Glucose-based Solutions Research Articles

Peritoneal dialysis-related peritonitis due to Pasteurella multocida in Australia.

Domestic animals are common in Australian households; however, there is little research into the potential risks these animals pose to patients undergoing in-home peritoneal dialysis (PD). Cats and dogs are known to carry many potential pathogens, including Pasteurella multocida. We reviewed the ANZDATA Peritoneal Dialysis Peritonitis Registry for cases of peritonitis due to Pasteurella multocida between 2011 and 2023. Cases identified were younger and more likely to be female compared with the Australian PD population who developed peritonitis due to other organisms. Of the total 32 episodes, 75% were using automated PD with glucose-based solutions. Two cases requiring removal of the PD catheter and transfer to haemodialysis and no deaths were reported. Whilst outcomes were largely favourable, it is likely that many of these cases could have been prevented. Education for people undergoing PD should include information about the potential infectious hazards of domestic animals.

Glucose-Free Solutions Mediated Inhibition of Oxidative Stress and Oxidative Stress-Related Damages in Peritoneal Dialysis: A Promising Solution.

Oxidative stress (OxSt) and inflammation are common in end-stage renal disease and dialysis patients; they are known risk factors for cardiovascular disease and mortality. In peritoneal dialysis (PD), OxSt and inflammation are even further increased compared to the already increased oxidative stress of their pre-dialysis phase. This is due to the high glucose-based solutions currently used, whose continuous contact with the peritoneal membrane can induce significant long-term morphological and functional changes (mesothelial to mesenchymal transition, thickening, neo-angiogenesis and fibrosis) of the peritoneal membrane. Oxidative stress plays a very important role in these processes, which may compromise the peritoneal dialysis procedure. There is, therefore, the need for more biocompatible dialysis fluids with polymers other than glucose to prevent and treat OxSt and inflammation. The most known and used of such glucose-free and more biocompatible peritoneal dialysis solutions is icodextrin, which has shown a protective effect from oxidative stress. This has supported the consideration of the use of glucose-free-based peritoneal dialysis fluids in order to reduce oxidative stress and improve peritoneal membrane survival. Studies investigating peritoneal dialysis with the use of osmo-metabolic agents (L-carnitine, xylitol and their combination) in peritoneal fluids replacing glucose-based fluids are, in fact, ongoing. They represent a promising strategy to reduce OxSt, preserve the peritoneal membrane's integrity and improve patients' outcome.

Can one long peritoneal dwell with icodextrin replace two short dwells with glucose?

Due to the slower dissipation of the osmotic gradient, icodextrin-based solutions, compared to glucose-based solutions, can improve water removal. We investigated scenarios where one icodextrin-based long dwell (Extraneal) replaced two glucose-based exchanges. The three-pore model with icodextrin hydrolysis was used for numerical simulations of a single exchange to investigate the impact of different peritoneal dialysis schedules on fluid and solute removal in patients with different peritoneal solute transfer rates (PSTRs). We evaluated water removal (ultrafiltration, UF), absorbed mass of glucose (AbsGluc) and carbohydrates (AbsCHO, for glucose and glucose polymers), ultrafiltration efficiency (UFE = UF/AbsCHO) per exchange, and specified dwell time, and removed solute mass for sodium (ReNa), urea (ReU), and creatinine (ReCr) for a single peritoneal exchange with 7.5% icodextrin (Extraneal®) and glucose-based solutions (1.36% and 2.27%) and various dwell durations in patients with fast and average PSTRs. Introducing 7.5% icodextrin for the long dwell to replace one of three or four glucose-based exchanges per day leads to increased fluid and solute removal and higher UF efficiency for studied transport groups. Replacing two glucose-based exchanges with one icodextrin exchange provides higher or similar water removal and higher daily sodium removal but slightly lower daily removal of urea and creatinine, irrespective of the transport type present in the case of reference prescription with three and four daily exchanges. One 7.5% icodextrin can replace two glucose solutions. Unlike glucose-based solutions, it resulted only in minor differences between PSTR groups in terms of water and solute removal with UFE remaining stable up to 16h.

Oxidative stress reduction by icodextrin-based glucose-free solutions in peritoneal dialysis: Support for new promising approaches.

Oxidative stress (OxSt) and inflammation are common in CKD and are known CV and mortality risk factors. In peritoneal dialysis (PD) OxSt and Inflammation even increase due to the use of glucose-based solutions. This study analyzed in 15 PD patients the effect of 3 and 6 months of treatment with icodextrin-based glucose-free solutions on OxSt and inflammation, evaluating p22phox protein expression (Western blot), NADPH oxidase subunit, essential for OxSt activation, MYPT-1 phosphorylation state, marker of RhoA/Rho kinase pathway (ROCK) activity, involved in the induction of OxSt (Western blot) and Malondialdehyde (MDA) production (fluorimetric assay). Interleukin (IL)-6 blood level (chemiluminescence assay) has been measured and used as a marker of inflammation. p22phox protein expression, MYPT 1 phosphorylation, and MDA were reduced after 3 months from the start of icodextrin (1.28 ± 0.18 d.u. vs. 1.50 ± 0.19, p = 0.049; 0.89 ± 0.03 vs. 0.98 ± 0.03, p = 0.004; 4.20 ± 0.18 nmol/mL vs. 4.84 ± 0.32 nmol/mL, p = 0.045, respectively). In a subgroup of 9 patients who continued the treatment up to 6 months, MYPT-1 phosphorylation was further reduced at 6 months compared to baseline (0.84 ± 0.06 vs. 0.99 ± 0.04, p = 0.043), while p22phox protein expression was reduced only at 6 months versus baseline (1.03 ± 0.05 vs. 1.68 ± 0.22, p = 0.021). In this subgroup, MDA was reduced at 6 months versus baseline (4.03 ± 0.24 nmol/mL vs. 4.68 ± 0,32, p = 0.024) and also versus 3 months (4.03 ± 0.24 vs. 4.35 ± 0.21, p = 0.008). IL-6 level although reduced both at 3 and 6 months, did not reach statistical significance. The reduction of OxSt with icodextrin-based PD solutions, although obtained in a small patients cohort and in a limited time duration study, strongly supports the rationale of using osmo-metabolic agents-based fluids replacing glucose-based fluids. Ongoing studies with these agents will provide information regarding preservation of peritoneal membrane integrity, residual renal function, and reduction of CVD risk factors such as OxSt and inflammation.

#2881 Glucose free-based solutions reduce oxidative stress in peritoneal dialysis: support for a new promising approach

Abstract Background and Aims Oxidative stress (OxSt) and inflammation are common in CKD which are known CV and mortality risk factors. In peritoneal dialysis (PD) OxSt and Inflammation even increase due to the use of glucose-based solutions. This study evaluated in PD patients the effect of 3 and 6 months treatment with icodextrin-based glucose-free solutions on OxSt and inflammation. Method In 15 PD patients using a molecular biology approach, p22phox protein expression (Western blot), subunit of NADPH oxidase, essential for OxSt activation, MYPT-1 phosphorylation state, marker of RhoA/Rho kinase pathway activity, deeply involved in OxSt generation (Western blot) and Malondialdehyde (MDA) production (fluorimetric assay), marker of lipid peroxidation, have been evaluated. High-sensitive C Reactive Protein (hsCRP) (immunoturbidimetric assay) and interleukin (IL)-6 (chemiluminescence assay), have been used as marker of inflammation. Results p22phox protein expression, MYPT-1 phosphorylation, and MDA level were reduced after 3 months from the start of icodextrin based solutions (1.28 ± 0.18 d.u. vs 1.50 ± 0.19, p = 0.049; 0.89 ± 0.03 vs 0.98 ± 0.03, p = 0.004; 4.20 ± 0.18 nmol/mL vs 4.84 ± 0.32 nmol/mL, p = 0.045, respectively). In a subgroup of 9 patients who continued the treatment up to 6 months MYPT-1 phosphorylation was further reduced at 6 months compared to baseline (0.84 ± 0.06 vs 0.99 ± 0.04, p = 0.043), while p22phox protein expression was reduced only at 6 months from baseline (1.03 ± 0.05 vs 1.68 ± 0.22, p = 0.021). In this subgroup MDA blood level was reduced at 6 months from baseline (4.03 ± 0.24 nmol/mL vs 4.68 ± 0.32, p = 0.024) and was also significantly reduced vs 3 months (4.03 ± 0.24 vs 4.35 ± 0.21, p = 0.008). IL-6 level, although reduced compared to baseline, did not reach statistical significance both at 3 and 6 months, while hsPCR was unchanged. Conclusion The icodextrin-based PD solutions mediated reduction of OxSt related proteins and inflammation we have provided, although obtained in a small cohort of patients and for a limited time duration, strongly support the rationale of using in PD osmo-metabolic agents-based solutions replacing the currently used glucose-based fluids. The results of ongoing studies with these agents in PD patients will provide definitive proofs to better preserve peritoneal membrane integrity and residual renal function but also to reduce CV risk factors such as OxSt and inflammation.

Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge.

Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

Análise da degradação foliar de Lisianthus (Eustoma grandiflorum) na pós-colheita por espectroscopia de reflectância VIS-NIR-SWIR

ABSTRACT: It is known that floriculture is very important for the world economic scenario. Nevertheless, the vase life of cut flowers is determined by a short time span. This study evaluated the spectral behavior during leaf degradation of lisianthus (Eustoma grandiflorum) flower stems in the postharvest, in different preservative solutions, and estimating its leaf pigments by hyperspectral data. Lisianthus floral stems were subjected to preservative solutions with different concentrations of sucrose, glucose, phytohormones and deionized water. Leaves from these stems were collected every 4 days for further hyperspectral analysis. Spectra was determined in laboratory with a sensor collecting at the range of 350-2500 nm. In order to analyze the use of the spectra to detect the performance of the preservative solutions, statistical tests were used at each wavelength. Pigment prediction was assessed by the CAR/CLF ratio (Ratio between Carotenoids and Chlorophyll) from the spectral curves, using PLSR and RRMSE. The glucose-based solutions registered positive effects on the preservation of floral stems, especially at the dose of 180 g/L. The solutions based on sucrose and phytohormones registered similarities in the spectral curves among the doses, demonstrating equality in leaf preservation. The discriminant analyses demonstrated there was statistical difference in the spectral responses in the doses for each solution used. The CAR/CLF ratio had reasonable coefficients of 0.6 and RRMSE below 6.99%. The hyperspectral analyses presented a potential for the evaluation of leaf degradation in lisianthus floral stems in different pulsing solutions used in the postharvest.

Comparison of different freezing techniques, extenders, and cryoprotectants on quality and fertility of cryopreserved Salmo trutta f. fario sperm

There is still a lack of standardized methodology in the cryopreservation of Salmo trutta f. fario sperm. Thus, the present study was designed to compare current freezing protocols to improve and as well as to examine the post-thaw quality and fertilizing ability of cryopreserved sperm in Salmo trutta f. fario. Sperm samples were diluted at a 1:10 ratio in one of three extenders (Alsever’s solution, glucose-based, and ionic-based) containing four types of cryoprotectant (DMSO, DMA, MeOH, glycerol) at 10% concentration and frozen in 0.1 mL pellets on surface of the dry ice (solid carbon dioxide, 79°C) or in 0.25 mL straws 2 cm above of the liquid nitrogen (LN2) surface at a rate of ~30°C for 10 min.1 before storage in a mL cryotank (-196°C). The frozen sperm cells in straws and pellets were thawed in a water bath at 25°C for 30 s and at 20°C for 6 s respectively. Fertilization was carried out using a ratio of 5x105 sperm/egg in both freezing methods. The glucose-based solution including glycerol produced the highest post-thaw progressive motility (62.5 ± 1.24%), motility duration (57.2 ± 0.46 s), and viability (56.4 ± 1.57%) (p < 005) in the straw method. In breeding trials, similarly, sperm frozen-thawed with the glucose-based solution including glycerol produced the highest fertilization (54.2 ± 0.36%) and hatching (30.6 ± 0.28%) in the straw method. Fresh sperm used as control produced 82.6 ± 0.45% and 78.4 ± 1.27% fertilization and hatching respectively. It was concluded that sperm frozen in straws produced higher post-thaw sperm motility and fertility of eggs than those frozen in pellets. Also, the results suggest using of glycerol-supplemented glucose solution because of producing better results in both freezing techniques.

The genetic variant SLC2A1 -rs1105297 is associated with the differential analgesic response to a glucose-based treatment in newborns.

Neonatal pain is a critical issue in clinical practice. The oral administration of glucose-based solutions is currently one of the most common and effective nonpharmacologic strategies for neonatal pain relief in daily minor procedures. However, a varying degree of analgesic efficacy has been reported for this treatment. Environmental, maternal, and genetic factors may explain this variability and potentially allow for a personalized analgesic approach, maximizing therapeutic efficacy and preventing side effects. We investigated the exposome (ie, the set of clinical and anthropometric variables potentially affecting the response to the therapy) and the genetic variability of the noradrenaline transporter gene (solute carrier family 6 member 2 [ SLC6A2 ]) and 2 glucose transporter genes (solute carrier family 2 member 1 [ SLC2A1 ] and 2 [ SLC2A2 ]) in relation to the neonatal analgesic efficacy of a 33% glucose solution. The study population consisted in a homogeneous sample of more than 1400 healthy term newborns. No association for the exposome was observed, whereas a statistically significant association between the G allele of SLC2A1 -rs1105297 and a fourfold decreased probability of responding to the therapy was identified after multiple-testing correction (odds ratio of 3.98, 95% confidence interval 1.95-9.17; P = 4.05 × 10 -4 ). This allele decreases the expression of SLC2A1-AS1 , causing the upregulation of SLC2A1 in the dorsal striatum, which has been suggested to be involved in reward-related processes through the binding of opioids to the striatal mu-opioid receptors. Altogether, these results suggest the involvement of SLC2A1 in the analgesic process and highlight the importance of host genetics for defining personalized analgesic treatments.

A randomized clinical trial to evaluate the effects of icodextrin on left ventricular mass index in peritoneal dialysis

Left ventricular hypertrophy is a risk factor for cardiovascular mortality in patients on peritoneal dialysis (PD). Because icodextrin has a greater ultrafiltration power compared with glucose-based solutions for long dwell, it could improve left ventricular mass by reducing fluid overload. This was a randomized clinical trial that included patients on PD recruited from 2 teaching hospitals, in Sao Paulo—Brazil. Patients were allocated to the control glucose group (GLU) or the intervention icodextrin (ICO) group. Clinical and cardiac magnetic resonance image (MRI) parameters were evaluated at baseline and 6 months after randomization. The primary outcome was the change in left ventricular mass adjusted by surface area (ΔLVMI), measured by cardiac MRI. A total of 22 patients completed the study (GLU, N = 12 and ICO, N = 10). Baseline characteristics such as age, sex, underlying disease, and time on dialysis were similar in both groups. At baseline, 17 patients (77.3%) presented with left ventricular hypertrophy with no difference between groups (p = 0.748). According to the total body water (TBW)/extracellular water (ECW) ratio, 36.8% and 80% of patients from GLU and ICO groups, respectively, were considered hypervolemic (p = 0.044). During follow-up, ΔLVMI was 3.9 g/m (− 10.7, 2.2) in GLU and 5.2 (− 26.8, 16.8) in ICO group (p = 0.651). ΔLVMI correlated with change in brain natriuretic peptide (r = 0.566, p = 0.044), which remained significant in a multiple regression analysis. The use of the icodextrin-based solution in prevalent patients on PD compared with a glucose-based solution was not able to improve LMV. A larger randomized trial with a longer follow-up period may be needed to show changes in LVM in this patient population.Trial registration: this study has been registered at ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification #RBR-2mzhmj2, available at: https://ensaiosclinicos.gov.br/pesquisador.

Peritoneal Expression of SGLT-2, GLUT1, and GLUT3 in Peritoneal Dialysis Patients

Introduction: In peritoneal dialysis (PD) patients, the peritoneal membrane is affected by glucose-based solutions used as peritoneal dialysate fluids. This exposure leads to changes of the membrane which may eventually culminate in fibrosis and method failure. In vitro or animal studies demonstrated that glucose transporters are upregulated upon exposure to these solutions. Expression studies of glucose transporters in human peritoneum have not been reported yet. Methods: Expression of SGLT-2, GLUT1, and GLUT3 in human peritoneal biopsies was analyzed by real-time polymerase chain reaction and Western blot analysis. The localization of these glucose transporters in the peritoneum was evaluated by immunohistochemistry using a Histo-Score. Results: Peritoneal biopsies of patients (healthy controls, uremic, PD, and encapsulating peritoneal sclerosis [EPS]) were analyzed. We found evidence of SGLT-2, GLUT1, and GLUT3 expression in the peritoneal membrane. Protein expression of SGLT-2 increases with PD duration and is significantly enhanced in EPS patients. All transporters were predominantly, but not exclusively, located adjacent to the vessel walls of the peritoneal membrane. Conclusion: Our study showed that SGLT-2, GLUT1, and GLUT3 were regularly expressed in the human peritoneum. SGLT-2 was particularly upregulated in PD patients with EPS, suggesting that this upregulation may be associated with pathological changes in the peritoneal membrane in this syndrome. Since preclinical studies in mice show that SGLT-2 inhibitors or downregulation of SGLT-2 ameliorated pathological changes in the peritoneum, SGLT-2 inhibitors may be potentially promising agents for therapy in PD patients that could reduce glucose absorption and delay functional deterioration of the peritoneal membrane in the long term.

Biological Effects of XyloCore, a Glucose Sparing PD Solution, on Mesothelial Cells: Focus on Mesothelial-Mesenchymal Transition, Inflammation and Angiogenesis.

Glucose-based solutions remain the most used osmotic agents in peritoneal dialysis (PD), but unavoidably they contribute to the loss of peritoneal filtration capacity. Here, we evaluated at a molecular level the effects of XyloCore, a new PD solution with a low glucose content, in mesothelial and endothelial cells. Cell viability, integrity of mesothelial and endothelial cell membrane, activation of mesothelial and endothelial to mesenchymal transition programs, inflammation, and angiogenesis were evaluated by several techniques. Results showed that XyloCore preserves mesothelial and endothelial cell viability and membrane integrity. Moreover XyloCore, unlike glucose-based solutions, does not exert pro-fibrotic, -inflammatory, and -angiogenic effects. Overall, the in vitro evidence suggests that XyloCore could represent a potential biocompatible solution promising better outcomes in clinical practice.

MO717EFFECT ON BLOOD PRESSURE OF UNCOMPENSATED 130 MM SODIUM DIALYSATE IN CAPD PATIENT WITH RESISTANT HYPERTENSION

Abstract Background and Aims In peritoneal dialysis (PD) blood pressure (BP) control is largely unsatisfied mainly due to sodium retention. Currently, sodium removal in PD patients depends substantially on ultrafiltration. Lowering sodium in PD solution might improve sodium removal by diffusion, though the real benefit of low PD solution remains still undetermined. Method In this case report, we used a novel uncompensated glucose-based PD solution (DextroCore LS, Iperboreal Pharma, Italy) containing 130 mM sodium to treat resistant hypertension in 78-year-old female treated by CAPD (3 dwells glucose 1.5% a day, Na 132). Results At baseline, Ambulatory BP monitoring (ABPM) showed 24h-BP (152/81 mmHg), diurnal BP (151/83 mmHg) and nocturnal BP (153/75 mmHg), with inversion of circadian rhythm in systolic BP (systolic night/day ratio: 1.02), despite the use of three anti-hypertensive (doxazosin 4mg, amlodipine 10 mg, telmisartan 80 mg) and diuretic (furosemide 250 mg) at adequate doses. She had no signs of hypervolemia. We switched from standard PD (132 mM/L) to low sodium PD solution using 1.5% glucose bags with sodium concentration of 130 mM. CAPD schedule was confirmed. Second ABPM after six months reported a reduction 24h BP (131/73 mmHg), diurnal (134/75 mmHg) and nocturnal BP (122/67 mmHg), with restoring of circadian BP rhythm. No change in body weight, UF and residual diuresis was found. Diet and therapy prescriptions were unmodified. No side effects were reported. Conclusion Six-months PD treatment with uncompensated glucose-based PD solution containing 130 mM sodium in all daily dwells has allowed to reduce systolic BP (-16 mmHg) in a CAPD patient affected by resistant hypertension, with no change in ultrafiltration and residual diuresis.

MO900ENHANCED EXPRESSION OF THIOREDOXIN-INTERACTING PROTEIN (TXNIP) RESULTS IN REDUCED TRX ACTIVITY AND INCREASED OXIDATIVE DNA-DAMAGE IN PERITONEAL DIALYSIS PATIENTS*

Abstract Background and Aims Peritoneal dialysis (PD) is an effective method of renal replacement therapy (RRT). The long-term use of PD as a RRT is limited due to adverse effects of high glucose-based PD solutions to the structure and function of the peritoneal membrane. PD patients show excessive oxidative stress compared to healthy controls. However, there are only scare information on pathophysiological mechanisms leading to oxidative DNA-damage in PD patients. Therefore, the aim of this study was to elucidate the mechanism leading to excessive oxidative stress in human samples of the peritoneal membrane. Method Human peritoneal biopsies of healthy controls, PD patients and patients with EPS were collected. Protein expression of TXNIP was analysed by ELISA using plasma samples and by immunohistochemistry of peritoneal biopsies using a Histo-Score. Protein expression of TRX was examined by immunohistochemistry. To measure TRX activity a kit based on the reduction of insulin by reduced TRX was used. The resulting oxidative DNA-damage was investigated by immunohistochemistry using a Histo-Score or by ELISA using plasma samples of patients. Results Biopsies from the peritoneum of 8 healthy controls, 11 uremic patients, 22 patients on PD < 12 months or 29 patients on PD > 12 months and of 13 patients with EPS were collected. The age of the uremic patients was higher (median 65.0 years, IQR: 49.0-75.0) than in the other subgroups (PD < 12 months: median 62.0 years, IQR: 52.25-68.25, PD > 12 months: median 60.0 years, IQR: 39.5-70.5 and EPS: median 51.00 years, IQR: 40.0-57.5). In general, there were more female participants in the control-group (75 %) compared to all other groups (uremic group: 27%, PD < 12 months: 18 %, PD >12 months: 41% and EPS group 33 %). Time on PD was longer in EPS patients (median 72.0 months) than in PD patients (PD <12 months: median 10.0 months and PD > 12 months: 39.0 months). The ELISA study of plasma samples showed that TXNIP is upregulated in all groups compared to healthy controls. Immunohistochemically studies of peritoneal biopsies showed also an upregulation of TXNIP upon exposure to high glucose-based dialysis fluids (PD and EPS group). Interestingly, a glucose-related change in protein expression of its interacting partner and cellular anti-oxidant TRX was only observed in EPS samples. TRX activity in uremic patients was almost unchanged compared to healthy controls except for one patient. However, enhanced TXNIP expression correlated with a reduced activity of TRX in samples of PD as well as EPS patients. Reduced TRX activity resulted in an increase of produced ROS. Therefore, the effect on the generation of oxidative damage was analysed by ELISA of plasma samples and by immunohistochemistry on peritoneal sections. Both analysis showed an increase in the oxidative DNA-damage marker 8-Hydroxydesoxyguanosin (8-OHdG) in all PD samples and samples of EPS patients compared to the control group. Conclusion Here, we show that high glucose-based peritoneal dialysis solutions lead to an upregulation of TXNIP expression in human peritoneal samples. This increase in TXNIP expression reduces the activity of its interacting partner an antioxidant TRX leading to an increase in ROS production and enhanced levels of DNA-damage. In this study, we elucidate for the first time a novel mechanism showing that glucose-dependent upregulation of TXNIP induces a perturbation of the intracellular redox equilibrium leading to alterations of the peritoneal membrane. Therefore, manipulation of TXNIP expression may be a promising therapeutic target to improve peritoneal membrane function.

POS-629 PERITONEAL MEMBRANE HISTOPATHOLOGIC CHANGES CAUSED BY PERITONITIS IN CONTINUOUS AMBULATORY PERITONEAL DIALYSIS PATIENTS: TWO CASE REPORTS

Long-term Peritoneal Dialysis (PD) causes morphologic and functional changes in the peritoneal membrane (PM) which is defined as peritoneal fibrosis, a known cause of loss of peritoneal ultrafiltration capacity. Inflammation, angiogenesis , and bioincompatible of peritoneal dialysis solution are a key event during the pathogenesis. Peritonitis remains a major problem in Peritoneal Dialysis. Excessive peritoneal inflammatory responses lead to mesothelial cell exfoliation and thickening of the submesothelial, resulting in peritoneal fibrosis and sclerosis. We report two cases of the patient in Continuous Ambulatory Peritoneal Dialysis (CAPD), focus on PM histopathologic changes. Case 1. A male, 47 years old, suffered from repeated peritonitis. After fourth episode of infection, the catheter was malfunction and removed. He was done on CAPD for 7 years with glucose base solution. Histopathologically, peritoneal membrane showed diffuse fibrosis and hyalinization, without mesothelial cell lining nor inflammatory cell infiltrate. He was transferred to hemodialysis. Case 2. A 28 years old male, came with chief complaint of fever, abdominal pain, and cloudy effluent in CAPD fluid. On third episode of peritonitis, Empirical treatment with cefotaxime intraperitoneal was done , however CAPD catheter was malfunctioned and removed. He was done on CAPD for 6 years with glucose base solution. The peritoneal membrane histopathology showed diffuse fibrosis and hyalinization, involving vessels, foci of lymphoplasmacytic cells infiltration, without mesothelial cell. He was transferred to hemodialysis. The success of PD was dependent on the structural and functional integrity of the PM. The mesothelium lines the PM and is the first line of defense against chemical / bacterial insult. Peritonitis remains a major complication of PD and cause of ultrafiltration/technique failure, morbidity and mortality. The mortality risk of PD-related peritonitis was 16-18%. Bioincompatible PD solution is also associated with production of proinflammatory and profibrotic cytokines. High peritoneal glucose exposure is associated with increased incidence of relapsing/recurrent peritonitis and conduct proinflammatory and profibrotic reactions in the peritoneal cavity leading to fibrosis and malfunction after 6-7 years. Peritoneal fibrosis was detected in 50% and 80% of PD patients within one and two years on PD. Pathological alterations in the vasculature of peritoneal include hyalinization of the blood vessels, vasculopathy, and submesothelial thickening.Figure 2Case 2.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Peritonitis episode altered peritoneal structure and functional. Neglected infection and repeated infection led to PD catheter removal. Glucose based solution may a contributing factor for membrane failure due to inflammation and fibrosis after 6-7 years.

How do glucose-based oral rehydration salt solutions with osmolarity ≤ 270 mOsm/L compare with ≥ 310 mOsm/L solutions for treating adolescents and adults with cholera?

How do glucose-based oral rehydration salt solutions with osmolarity ≤ 270 mOsm/L compare with ≥ 310 mOsm/L solutions for treating adolescents and adults with cholera?

P1133XYLITOL-BASED PERITONEAL DIALYSIS SOLUTIONS MITIGATED IN VITRO MESOTHELIAL AND ENDOTHELIAL TO MESENCHYMAL TRANSITION

Abstract Background and Aims Fibrosis, angiogenesis and microvascular alteration are main pathogenetic mechanisms involved in the progressive loss of the peritoneal ultrafiltration capacity in patients undergoing peritoneal dialysis (PD). Main cause of this condition is the continuous peritoneal exposure to hyperosmotic and hyperglycaemic agents. High glucose level activates the Mesothelial to Mesenchymal Transition (MMT) and the Endothelial-to-Mesenchymal (EndMT) program, which are responsible for the development of fibrosis/chronic peritoneal damage. Moreover, the high glucose content of PD solution may induce the VEGF production with consequent neo-angiogenesis. Therefore, the introduction of more biocompatible solutions in clinical practice is necessary for preserving the long-term peritoneal membrane. To this purpose we tested the in vitro effects of a new commercially available PD solutions containing xylitol, carnitine and reduced glucose, at comparable osmotic strength (XyloCore). Method Human vein microvascular endothelial cells (HMVEC) were cultured in EGM™-2MV medium (Lonza) and Human peritoneal mesothelial cell line (HMrSV5) were cultured in Dulbecco's Modified Eagle Medium (DMEM; Gibco) containing 10% fetal bovine serum. Cells were cultured to confluence and then treated for 3 hours with serum free medium, XyloCore 0.7 (0.5% Glucose, 0.7% Xylitol and 0.02% L-carnitine), XyloCore 1.5 (0.5% Glucose, 1.5% Xylitol and 0.02% L-carnitine) and commercially available glucose-based solutions (Fixioneal) 1.36% and 2.27% Glucose. Gene expression of MMT/EndMT, apoptosis, inflammation, extracellular remodeling and angiogenesis markers was evaluated by real-time PCR. Cell viability was assayed by MTS assay. Results Our in vitro results demonstrated that XyloCore solutions, by influencing only partially the mesothelial and endothelial cells viability, demonstrated a good biocompatible profile. Then, gene expression analysis of HMVEC and HMrSV5 treated with XyloCore solutions revealed a significant down-regulation of transcripts encoding for MMT and EndMT biomarkers (Zinc finger protein SNAI1, TGF-beta, alpha-SMA and vimentin), and pivotal biological elements involved in apoptosis (Bcl-2), extracellular matrix remodeling (matrix metallopeptidases), inflammation (IL-1beta, IL-6) and angiogenesis (Vascular endothelial growth factor) compared to glucose-based solutions with comparable osmotic strength. Conclusion These in vitro results demonstrated, for the first time, that XyloCore solutions have a better biocompatible impact and less pro-fibrotic potentials compared to conventional glucose-based solutions. These effects, if confirmed in in vivo studies, could have interesting clinical potentials.

P1146ENHANCED EXPRESSION OF THIOREDOXIN-INTERACTING-PROTEIN (TXNIP) MAY REGULATE OXIDATIVE DAMAGE IN PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Glucose-based solutions used as peritoneal dialysis fluids influence the peritoneal membrane. Exposure to high glucose-based peritoneal dialysis solutions induces reactive oxygen species (ROS) production due to upregulation of TXNIP as shown by several studies in rats as well as in human primary cells. Enhanced expression of TXINP also regulates oxidative damage. Therefore the aim of this study was to investigate the expression of TXNIP and the extent of oxidative damage in human peritoneal biopsies. Method Human peritoneal biopsies of healthy controls, PD patients and patients with EPS were collected. TXNIP and thioredoxin-1 (TRX) mRNA expression was determined by qPCR. Protein expression and the extent of oxidative damage were examined by immunohistochemistry. Results Biopsies from the peritoneum of 7 healthy controls, 36 patients on PD without signs of EPS as well as of 12 patients with EPS were collected. The age of the healthy controls was higher (median 64.00 years, IQR: 53.00-70.00) than in the other subgroups (PD: median 60.50 years, IQR: 46.00-69.00 and EPS: median 51.00 years, IQR: 38.00-58.75). Furthermore, compared to the PD- (39 %) and EPS-group (33 %), there were more female participants in the control-group (86 %). Time on PD was longer in EPS patients (median 70.00 months) than in PD patients (median 33.50 months). In a preliminary study, exposure to high glucose-based peritoneal dialysis solutions did not markedly influence the mRNA expression of TXNIP and TRX. However, on protein level a significant glucose-related upregulation of TXNIP could be observed especially in PD patients. Interestingly, there was no glucose-related change in protein expression of its interacting partner and cellular anti-oxidant TRX. To study the effect of TXNIP expression on the generation of oxidative damage, pH2AX positive nuclei were counted on peritoneal membrane sections. A slight increase of pH2AX positive nuclei upon exposure to dialysis solutions could be observed in the cohort analysed. Conclusion Here, we show for the first time a clear tendency for upregulation TXNIP in human peritoneal tissue after exposure to high glucose-based peritoneal dialysis solutions especially in PD patients. This increase in TXNIP expression may correlate with the accumulation of oxidative damage of macromolecules. Therefore, manipulation of TXNIP expression may be a promising therapeutic target to improve peritoneal membrane function.

P1155REMOVAL OF PHOSPHATE AND CREATININE DURING PD WITH DIFFERENT GLUCOSE CONCENTRATIONS

Abstract Background and Aims Adequate removal of creatinine and phosphate is one of the key objectives in peritoneal dialysis (PD). Whereas the mechanism of creatinine removal is well known, there are gaps in understanding regulation of phosphate removal. Clinical studies show that although the size of both molecules is similar, their removal might behave differently (Badve et al CJASN 2008). Several, but not all, studies have suggested that peritoneal phosphate clearance is larger when using CAPD than APD prescriptions, suggesting the dwell time or duration is an important determinant of phosphate clearance. The aim of the study was to investigate specifically the effect of dwell duration at the level of single PD exchange with different glucose concentrations on peritoneal phosphate clearance. Method A prolonged 8-hour PET was carried out in 32 clinically stable PD patients with each of three glucose-based solutions: 1.36% (G1), 2.27% (G2), and 3.86% (G3) with temporary drainage at 1 and 4 hours of peritoneal dwell. Dialysate and blood samples were taken to measure infused and drained volume and concentration of phosphate and creatinine in dialysate and blood. Clearances were calculated for a single exchange for each solution and for 4-hour (4H) and 8-hour (8H) dwell periods. For each patient, the 4-hour creatinine D/P ratio for G3 was calculated. The clearance ratio, ClR, defined as the ratio of solute clearance for particular solution to its clearance for the G1 solution, was calculated for both solutes and each solution and dwell durations. Results The obtained values of 4H creatinine D/P ratio for G3 solution were 0.67±0.11 (mean±SD). The values of solute clearances per single exchange expressed in mL/min, are presented in table below. Creatinine and phosphate clearances were found to be solution and dwell duration dependent with p<0.001. The clearances of both solutes were correlated for the same dwell duration or solution (not for creatinine G2 for 4H vs 8H) with p<0.05. Moreover, solute clearances were also correlated with creatinine D/P for 4H but not for 8H. The clearances of phosphate were also correlated with that for creatinine each solution at both dwell durations with p<0.001. Both calculated ClR were found to be dependent on the solution (p<0.001) but not dwell duration. Similar dependence on solution and correlations are valid in one analyze solute mass removal. Conclusion Phosphate and creatinine clearances were found to be well correlated during a long, 8-hour PET proving similarities in their transport. Interestingly, the dependence of both clearances and ClR on solution glucose concentration suggest that the removal of phosphate as well as creatinine depends on the ultrafiltration induced by glucose concentration in dialysis solution.

Long Peritoneal Dialysis Dwells With Icodextrin: Kinetics of Transperitoneal Fluid and Polyglucose Transport.

Background and objective: During peritoneal dialysis (PD), the period of effective net peritoneal ultrafiltration during long dwells can be extended by using the colloidal osmotic agent icodextrin but there are few detailed studies on ultrafiltration with icodextrin solution exceeding 12 h. We analyzed kinetics of peritoneal ultrafiltration in relation to icodextrin and its metabolites for 16-h dwells with icodextrin.Design, setting, participants, and measurements: In 20 clinically stable patients (mean age 54 years; 8 women; mean preceding time on PD 26 months), intraperitoneal dialysate volume (VD) was estimated from dilution of 125I-human serum albumin during 16-h dwell studies with icodextrin 7.5% solution. Sodium was measured in dialysate and plasma. In 11 patients, fractional absorption of icodextrin from dialysate, dialysate, and plasma amylase and high and low (Mw <2 kDa) Mw icodextrin fractions were analyzed.Results: Average VD increased linearly with no difference between transport types. At 16 h, the cumulative net ultrafiltration was 729 ± 337 ml (range −18 to 1,360 ml) and negative in only one patient. Average transcapillary ultrafiltration rate was 1.40 ± 0.36 ml/min, and peritoneal fluid absorption rate was 0.68 ± 0.38 ml/min. During 16 h, 41% of the initial mass of icodextrin was absorbed. Plasma sodium decreased from 138.7 ± 2.4 to 136.5 ± 3.0 mmol/L (p < 0.05). Dialysate glucose G2–G7 oligomers increased due to increase of G2–G4 metabolites while G6–G7 metabolites and higher Mw icodextrin fractions decreased. In plasma maltose and maltotriose (G2–G3 metabolites) increased while higher Mw icodextrin oligomers were almost undetectable. Dialysate amylase increased while plasma amylase decreased.Conclusions: Icodextrin resulted in linear increase of VD with sustained net UF lasting 16 h and with no significant difference between peritoneal transport types. In plasma, sodium and amylase declined, G2–G3 increased whereas larger icodextrin fractions were not detectable. In dialysate, icodextrin mass declined due to decrease of high Mw icodextrin fractions while low Mw metabolites, especially G2–G3, increased. The ability of icodextrin to provide sustained UF during very long dwells – which is usually not possible with glucose-based solutions – is especially important in anuric patients and in patients with fast peritoneal transport.