids?

Article Commentary: Hyperbranched Polyglycerol: A Future Alternative to Polyglucose in Peritoneal Dialysis Fluids?

Hyperbranched polyglycerol is superior to glucose for long-term preservation of peritoneal membrane in a rat model of chronic peritoneal dialysis

Visions in a Crystal Ball: The Future of Peritoneal Dialysis

Contact Info

Product

Resources

About