Dianeal PD4 Research Articles

#2361 The influence of glucose biocompatible solutions to the clinical outcomes of patients treated with continuous ambulatory peritoneal dialysis

Abstract Background and Aims The use of biocompatible glucose solutions is associated with longer preservation of residual renal function and less frequent occurrence of complications in patients on peritoneal dialysis. The aim of this study was to examine the influence of conventional and biocompatible glucose solutions to laboratory parameters and clinical outcomes of PD patients during a four-year period at Zvezdara University Medical Center. Method This retrospective study included 25 incident patients treated with continuous ambulatory peritoneal dialysis (CAPD) during the follow up period from 2018 to 2022. During 2018/2019 these patients used conventional solutions (Dianeal PD4) containing lactate as a buffer, while due to the change in solution production technology in 2020/2021, all patients were transferred to a biocompatible solution (Physioneal 40) with lactate and bicarbonate as a buffer. Clinical outcomes were compared in relation to the administered solution: pain during infusion (measured by a Visual Analogue Scale—VAS), correction of anaemia and bicarbonate, average annual 24h diuresis and 24h ultrafiltration, occurrence of CAPD peritonitis. The statistical significance of the differences between the two periods was checked using the SPSS. Results The average age of 25 patients was 61 ± 14 years, of which 59.1% were male and 40.9% female. The average BMI was 28.5 ± 5.30 kg/m2, and the most common comorbidities were HTA and DM. No statistically significant difference was found for the values of Le, albumin, Hb, PTH, bicarbonate, and K (p ˃ 0.05). During the use of biocompatible solutions, patients had statistically significantly lower Na values (138.84 ± 2.63 vs 137.17 ± 2.41 mmol/l, p = 0.0116, 95% CI 137.15– 138.84) and lower CRP values (15.3 ± 3.3 mg/l vs 7.7 ± 3.2, p = 0.0003, 95% CI 18.60-4.50). Although the dialysis exposure was longer, the rate of peritonitis was lower during the use of biocompatible solutions, but without a statistically significant difference (0.40 episodes per patient-year, vs 0.31 episodes per patient-year, p ˃ 0.05). No statistical significance was found in 24h diuresis value (900 ml vs 750 ml, p = 0.167.95% CI 686.90–1203.31) but the value is expected to be lower due to dialysis duration. Conclusion Our study showed that patients treated with the CAPD method while using a biocompatible solution have statistically significantly higher values of 24h ultrafiltration, lower Na and CRP values and less occurrence of pain during infusion, which significantly affects the quality of life. Although this may indicate better preservation of the peritoneal membrane, a prospective and randomized study is needed to clarify these potential differences.

Standard Clinical Protocol for Bidirectional Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Systemic Leucovorin, 5-Fluorouracil, and Heated Intraperitoneal Oxaliplatin in a Chloride-Containing Carrier Solution.

Intraperitoneal chemotherapy has an established role in the treatment of selected patients with colorectal peritoneal metastases. Oxaliplatin is highly suitable as a chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC), but its use to date has been limited because of the morbidity caused by severe electrolyte and glycemic imbalances associated with 5% glucose as its carrier solution. This report provides an overview of the development, rationale, and application of intraperitoneal chemotherapy and the use of various drugs and carrier solutions. A novel, evidence-based protocol for bidirectional oxaliplatin-based HIPEC in a physiologic carrier solution (Dianeal PD4 dextrose 1.36%) is presented, and its impact on electrolyte and glucose levels is demonstrated. After implementation of the new protocol, the serum electrolyte (sodium, potassium, and chloride) levels, glucose levels, and intravenous insulin requirements were intensively measured in eight consecutive cases immediately before HIPEC (T=0), immediately after HIPEC (T=30), 1h after HIPEC (T=60), and 3h after HIPEC (T=180). The median sodium levels were 140mmol/L at T=0, 138mmol/L at T=30, 140mmol/L at T=60, and 140mmol/L at T=180. The respective median potassium levels were 4.6, 4.2, 3.7, and 3.9mmol/L, and the respective median chloride levels were 112, 111, 111, and 112mmol/L. The respective median glucose levels were 9, 11.5, 10.7, and 8.6mmol/L. The median insulin requirements were respectively 0.5, 1.5, 1.2, and 0 U/h. None of the patients were diabetic. Using a novel protocol for bidirectional oxaliplatin-based HIPEC in Dianeal instead of 5% glucose, the observed fluctuations in this study were minimal and not clinically relevant compared with historical values for electrolyte and glycemic changes using 5% glucose as a HIPEC carrier solution. This novel protocol leads to only minimal and clinically irrelevant electrolyte and glycemic disturbances, and its adoption as the standard protocol for oxaliplatin-based HIPEC should be considered.

Comparative in vitro fungicidal activity of echinocandins against Candida albicans in peritoneal dialysis fluids

The peritoneal dialysis (PD)-associated peritonitis caused by fungi is a relatively rare, but very serious disease. PD fluids (PDFs) affect inhibitory efficacy on the microorganisms' growth, which may compromise the affectivity of some antimicrobials. The purpose of this study was to investigate in vitro the fungicidal effectiveness of echinocandins in diverse PDFs. The fungicidal efficacy of caspofungin (CAS), anidulafungin (ANA), micafungin (MYC) against five clinical isolates of Candida albicans was studied in the different PDFs using time-kill curves. As control substance amphotericin B was used. Echinocandins showed slower and reduced killing of C. albicans in PDFs when compared with the time-kill curves in control bouillon. At concentration of 8 × minimal inhibitory concentration (MIC) the greatest reduction in the growth of C. albicans was seen by ANA in lactate-buffered Nutrineal PD4(®) with 1.1% amino acid (2.33 ± 0.52 log10 CFU ml(-1) ), and by CAS and MYC in lactate-buffered Dianeal PD4(®) with 1.36% glucose (2.36 ± 0.89 log10 CFU ml(-1) and 2.36 ± 0.99 log10 CFU ml(-1) respectively). Using high concentration of 128 × MIC echinocandins achieved fungicidal effect in all PDFs. PDFs may significantly impair the activities of echinocandins, but fungicidal activity of drugs can be achieved at high concentration of 128 × MIC.

Comparative in vitro antimicrobial activity of vancomycin, teicoplanin, daptomycin and ceftobiprole in four different peritoneal dialysis fluids

Peritoneal dialysis used in the treatment of patients with end-stage renal failure is often complicated by peritonitis. Staphylococcus aureus peritonitis is severe, particularly if caused by a methicillin-resistant strain (MRSA). Intraperitoneal administration of drugs for treatment of peritonitis is preferable to intravenous or oral routes because of the resulting higher local antibiotic concentrations. However, peritoneal dialysis fluids (PDFs) have a bacteriostatic effect, which may compromise the efficacy of antibiotics. The bactericidal efficacy of vancomycin, teicoplanin, daptomycin and ceftobiprole was studied in the PDFs Dianeal PD4® (glucose 1.36%), Physioneal 40® (glucose 1.36%), Extraneal® (7.5% icodextrin), and Nutrineal PD4® (1.1% amino acid) using time-kill curves. To simulate in vivo conditions, human serum albumin was added at a final concentration of 2g/l. All four PDFs had a bacteriostatic effect on the growth of the MRSA test isolate. All antibiotics showed less activity in PDFs compared to control broth. Vancomycin and teicoplanin achieved the greatest reduction in bacterial numbers in the amino-acid containing PDF Nutrineal PD4®. Daptomycin showed its highest activity in Extraneal® and better overall efficacy than the other tested antibiotics. Ceftobiprole showed no killing activities in any of the four PDFs. Based on these in vitro data we conclude that the choice of PDFs for intraperitoneal administration is not trivial and could be crucial for therapy outcome.

Calcium and Magnesium Flux in Automated Peritoneal Dialysis

Calcium and magnesium balance in continuous ambulatory peritoneal dialysis (CAPD) has been extensively studied with several of the different formulations of fluid available. Calcium and magnesium balance in automated PD (APD) is less well studied and the effect on Ca and Mg flux is unknown. Data on glucose polymer solutions are also lacking. This prospective observational study was undertaken to examine mass transfer of Ca and Mg in APD patients. 12 patients on APD were studied for two 24-hour periods using, alternately, 1.75 mmol/L and 1.25 mmol/L Ca (Dianeal PD1 and Dianeal PD4; Baxter Healthcare, Newbury, UK) 1.36% glucose-based dialysis fluid for the 9-hour overnight dialysis, followed by a 15-hour daytime dwell of glucose polymer-based fluid (icodextrin). Serum ionized Ca, serum Mg, and dialysate Ca and Mg concentrations were measured at the beginning and end of each period. Mass transfer was calculated as millimoles per exchange. During rapid overnight exchanges with Dianeal PD1 and PD4, mass transfer of Mg and Ca did not show significant correlations with serum levels when using PD1 fluid; however, mass transfer of Mg, but not Ca, was significantly correlated to serum levels when using PD4 fluid. During the long dwell with icodextrin, dialysate drain volume was the most significant factor determining the flux of both Ca and Mg. Mass transfer of Ca and Mg in APD patients using conventional dialysis fluid was not related to drain volume in this study, which differs to studies in CAPD. Flux of Ca and Mg during icodextrin use was found to be dependent on ultrafiltration rate and not dialysate or serum concentration.

Quercetin protects human mesothelial cells against exposure to peritoneal dialysis fluid

During peritoneal dialysis, mesothelial cells have been shown to undergo severe damage due to continuous exposure to peritoneal dialysis fluid (PDF) with cytotoxic physicochemical properties. In this study, we investigated the cytoprotective role of the bioflavonoid Quercetin in the in vitro model of peritoneal dialysis. Immortalized human mesothelial cells (Met5A) were exposed either to regular growth medium or to standard acidic lactate-buffered PDF (Dianeal PD4) or to a more biocompatible lactate-bicarbonate-buffered PDF (Physioneal 40). Parallel cell cultures were supplemented with 200 microM Quercetin. Cytotoxicity was assessed qualitatively by morphologic assessment and quantitatively by the release of cytoplasmic lactate dehydrogenase and fluorescence-activated cell sorting (FACS). PDF exposure with bioincompatible Dianeal PD4 resulted in severe disruption of cell cultures and in significantly increased lactate dehydrogenase (LDH) release (p=0.0007 vs. control). Addition of 200 microM Quercetin significantly decreased the LDH release (p=0.04 vs. "pure" Dianeal PD4 exposure), comparable to control exposure and to more biocompatible Physioneal 40 exposure (p=0.37) and resulted in marked preservation of cell culture monolayers and cellular viability as assessed by FACS. Introduction of cytoprotective agents such as Quercetin may represent an alternate approach to protect mesothelial cells from cytotoxicity of frequently used PDFs, comparably effective to the introduction of novel, more biocompatible, PDFs.

Stability of moxifloxacin injection in peritoneal dialysis solution bags (Dianeal PD1 1·36%®and Dianeal PD1 3·86%®)

Moxifloxacin is a new fluorquinolone with broad-spectrum activity. It is suitable for treating peritonitis in peritoneal dialysis (PD) patients. The objective of this study was to test stability of moxifloxacin in PD solutions stored at different temperatures. Dialysis solution bags were used at two glucose concentrations; Dianeal PD1 1.36% and Dianeal PD1 3.86%. Moxifloxacin solution (2%) was injected into nine 2-L bags of Dianeal PD1 1.36% and nine bags of Dianeal PD1 3.86% under aseptic conditions to achieve a nominal concentration of 25 mg/L. Three bags of Dianeal PD1 1.36% and three bags of Dianeal PD1 3.86% were stored at each of three temperatures (4, 25 and 37 degrees C) and the same way for. Duplicate samples (2 mL) were taken at different times and precipitation, cloudiness, colour and pH was analysed. Moxifloxacin concentrations were measured using a modified HPLC method. The mean moxifloxacin concentration in the Dianeal PD1 1.36% solution remained > or =90% of the initial concentration for 14 days at 4 degrees C, 7 days at 25 degrees C and 3 days at 37 degrees C. For Dianeal PD1 3.86% moxifloxacin concentrations remained > or =90% for 14 days at 4 degrees C, 3 days at 25 degrees C and 12 h at 37 degrees C. Moxifloxacin shows sufficient stability in both PD bags for use in PD patients.

Continuous Flow Peritoneal Dialysis: Assessment of Fluid and Solute Removal in a High-Flow Model of “Fresh Dialysate Single Pass”

♦ Background Growing concern over the limited capacity of the peritoneal dialysis (PD) system has revived interest in continuous flow peritoneal dialysis (CFPD), a modality in which continuous circulation of PD fluid is maintained at a high flow rate using two separate catheters or one dual-lumen catheter. The CFPD regimen contrasts the “inflow/outflow” regimen, which requires specific times devoted to filling and draining the peritoneum via a single-lumen catheter. Historical data established CFPD capabilities in providing higher solute clearance and ultrafiltration rate (UFR) using either an open loop system with a single pass of fresh PD fluid, or various external purifications of the spent dialysate. ♦ Objective To compare, in patients with various peritoneal transport patterns, fluid and solute removal achieved during a standardized program of CFPD versus two control schedules: nightly intermittent peritoneal dialysis (NIPD) and nightly tidal peritoneal dialysis (NTPD). This study focused on small solute clearances and UFR using only isotonic PD solution (Dianeal PD1 1.36%; Baxter Healthcare, Castlebar, Ireland). The model of fresh dialysate, single pass, was used to optimize solute gradients and to characterize the impact of a continuous flow regimen on peritoneal transport characteristics. ♦ Methods In a crossover trial, 4-hour CFPD sessions were performed at a fixed dialysate flow rate (100 mL/minute) in 5 patients being treated with automated PD. A hemofiltration monitor (BM25; Baxter Healthcare, Brussels, Belgium) was adapted to the CFPD technique. The peritoneal cavity was filled through a temporary second catheter and simultaneously drained using the permanent peritoneal access. Fluid and solute removal were compared to data obtained from a control period based on 8-hour sessions of NIPD or NTPD using 13 L of isotonic dialysate. ♦ Results High-flow CFPD enhanced the diffusive transport coefficient compared with the alternative flow regimen in patients ranging from low to high transporters. Weekly creatinine clearance increased from 36.9 L (22.3 – 49.6 L) and 37.3 L (27.5 – 45.0 L) with NIPD and NTPD respectively, to 74.9 L (42.3–107.5 L) with CFPD. Mean UFR was 2.44 mL/min with CFPD versus 0.92 and 0.89 mL/min with NIPD and NTPD respectively. The mass transfer area coefficient (MTAC) of creatinine with CFPD was 2.5-fold that obtained from the peritoneal equilibration test data. ♦ Conclusion Our results confirm that CFPD is highly effective in increasing fluid and solute removal. Furthermore, consistent with historical data, our findings indicate that the enhanced solute transfer is not due only to steeper solute gradients, but also depends on increased MTAC in a wide range of peritoneum transport characteristics.

Effects of Intraperitoneal Hyaluronan on Peritoneal Fluid and Solute Transport in Peritoneal Dialysis Patients

Hyaluronan (HA) is a glycosaminoglycan found in connective tissues and tissue spaces, including the peritoneal cavity. In vivo studies in a rat model of peritoneal dialysis (PD) have shown that addition of HA to PD solution during an intraperitoneal dwell can alter peritoneal fluid transport and protect the peritoneal membrane from the effects of inflammation and repeated infusions of dialysis solution. The current study sought to evaluate the safety of intraperitoneal HA and its effect on peritoneal fluid and solute transport when administered during a dialysis dwell in humans. 13 PD patients were enrolled in a prospective, randomized crossover study involving three dialysis treatments using the following PD solutions: (1) a commercially available PD solution (Dianeal PD-4, 1.36% glucose; Baxter Healthcare Corporation, Alliston, Ontario, Canada); (2) Dianeal PD-4 containing 0.1 g/L HA, and (3) Dianeal PD-4 containing 0.5 g/L HA. Each 6-hour dialysis exchange was separated from the other exchanges by a 2-week washout period. Radioiodinated human serum albumin (RISA) was administered with the dialysis solution to evaluate intraperitoneal volume, net ultrafiltration (UF), and fluid reabsorption. Peritoneal clearances, dialysate/plasma ratios (D/P), and mass transfer area coefficients (MTACs) were determined for sodium, urea, creatinine, albumin, and glucose. Safety was evaluated by monitoring adverse events and changes in serum chemistries. Ten patients completed all three dialysis exchanges and two additional patients completed at least one treatment exchange. There were no reported adverse events related to HA administration and no significant changes in serum chemistries. There were no significant differences in net UF or peritoneal volume profiles among the three treatments. Mean net UF calculated using residual volumes, estimated by RISA dilution, tended to be slightly higher during treatment with solution containing 0.1 g/L HA and 0.5 g/L HA [74 +/- 86 (SE) and 41 +/- 99 mL, respectively] compared to control treatment (-58 +/- 129 mL). Although not statistically significant, there was a trend toward decreased fluid reabsorption during treatment with HA. Solute clearances, D/P ratios, and MTACs were similar for the three treatments. Serum levels of HA were also unaffected by the two treatment solutions. These data support the acute safety of HA when administered intraperitoneally with the dialysis solution to PD patients. Due to the small sample size and variability in net UF and fluid reabsorption, statistically significant differences were not demonstrated for these parameters. However, a trend toward decreased fluid reabsorption was observed, suggesting that HA may act by a mechanism similar to that observed in animal studies. Further studies are necessary to evaluate whether the beneficial effects of HA observed in animal studies can be shown in humans.

Nephrectomy and peritoneal dialysis eliminates circulating renin and controls uraemia in the rat.

The aim of the present study was to develop a rat model for in vivo studies of the local effects of the renin-angiotensin system (RAS) following elimination of circulating renin. Sprague Dawley rats were bilaterally nephrectomised and had a peritoneal dialysis catheter implanted. The rats were maintained on dialysis continuously for 48 hours, using Dianeal PD4 3.86% glucose dialysis solution. The peritoneal catheter and an automated system for dialysate exchange were made in our laboratory. A sham nephrectomised control group of rats was also dialysed. Nephrectomised and sham-operated rats remained active and in good general condition during peritoneal dialysis. At 48 hours, in nephrectomised, dialysed rats, peritoneal urea clearance was 4.14+/-0.52 ml/hour, plasma urea was 40.0+/-7.7 mmol/L, plasma creatinine was 0.423+/- 0.070 mmol/L and plasma renin was below the limit of detection. In conclusion, it was possible to sustain bilaterally-nephrectomised rats on continuous peritoneal dialysis for 48 hours, pending elimination of renin from the circulation. The nephrectomised dialysed rat model should be useful for investigation of the physiological effects of the circulating versus the local RAS.

The Effect of Temperature and Glucose Concentration on the Growth of Microorganisms Commonly Associated with CAPD Peritonitis

Editar: CAPD peritonitis, despite recent advances, re mains a major source of patient morbidity. While many factors contribute to this problem (1,2), the actual growth characteristics of clinically relevant microorganisms might be expected to playa role. To that end, we have studied the in vitra growth characteristics of clinical isolates of Staphylacaccus epidermidis, E. cali, and Pseudamanas aeruginasa in 1.5%, 2.5%, and 4.25% dextrose dialysate fluid. Colonies of the organism were grown on 5% sheep blood agar plates (BAP:BBL, Becton Dickinson Microbiology Systems, Rutherford, NJ) overnight at 35°C. Sufficient quantities of the colonies were suspended in 10 mL normal saline to produce suspensions containing approximately 105 colony-forming units per mL (CFU/mL). The suspensions were inoculated into 200-mL aliquots of the dialysate solutions (Dianeal PD-1, Baxter Healthcare Corporation, Deerfield, IL). The dialysate solutions contained 132 mEq/ L sodium. 3.5 mEq/L calcium, 1.5 mEq/L magnesium, 102 mEq/L chloride and 35 mEq/L of lactate, and 1.5%, 2.5%, or 4.25% dextrose. Each organism and dialysate combination was incubated at 4°C, room temperature (21°C), or 35°C. Twenty microliter volumes at 0, 2, 4, 6, and 24 hours were plated in triplicate onto BAP and incubated at 35°C. The resultant colonies were counted and the mean±SD CFU/mL was determined for each time, temperature, and organism. At 4°C and 21°C regardless of glucose concentration, growth of all organisms appeared to be stagnant with no changes in concentration up to 24 hours. At 35°C, all three organisms exhibited a reduction in colony counts by 24 hours in each dialysate. Figure I represents the observed reduction in colony counts by 24 hours for all organisms and dialysates. Thus changes in medium characteristics (medium osmolalities between 350 mOsm/kg and 510 mOsm/ kg) appear to have little effect on microorganism growth. The ability to recover organisms from inoculated bags for up to 24 hours suggests that early cultures may not be the critical step in microorganism identification. Perhaps the presence of hostproduced inflammatory responses is the factor which significantly alters recovery of organisms in clinical specimens stored outside the body for several hours (3).