Cell Function and Viability in Glucose Polymer Peritoneal Dialysis Fluids

Liberek, Tomasz; Topley, Nicholas; Mistry, Chandra D.; Coles, Gerald A.; Morgan, Tracy; Quirk, Rosalie A.; Williams, Julie

doi:10.1177/089686089301300205

Cited by 58 publications

(30 citation statements)

References 21 publications

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“…This hypothesis is further supported by our observation (27) that M199 at pH 5.5, but not pH 6.5, significantly increased LDH release as compared with M199 at pH 7.4. Witowski et al (21) reported attenuated LDH release in response to lactate-buffered PD solutions with a pH adjusted to 7.4; however, Liberek et al (28) found that, in the presence of 0.1% fetal calf serum, mesothelial cell viability was reduced by both D and E, regardless of pH, when cells were exposed for 3 hours instead of the 1 hour used in the present study. Human monocyte viability was reduced by 7.5% glucose polymer in phosphate-buffered saline (PBS) at pH 7.4 to the same extent as by 1.36% glucose/ lactate solution at pH 5.5 (25).…”

Section: Discussioncontrasting

confidence: 54%

Effects of Conventional and New Peritoneal Dialysis Solutions on Human Peritoneal Mesothelial Cell Viability and Proliferation

Ha¹,

Yu²,

Choi³

et al. 2000

Perit Dial Int

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Objective To investigate the biocompatibility of “new” peritoneal dialysis (PD) solutions with bicarbonate/lactate buffer, non glucose osmotic agents (icodextrin or amino acids), neutral pH, and low levels of glucose degradation products (GDPs). Design Using M199 culture medium as a control, we compared conventional and new PD solutions with respect to their effects on the viability of human peritoneal mesothelial cells (HPMCs) [using lactate dehydrogenase (LDH) release], on DNA damage in HPMCs [using single-cell gel electrophoresis (Comet assay)], and on HPMC proliferation (using [3H]-thymidine incorporation). The experiments were performed after cell growth was synchronized by incubation with serum-free media for 24 hours. The PD solutions tested included commercial 1.5% glucose and 4.25% glucose solutions with 40 mmol/L lactate (D 1.5 and D 4.25, respectively), 7.5% icodextrin (E), 1.1% amino acid (N), 1.5% glucose solution in a triple-chambered bag (Bio 1.5), 1.5% glucose solution in a dual-chambered bag with neutral pH (Bal 1.5), and 1.5% glucose and 4.25% glucose solution containing 25 mmol/L bicarbonate and 15 mmol/L lactate (P 1.5 and P 4.25, respectively). Results When HPMCs were continuously exposed to undiluted PD solutions, D 1.5, D 4.25, P 4.25, and E increased LDH release by more than 60% at 24 hours. All PD solutions tested increased LDH release by more than 75% at 96 hours. With 2-fold diluted PD solutions, only D 4.25 significantly increased LDH release at 96 hours, though not at 24 hours. When cells were exposed to undiluted PD solutions for 60 min and allowed to recover in M199 for up to 96 hours, LDH release was significantly higher at 24 – 96 hours in E (55% – 69%) and D 1.5 (48% –72%) as compared with control [M199 (18%)]. Release of LDH was significantly lower with PD solutions containing lower levels of GDPs than those in D 1.5, suggesting that GDPs may have a role in cell viability. The D solutions (D 1.5 and D 4.25) and E solution also induced significant DNA damage. Both LDH release and DNA damage by D and E were significantly attenuated by adjusting the solution pH to 7.4, suggesting that low pH may be implicated in PD solution–induced DNA damage and cell death. When diluted 2-fold, D 1.5, D 4.25, and P 4.25 decreased [3H]-thymidine incorporation to 43%, 34%, and 41% of control, respectively, at 24 hours and to 45%, 26%, and 35% of control, respectively, at 96 hours. When cells were exposed to undiluted PD solutions for 5 minutes and allowed to recover in M199 for up to 96 hours, D 1.5 and P 4.25—but not D 4.25—significantly inhibited cell proliferation at 24 hours. This effect was sustained up to 96 hours. Conclusions The present in vitro data demonstrate that PD solutions with low pH, or high levels of GDPs, or both, promote HPMC death and DNA damage, and that PD solutions with high osmolality inhibit cell proliferation. Solutions with neutral pH, amino acids, and “low GDPs” appear to be more biocompatible than conventional PD solutions. These results require confirmation in in vivo animal and clinical studies.

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Section: Discussioncontrasting

confidence: 54%

Effects of Conventional and New Peritoneal Dialysis Solutions on Human Peritoneal Mesothelial Cell Viability and Proliferation

Ha¹,

Yu²,

Choi³

et al. 2000

Perit Dial Int

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“…Several in vitro and ex vivo studies have suggested that icodextrin may offer improved peritoneal membrane biocompatibility compared with conventional glucosebased dialysates by virtue of decreased glucose exposure, iso-osmolarity and reduced carbonyl stress. [30][31][32][33][34][35][36][37][38] Shortterm clinical studies involving generally small numbers of patients have demonstrated that dialytic small solute clearances and peritoneal transport characteristics remain well-preserved on icodextrin therapy for up to 24 months of follow up. 5,13,14,20,37,39,40 Moreover, a prospective, open-label, randomized controlled trial of 38 CCPD patients in two centres showed that dialysate effluent concentrations of a variety of peritoneal membrane markers (CA125, interleukin-8, carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type III procollagen) did not differ between glucose-and icodextrin-treated patients over a 2-year period.…”

Section: Biocompatibilitymentioning

confidence: 99%

“…Several in vitro and ex vivo studies have suggested that icodextrin may offer improved peritoneal membrane biocompatibility compared with conventional glucose‐based dialysates by virtue of decreased glucose exposure, iso‐osmolarity and reduced carbonyl stress 30–38 . Short‐term clinical studies involving generally small numbers of patients have demonstrated that dialytic small solute clearances and peritoneal transport characteristics remain well‐preserved on icodextrin therapy for up to 24 months of follow up 5,13,14,20,37,39,40 .…”

Section: Biocompatibilitymentioning

confidence: 99%

Recommendations for the use of icodextrin in peritoneal dialysis patients

Johnson¹,

Agar

Collins

et al. 2003

Nephrology

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SUMMARY:Icodextrin is a starch-derived, high molecular weight glucose polymer, which has been shown to promote sustained ultrafiltration equivalent to that achieved with hypertonic (3.86%/4.25%) glucose exchanges during prolonged intraperitoneal dwells (up to 16 h). Patients with impaired ultrafiltration, particularly in the settings of acute peritonitis, high transporter status and diabetes mellitus, appear to derive the greatest benefit from icodextrin with respect to augmentation of dialytic fluid removal, amelioration of symptomatic fluid retention and possible prolongation of technique survival. Glycaemic control is also improved by substituting icodextrin for hypertonic glucose exchanges in diabetic patients. Preliminary in vitro and ex vivo studies suggest that icodextrin demonstrates greater peritoneal membrane biocompatibility than glucose-based dialysates, but these findings need to be confirmed by long-term clinical studies. This paper reviews the available clinical evidence pertaining to the safety and efficacy of icodextrin and makes recommendations for its use in peritonal dialysis.

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“…The ultrafiltration capacity of a 7.5% icodextrin solution, used for the 8 hour -12-hour overnight dwell in continuous ambulatory peritoneal dialysis (CAPD) patients approximates to that of a 3.86% glucose solution (7). Iso-osmolar icodextrin may be potentially less damaging to the peritoneum and to peritoneal defense compared to the hyperosmolar (346 -486 mOsm/kg) glucose solutions currently used (8)(9)(10).…”

Section: ♦ ♦ ♦ ♦ ♦ Conclusionmentioning

confidence: 99%

Assessment of the Effectiveness, Safety, and Biocompatibility of Icodextrin in Automated Peritoneal Dialysis

Posthuma¹,

Pieter

Donker

et al. 2000

Perit Dial Int

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Objective Our study assessed the efficacy, safety, and biocompatibility of icodextrin (I) solution compared to glucose (G) solution as the daytime dwell in continuous cycling peritoneal dialysis (CCPD). Design In a randomized, open, prospective, parallel group study of two years’ duration, either I or G was used for the long daytime dwell in CCPD patients. Method The study was carried out in a university hospital and teaching hospital. Established CCPD patients and patients new to the modality were both included. Clinic visits were made at three-month intervals. In all patients, clinical data were gathered; ultrafiltration (UF) was recorded; and serum, urine, and dialysate samples and effluents were collected. Peritoneal defense characteristics and mesothelial markers were determined. Every six months, peritoneal kinetics studies were performed, and serum samples for icodextrin metabolites were taken. Results Thirty-eight patients (19 G, 19 I) started the study. The median follow-up was 16 months and 17 months respectively (range: 0.5 – 26 months and 3 – 26 months, respectively). Daytime UF volumes increased significantly (p < 0.001), and 24-hour UF tended to increase from baseline in the I group. Dialysate creatinine clearance increased non significantly in both groups over time. In I patients, serum disaccharides (maltose) concentration increased from 0.05 ± 0.01 mg/mL [mean ± standard error of mean (SEM)] at baseline, to an average concentration in the follow-up visits of 1.15 ± 0.04 mg/mL (p < 0.001). At the same time, serum sodium levels decreased from 138.1 ± 0.7 mmol/L to an average concentration in the follow-up visits of 135.9 ± 0.8 mmol/L (p < 0.05). At 12 months, the serum sodium concentration increased to a non significant difference from baseline. Serum osmolality increased, but did not differ significantly from G users at any visit. During peritonitis (P), daytime dwell UF decreased significantly compared to non peritonitis (NP) episodes in G patients (p < 0.001), but remained stable in I patients. Total 24-hour UF also decreased in G patients (p < 0.001), but not in I patients. In these I patients, serum disaccharides increased from 0.05 ± 0.01 mg/mL to 1.26 ± 0.2 mg/mL during follow-up. During peritonitis, serum disaccharides concentration did not increase further (1.47 ± 0.2 mg/mL, p = 0.56). Thirty P episodes occurred during follow-up: 16 in G patients and 14 in I patients (1 per 17.6 months and 1 per 21.9 months, respectively). After one year, absolute number and percentage of effluent peritoneal macrophages (PMΦs) were significantly higher in I patients than in G patients. The difference in percentage persisted after two years. The phagocytic capacity of PMΦs decreased over time, resulting in a borderline significant difference for coagulase-negative staphylococci phagocytosis (p = 0.05) and a significant difference for E. coli phagocytosis (p < 0.05) in favor of I patients. PMΦ oxidative metabolism, PMΦ cytokine production, and effluent opsonic capacity remained stable over time with no difference between the groups. Mass transfer area coefficients (MTACs) and clearances were stable and appeared unaffected by G or I treatment. Effluent cancer antigen 125 (CA125) was stable in G users and tended to decrease in I users. Effluent interleukin-8 (IL-8), carboxy-terminal propeptide of type I procollagen (PICP), and amino-terminal propeptide of type III procollagen (PIIINP) did not change over time and did not differ between the groups. Conclusions The use of I for the long daytime dwell in CCPD led to an increase in total UF of at least 261 mL per day, which was maintained over at least 24 months. During I treatment, serum I metabolites increased significantly and serum sodium concentrations decreased initially. As a result, serum osmolality increased slightly. Clinical adverse effects did not accompany these findings. The UF gain in the I patients was even higher during P, without a further increase in serum I metabolites. CCPD patients using I did equally well as G-treated patients with regard to clinical infections and most peritoneal defense characteristics. However, in a few peritoneal defense tests, I-treated patients did better. Peritoneal transport variables did not change over time. Peritoneal membrane markers did not change throughout the study and did not differ between the groups.

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Cell Function and Viability in Glucose Polymer Peritoneal Dialysis Fluids

Cited by 58 publications

References 21 publications

Effects of Conventional and New Peritoneal Dialysis Solutions on Human Peritoneal Mesothelial Cell Viability and Proliferation

Effects of Conventional and New Peritoneal Dialysis Solutions on Human Peritoneal Mesothelial Cell Viability and Proliferation

Recommendations for the use of icodextrin in peritoneal dialysis patients

Assessment of the Effectiveness, Safety, and Biocompatibility of Icodextrin in Automated Peritoneal Dialysis

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