Mass Transfer Area Coefficient Research Articles

#3022 Rationale and design of the CORDIAL first-in-human clinical trial: a system for sorbent-assisted continuous flow peritoneal dialysis

Abstract Background and Aims Peritoneal dialysis has important disadvantages, including low plasma clearance and a limited technique survival. A new device for sorbent-assisted continuous flow peritoneal dialysis has been designed (Wearable Artificial KIDney, WEAKID) that is based on continuous recirculation (rapid cycling) of peritoneal dialysate via a single-lumen peritoneal catheter with regeneration of dialysate using sorbents. Anticipated benefits are a better plasma clearance a higher mass transfer area coefficient with continuous flow of dialysate and enhanced diffusion due to a higher time-averaged plasma-dialysate concentration gradient with sorbent-based dialysate regeneration, and a prolonged technique survival thanks to lower peritonitis risk (less (dis)connections) and a lower glucose exposure. Method This is a first-in-human, prospective, open-label, non-randomized, single-arm, multicenter study, that will be performed at the University Medical Center Utrecht (Utrecht, The Netherlands), Università degli studi di Modena e Reggio Emilia (Italy), and Instituto de Investigación Hospital Universitario La Paz, Servicio Madrileño de Salud (Spain). We aim to include 12 stable, adult PD patients. In the first week, blood, urine, and dialysate samples will be collected over three separate days to assess the efficacy of the patient's standard PD schedule. The WEAKID system will then be tested in a clinical setting on 6 days over a period of 2 weeks (three consecutive days per week). During the first week, participants will be treated with WEAKID without sorbents for 4h (first day) or 8h (second and third day). The second week, treatment will consist of WEAKID with sorbents for 4h (first day) or 8h (second and third day). This way, exposure to new components of the system is incremental and the effectiveness of continuous recirculation of dialysate and that the added effect of sorbent-based dialysate regeneration can be analyzed separately. Outcomes The primary aim of this first-in-human clinical trial is to evaluate the (short term) clinical safety and performance of WEAKID treatment in a clinical setting. The primary safety objective will be assessed by describing and examining the incidence of: Key secondary objectives include an evaluation of efficacy in terms of plasma clearance, ultrafiltration, net base release, and patient tolerance. Planning Inclusion of the first patient is expected in January 2024, the final inclusion is expected to take place in November 2024.

Model-Informed Precision Dosing of Vancomycin in Adult Patients Undergoing Hemodialysis.

Model-informed precision dosing (MIPD) maximizes the probability of successful dosing in patients undergoing hemodialysis. In these patients, area under the concentration-time curve (AUC)-guided dosing is recommended for vancomycin. However, this model is yet to be developed. The purpose of this study was to address this issue. The overall mass transfer-area coefficient (KoA) was used for the estimation of vancomycin hemodialysis clearance. A population pharmacokinetic (popPK) model was developed, resulting in a fixed-effect parameter for nonhemodialysis clearance of 0.316 liters/h. This popPK model was externally evaluated, with a resulting mean absolute error of 13.4% and mean prediction error of -0.17%. KoA-predicted hemodialysis clearance was prospectively evaluated for vancomycin (n = 10) and meropenem (n = 10), with a correlation equation being obtained (slope of 1.099, intercept of 1.642; r = 0.927, P < 0.001). An experimental evaluation using an in vitro hemodialysis circuit validated the developed model of KoA-predicted hemodialysis clearance using vancomycin, meropenem, vitamin B6, and inulin in 12 hemodialysis settings. This popPK model indicated a maximum a priori dosing for vancomycin-a loading dose of 30 mg/kg, which achieves the target AUC for 24 h after first dose with a probability of 93.0%, ensured by a predialysis concentration of >15 μg/mL. Maintenance doses of 12 mg/kg after every hemodialysis session could achieve the required exposure, with a probability of 80.6%. In conclusion, this study demonstrated that KoA-predicted hemodialysis clearance may lead to an upgrade from conventional dosing to MIPD for vancomycin in patients undergoing hemodialysis.

正常腎機能患者のプレガバリン中毒に対する血液浄化療法の効果(Effects of blood purification therapy for pregabalin intoxication in patients with normal kidney function)

要旨 プレガバリンを過量服薬した正常腎機能患者に対してextracorporeal treatment（ECTR）を施行し，経過中の血中プレガバリン濃度を液体クロマトグラフィー質量分析法（LC–MS）で測定した2例を経験したため報告する。症例1は49歳の女性。プレガバリン5,750mg，ベニジピン160mgなどを過量服用し救急搬送された。来院時，舌根沈下あり気管挿管した。洞停止が頻回にみられ，循環不全進行のためノルアドレナリン，ドブタミンを開始した。来院後11時間より血液濾過透析（hemodiafiltration: HDF）を開始し5時間施行した。プレガバリンの半減期はHDF前22.8時間，HDF中2.3時間であった。症例2は41歳の女性。プレガバリン3,225mg，アムロジピン65mgなどを過量服薬し救急搬送された。ICU入室後に意識レベルが低下したため，気管挿管した。来院後5時間より血液透析（hemodialysis: HD）を開始し4時間施行した。HD終了後に意識レベルの改善がみられた。正常腎機能患者のプレガバリン中毒に対してECTRを導入したところ，血中プレガバリン濃度は速やかに低下し早期の意識レベル改善，循環動態改善の効果が得られた。昏睡状態や呼吸不全，循環不全を合併する重症プレガバリン中毒に対しては，正常腎機能であっても早期の状態改善にECTRが有効である可能性が示唆された。

A Uremic Pig Model for Peritoneal Dialysis.

With increasing interest in home dialysis, there is a need for a translational uremic large animal model to evaluate technical innovations in peritoneal dialysis (PD). To this end, we developed a porcine model with kidney failure. Stable chronic kidney injury was induced by bilateral subtotal renal artery embolization. Before applying PD, temporary aggravation of uremia was induced by administration of gentamicin (10 mg/kg i.v. twice daily for 7 days), to obtain uremic solute levels within the range of those of dialysis patients. Peritoneal transport was assessed using a standard peritoneal permeability assessment (SPA). After embolization, urea and creatinine concentrations transiently increased from 1.6 ± 0.3 to 7.5 ± 1.2 mM and from 103 ± 14 to 338 ± 67 µM, respectively, followed by stabilization within 1–2 weeks to 2.5 ± 1.1 mM and 174 ± 28 µM, respectively. Gentamicin induced temporary acute-on-chronic kidney injury with peak urea and creatinine concentrations of 16.7 ± 5.3 mM and 932 ± 470 µM respectively. PD was successfully applied, although frequently complicated by peritonitis. SPA showed a low transport status (D/P creatinine at 4 h of 0.41 (0.36–0.53)) with a mass transfer area coefficient of 9.6 ± 3.1, 4.6 ± 2.6, 3.4 ± 2.3 mL/min for urea, creatinine, and phosphate respectively. In conclusion, this porcine model with on-demand aggravation of uremia is suitable for PD albeit with peritoneal transport characterized by a low transport status.

Peritoneal Protein Clearance Is Associated With Cardiovascular Events but Not Mortality in Peritoneal Dialysis Patients.

IntroductionAssociation of peritoneal protein clearance (Pcl) with outcomes in patients with peritoneal dialysis (PD) is uncertain. Thus, we aimed to investigate its impact on cardiovascular events and all-cause mortality in patients with PD and factors associated with Pcl.MethodsPrevalent patients with PD from January 2014 to April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters and Angiopoietin-2-Tie2 system cytokines. Mass transfer area coefficient of creatinine (MTACcr) and Pcl were calculated. Patients were dichotomized into two groups by the median Pcl level (68.5 ml/day) and were followed up prospectively until the end of the study (1 October 2018).ResultsA total of 318 patients with PD [51.2% men, mean age 56.7 ± 14.3 y, median PD duration 31.5 (12.1–57.2) months] were enrolled. Among them, 25.7% were comorbid with diabetes and 28.6% had a history of cardiovascular disease (CVD). After being followed up for up to 43.9 (24.2–50.3) months, 63 had developed cardiovascular events, and 81 patients were died. Among them, the high Pcl group had occurred 39 cardiovascular events and 51 deaths, and the low Pcl group had 24 cardiovascular events and 30 deaths. Kaplan-Meier analysis showed that both the occurrence of cardiovascular events and all-cause mortality were increased in patients with high Pcl. However, after adjusting for important confounders and serum Angiopoietin-2 (Angpt-2) level, Pcl was still an independent risk factor for cardiovascular events [hazard ratio (HR) = 1.006 (1.000–1.012), p = 0.038] but not mortality. On multivariate regression analysis, serum albumin, MTACcr, and body mass index (BMI) were found to be independently associated with Pcl.ConclusionHigh Pcl is an independent risk factor for cardiovascular events but not all-cause mortality. The prediction of cardiovascular events by Pcl was independent of serum Angpt-2.

Modeling acid-base transport in hemodialyzers

One important objective of the hemodialysis treatment is the neutralization of interdialytic acid generation by transport of bicarbonate and other buffer bases from dialysis fluid to the patient via the hemodialyzer. Quantification of solute transport in hemodialyzers, in general, employs the concept of dialysance, a parameter that is often constant for given flow conditions, smaller than both the blood and dialysate flow rates, and independent of the solute concentration difference between blood and dialysate. This approach has been applied to bicarbonate transport in hemodialyzers, but such an approach neglects the transport of dissolved carbon dioxide (CO2) between dialysate and plasma, chemical equilibrium between bicarbonate and CO2, and other acid-base chemical reactions within blood. We describe a novel, one-dimensional model of bicarbonate and CO2 transport in hemodialyzers. The model equations were solved numerically and fitted to published data to estimate mass transfer-area coefficients for the relevant chemical species. Base excess in blood was assumed constant in the hemodialyzer. Simulations were performed for a dialysate bicarbonate concentration of 32 mEq/L at constant blood and dialysate flow rates and different plasma bicarbonate concentrations at the inlet of the hemodialyzer, both with and without CO2 transport. In the latter case, the bicarbonate mass transfer-area coefficient was adjusted to achieve the same total carbon dioxide transport. Calculated dialysance for CO2 exceeded the blood flow rate due to its conversion from bicarbonate in the hemodialyzer, and all calculated dialysances varied with inlet plasma bicarbonate concentration. We concluded that acid-base transport in hemodialyzers cannot be universally characterized by dialysances that are always less than the blood flow rate and independent of the concentration difference between dialysate and blood.

Influence of dialysate temperature on creatinine peritoneal clearance in peritoneal dialysis patients: a randomized trial

BackgroundPatients on continuous ambulatory peritoneal dialysis (PD) are encouraged to warm dialysate to 37 °C before peritoneal infusion; main international PD guidelines do not provide specific recommendation, and patients generally warm dialysate batches partially or do not warm them at all. Warming of dialysate is a time-consuming procedure, not free from potential risks (i.e. degradation of glucose), and should be justified by a clear clinical benefit.MethodsWe designed a single blind randomized controlled trial where 18 stable PD patients were randomized to receive a peritoneal equilibration test either with dialysate at a controlled temperature of 37 °C (intervention group) or with dialysate warmed with conventional methods (control group). Primary end-point was a higher peritoneal creatinine clearance in patients in the intervention group.ResultsPatients in the intervention group did not show a significantly higher peritoneal creatinine clearance when compared to the control group (6.38 ± 0.52 ml/min vs 5.65 ± 0.37 ml/min, p = 0.2682). Similar results were obtained for urea peritoneal clearance, mass transfer area coefficient of creatinine and urea. There were no significant differences in total abdominal discomfort questionnaire score, blood pressure and body temperature between the two groups.ConclusionsUsing peritoneal dialysate at different temperatures without causing significant side effects to patients appears feasible. We report a lack of benefit of warming peritoneal dialysate to 37 °C on peritoneal clearances; future PD guidelines should not reinforce this recommendation.Trial registrationNCT04302649, ClinicalTrials.gov; date of registration 10/3/2020 (retrospectively registered).

Comparison of Longitudinal Membrane Function in Peritoneal Dialysis Patients According to Dialysis Fluid Biocompatibility

IntroductionPreservation of peritoneal function is essential in long-term peritoneal dialysis. Biocompatible dialysis solutions might prevent or postpone the membrane alteration resulting in ultrafiltration failure and consecutive morbidity and mortality.MethodsWe conducted an observational cohort study in which we made a longitudinal comparison between the course of peritoneal solute and fluid transport during treatment with conventional and biocompatible solutions. Therefore, prospectively collected peritoneal transport data from the yearly standard peritoneal permeability analysis were analyzed in 251 incident patients treated between 1994 and censoring in 2016. Fluid transport included small pore and free water transport. Solute transport was assessed by creatinine mass transfer area coefficient and glucose absorption. Linear mixed models including change point analyses were performed. Interaction with peritonitis was examined.ResultsOne hundred thirty-five patients received conventional and 116 biocompatible solutions. Sixty-seven percent (conventional) and 64% (biocompatible) of these underwent minimally three transport measurements. Initially, biocompatible fluids showed higher small solute transport and lower ultrafiltration than conventional fluids up to 3 years. Thereafter, conventional fluids showed an increase in small solute transport (+2.7 ml/min per year; 95% confidence interval [CI]: 0.9 to 4.5) and a decrease of free water transport (−28.0 ml/min per year; 95% CI: −60.4 to 4.4). These were minor or absent in biocompatible treatment. Peritonitis induced a decrease of transcapillary ultrafiltration after 2 years on dialysis with conventional solutions (−291 ml/min per year; 95% CI: −550 to −32) while this was absent in biocompatible treatment.ConclusionDespite a higher initial solute transport with biocompatible solutions, these have less influence on functional long-term peritoneal alterations than conventional solutions.

In vitro efficacy and safety of a system for sorbent-assisted peritoneal dialysis.

A system for sorbent-assisted peritoneal dialysis (SAPD) was designed to continuously recirculate dialysate via a tidal mode using a single lumen peritoneal catheter with regeneration of spent dialysate by means of sorbent technology. We hypothesize that SAPD treatment will maintain a high plasma-to-dialysate concentration gradient and increase the mass transfer area coefficient of solutes. Thereby, the SAPD system may enhance clearance while reducing the number of exchanges. Application is envisaged at night as a bedside device (12 kg, nighttime system). A wearable system (2.0 kg, daytime system) may further enhance clearance during the day. Urea, creatinine, and phosphate removal were studied with the daytime and nighttime system (n = 3 per system) by recirculating 2 liters of spent peritoneal dialysate via a tidal mode (mean flow rate: 50 and 100 mL/min, respectively) for 8 h in vitro. Time-averaged plasma clearance over 24 h was modeled assuming one 2 liter exchange/day, an increase in mass transfer area coefficient, and 0.9 liters ultrafiltration/day. Urea, creatinine, and phosphate removal was 33.2 ± 4.1, 5.3 ± 0.5, and 6.2 ± 1.8 mmol, respectively, with the daytime system and 204 ± 28, 10.3 ± 2.4, and 11.4 ± 2.1 mmol, respectively, with the nighttime system. Time-averaged plasma clearances of urea, creatinine and phosphate were 9.6 ± 1.1, 9.6 ± 1.7, and 7.0 ± 0.9 mL/min, respectively, with the nighttime system and 10.8 ± 1.1, 13.4 ± 1.8, and 9.7 ± 1.6 mL/min, respectively, with the daytime and nighttime system. SAPD treatment may improve removal of uremic toxins compared with conventional peritoneal dialysis, provided that peritoneal mass transport will increase.

P1120QUANTIFICATION OF ACID-BASE TRANSPORT IN HEMODIALYZERS

Abstract Background and Aims Quantification of bicarbonate and dissolved carbon dioxide (CO2) transport in hemodialyzers can be described by the product of a dialysance (D) and their respective concentration differences between dialysate and plasma. It is typically assumed that D values are constant for a given hemodialyzer and flow conditions; however, this approach neglects the chemical interconversion of bicarbonate and dissolved CO2 within blood. We assessed the validity of this approach by developing a comprehensive mathematical model of acid-base transport in hemodialyzers. Method Mass balance relationships in a hemodialyzer were defined using a one-dimensional model with counter-current flows of blood and dialysate. The molecular biochemistry of bicarbonate, dissolved CO2, and non-bicarbonate buffer in both plasma and erythrocytes, together with carbaminohemoglobins within erythrocytes, was assumed to be in equilibrium as described by Rees and Andreassen (Crit Rev Biomed Eng 2005). The model equations were solved numerically, and optimal mass transfer-area coefficients for bicarbonate and dissolved CO2 were determined by comparing model predictions with the data from Sombolos et al (Artif Organs 2005). The latter data included measured concentrations of bicarbonate and dissolved CO2 in plasma and dialysate inlet and outlet flows at a blood flow rate of 300 mL/min, dialysate flow rate of 700 mL/min, and dialysate bicarbonate concentration of 32.5 mEq/L. Base excess of blood was assumed as -5 mEq/L. Model simulations then evaluated the effect of the plasma bicarbonate concentration at the blood inlet (assuming constant mass transfer-area coefficients and flow rates) on D for both bicarbonate (Dbic) and dissolved CO2 (DCO2). D values were calculated as the loss of the molecule from the dialysate divided by the difference in inlet concentrations of dialysate and plasma. Results Optimal mass transfer-area coefficients for bicarbonate and dissolved CO2 were 396 and 1360 mL/min, respectively. Simulation results at different plasma bicarbonate concentrations at the blood inlet ([Bicarbonate]) as expected during a typical hemodialysis treatment are tabulated: Conclusion Quantification of acid-base transport in hemodialyzers requires dialysance values for bicarbonate and dissolved CO2 that are not constant but instead are dependent on the plasma bicarbonate concentration at the blood inlet for a given hemodialyzer at fixed blood and dialysate flow rates.

Longitudinal Changes of NF-\u03baB Downstream Mediators and Peritoneal Transport Characteristics in Incident Peritoneal Dialysis Patients

The role of intra-peritoneal mediators in the regulation peritoneal transport is not completely understood. We investigate the relation between longitudinal changes in dialysis effluent level of nuclear factor kappa-B (NF-κB) downstream mediators and the change in peritoneal transport over 1 year. We studied 46 incident PD patients. Their peritoneal transport characteristics were determined after starting PD and then one year later. Concomitant dialysis effluent levels of interleukin-6 (IL-6), cyclo-oxygenase-2 (COX-2) and hepatocyte growth factor (HGF) are determined. There were significant correlations between baseline and one-year dialysis effluent IL-6 and COX-2 levels with the corresponding dialysate-to-plasma creatinine level at 4 hours (D/P4) and mass transfer area coefficient of creatinine (MTAC). After one year, patients who had peritonitis had higher dialysis effluent IL-6 (26.6 ± 17.4 vs 15.1 ± 12.3 pg/ml, p = 0.037) and COX-2 levels (4.97 ± 6.25 vs 1.60 ± 1.53 ng/ml, p = 0.007) than those without peritonitis, and the number of peritonitis episode significantly correlated with the IL-6 and COX-2 levels after one year. In contrast, dialysis effluent HGF level did not correlate with peritoneal transport. There was no difference in any mediator level between patients receiving conventional and low glucose degradation product solutions. Dialysis effluent IL-6 and COX-2 levels correlate with the concomitant D/P4 and MTAC of creatinine. IL-6 and COX-2 may contribute to the short-term regulation of peritoneal transport.

Understanding Urea Kinetic Factors That Enhance Personalized Hemodialysis Prescription in Children.

Urea dialyzer clearance (KD) has been suggested to be underpredicted from blood flow (QB), dialysate flow (QD), and in vitro mass transfer-area coefficient of urea (KoA) in pediatric hemodialysis (HD) patients using a widely accepted mechanistic equation. We characterize factors that could explain this, assuming that it results from a bias between reported in vitro and actual in vivo KoA. An adult urea kinetic model was scaled to 923 patients aged 1-29 years based on pediatric physiologic knowledge (intercompartmental clearance, volumes of distribution). Using data from 2,676 HD sessions of those patients (pre-/post-HD urea concentrations and HD treatment parameters), mixed effect modeling was applied to estimate individual KoA correction factors (fKoA) required for unbiased KD and post-HD urea concentration predictions in vivo. QD/QB ratio was most strongly associated with individual fKoA estimates (P < 0.001; fKoA = -1%, 18%, and 110% at QD/QB ratios of 1.5, 2, and 5). Additional factors included in the model were filter flux (-12% lower fKoA for low- vs high-flux filters), ultra-filtration rate, and true QB (lower than nominal QB ≥200 ml/min). Of note, high QD/QB ratios used in children ≤6 years were associated with significant underprediction of KD in vivo, with post-HD urea concentrations being 23% lower than expected. In conclusion, dialyzers should be characterized under pediatric conditions where high QD/QB ratios are used. Our model can be used to prevent underestimation of urea clearance, allowing shorter dialysis sessions, higher quality of life, and individualized treatment prescription in children on maintenance HD.

Quantifying the Effect of Plasma Viscosity on In Vivo Dialyzer Performance.

Dialyzer manufacturers characterize performance of their devices based on measurements of clearance using crystalloid solutions. Typically, in vitro dialyzer mass transfer area coefficients for urea (K0A) are substantially higher than values measured in vivo. The reason for this reduction has not been clearly determined. We hypothesized that the known effect of viscosity on reducing solute diffusivity might partially or fully account for this reduction. In vitro dialyzer clearances of urea, glucose, and lactate were measured using crystalloid solutions as well as bovine blood with varying hematocrit and plasma viscosity under a wide range of operating conditions. Viscosities of crystalloid solutions, of blood plasma, and of whole blood were measured at 37°C at a shear rate of 100/s. Diffusivity and relative K0A values (K0Arel) in eight dialyzers were computed for each solute under these different conditions. Plasma was 1.84 times more viscous compared with crystalloid solution (ηrel = 1.84), suggesting a correction multiplier of 1/ηrel = 0.54 for in vivo K0A relative to the in vitro value. Experimental K0Arel at that ηrel was on average reduced to 52% of crystalloid in vitro K0A values. The multiplier 0.52 measured in this study is close to the multiplier 0.55 predicted for average plasma viscosities and also close to the multiplier 0.54 assumed for urea kinetic modeling to provide reasonable urea distribution volumes. The known effect of viscosity on solute diffusivity is therefore sufficient to explain the reduction in dialyzer K0A for urea and glucose in vivo compared with in vitro measurements.

Mass transfer in Spinning Fluids Reactor — Measurement and prediction

Specific mass transfer area (a) and overall volumetric mass transfer coefficient (kLa) are mass transfer parameters commonly used in the description and comparison of various chemical reactors’ constructions. Determination of these was performed for Spinning Fluids Reactor (SFR). Sodium sulfite oxidation in the presence of cobalt ion catalyst was used for the determination of a and kLa. The a and kLa were successful predicted. Overall, the a and kLa is one order of magnitude larger than any gas liquid contactor to date.

Peritoneal protein clearance predicts mortality in peritoneal dialysis patients.

Peritoneal protein clearance has been suggested to be a marker of peritoneal inflammation and systemic endothelial dysfunction. We enrolled 711 consecutive incident PD patients. Baseline peritoneal protein clearance and other clinical information were reviewed. All patients were followed for at least 1year for all-cause and cardiovascular mortality. The average PD effluent protein loss was 6.41 ± 2.16g/day; peritoneal protein clearance was 97.15 ± 41.55mL/day. The average duration of follow-up was 50.8 ± 36.2 months. Multivariate linear regression analysis showed that serum albumin, C-reactive protein, and mass transfer area coefficients of creatinine were independently associated with peritoneal protein clearance. By multivariate Cox regression analysis, age, Charlson comorbidity score, volume of overhydration and peritoneal protein clearance were independent predictors of all-cause mortality. Every 10mL/day increase in peritoneal protein clearance confers 10.4% increase in risk of all-cause mortality (95% confidence interval 2.6-18.7%, p = 0.008). Peritoneal protein clearance was also associated with cardiovascular mortality by univariate analysis, but the association became insignificant after adjusting for confounding factors Cox regression analysis. Baseline peritoneal protein clearance is an independent predictor of all-cause mortality in incident PD patients. Routine measurement of peritoneal protein clearance may facilitate patient risk stratification.

Peritoneal dialysis fluid biocompatibility impact on human peritoneal membrane permeability.

ABSTRACTBackgroundWe have compared the effects of conventional lactate-based peritoneal dialysis fluid (CPDF) with respect to bicarbonate/lactate-based fluid on peritoneal ultrafiltration (UF) and peritoneal permeability, and on variations on gene expression in cells isolated from effluents of patients’ peritoneal bags.MethodsThis was a non-randomized sequential prospective study including all incident peritoneal dialysis (PD) patients (n = 40) recruited in our centre. Peritoneal equilibration tests (PETs) were performed using CPDF or BPDF both containing 2.27% glucose during a 48-h interval in four different sequences. Gene expression variation of selected genes was measured by reverse transcription polymerase chain reaction in mesothelial cells obtained from the total drained fluid during the PET.ResultsIn the overall study, the use of BPDF was associated with significantly lower mass transfer area coefficient for urea and creatinine, longer accelerated peritoneal examination test times for urea and creatinine, lower total pore area available for exchange over diffusion distance and lower UF. There were no differences in the gene expression of aquaporins 1–3, endothelial and inducible nitric oxide synthase (NOS3 and NOS2), or interleukin-6. The SNAIL and E-CADHERIN gene expression normalized ratio was evaluated in peritoneal effluents of cells obtained from CPDF and BPDF. We observed that the SNAIL/E-CADHERIN mRNA ratio decreased when the dialysis sequence started with BPDF and went on to CPDF, but not when the sequence was the opposite.ConclusionThis study shows that those patients who started PD treatment with BPDF were characterized by a better biocompatibility profile. BPDF associates with lower peritoneal permeability to small molecules and lower UF.

Different patterns of inflammatory and angiogenic factors are associated with peritoneal small solute transport and peritoneal protein clearance in peritoneal dialysis patients

BackgroundBoth peritoneal small solute transport and peritoneal protein clearance are closely linked to outcomes in peritoneal dialysis (PD) patients. However, the associated factors of these two components are not fully understood so far. This study aimed to investigate the association between a panel of systemic and peritoneal inflammatory and angiogenic factors and peritoneal solute transport properties.MethodsStable PD patients in PD center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled in present study. Serum and overnight effluent markers including angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), sTie-2, VEGF, IL-6 and IL-10 were determined. Mass transfer area coefficient of creatinine (MTACcr) and peritoneal protein clearance (Prcl) were calculated. Multivariable linear regression was used to examine the association between these markers and MTACcr as well as Prcl.ResultsA total of 320 patients were enrolled in present study, which consisted of 166 (51.9%) males with a mean age of 56.8 ± 14.2 years and a median PD duration of 32.5 (9.0–56.3) months. Multiple regression analyses showed that BSA, history glucose exposure, dialysate IL-6 AR and dialysate Ang-1 AR were independent associated factors of MTACcr, while BSA and serum Ang-1 were independent associated factors of Prcl.ConclusionsMTACcr representing peritoneal small-solute transport and Prcl representing peritoneal large molecular transport are associated with slightly different panels of inflammatory and angiogenic factors.

Mass Transfer Parameters for Packings: Effect of Viscosity

The effect of liquid viscosity (μL) on the effective mass transfer area (ae) and liquid film mass transfer coefficient (kL) of packing must be known to determine packing height. Most existing correlations are based on water and are not applicable to viscous systems. In this work, ae, kL, and gas film mass transfer coefficient (kG) were measured in a 0.43 m ID packed column with 0.5–3 m of packing. Liquid viscosity was varied from 0.8 to 70 mPa·s by adding glycerol to water. Liquid viscosity has an insignificant effect on ae over the range of μL investigated. The total dependence of kL on μL is −0.75, of which −0.35 is indirect influence through diffusivity, and −0.4 is direct influence through liquid turbulence. Universal mass transfer models for packing were developed as functions of packing geometry, operating condition, and fluid property.

Effect of Liquid Viscosity on Mass Transfer Area and Liquid Film Mass Transfer Coefficient for GT-OPTIMPAK 250Y

The viscosity of amine solutions used for post-combustion CO2 capture is significantly greater than water. The effect of liquid viscosity (μL) on both the effective mass transfer area (ae) and the liquid film mass transfer coefficient (kL) of packings is required to predict mass transfer rate and design the absorber and stripper. Existing correlations are mostly based on water so they do not represent the viscosity of amine solvents. In this work, ae and kL were measured in a packed column (0.43 m inner diameter) with 3 meters of GT-OPTIMPAK 250Y. Liquid viscosities of 65, 15, 4, and 1 cP were obtained by adding 85, 65, 44, and 0wt % glycerol to water. The ae was determined by reactive absorption of ambient CO2 into 0.1M sodium hydroxide solution with the absorption rate (kg’) calculated from a kinetic model specific to the viscous system. The kL was determined by air stripping toluene from the liquid. Liquid viscosity does not show significant effect on ae over the range of μL investigated. The total dependence of kL on μL is -0.73 for the packing examined. The variance of μL is the greatest that can be found in open literature with larger scale equipment, and the result with this packing is believed to be qualitatively representative of other structured packings.

The Natural Time Course of Membrane Alterations During Peritoneal Dialysis Is Partly Altered by Peritonitis.

♦ The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦ This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis ("no-peritonitis group") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes ("peritonitis group") during a follow-up of 4 years. ♦ The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and α2-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. ♦ On top of the natural course of peritoneal function, peritonitis episodes to some extent influence the time-course of small-solute and fluid transport-especially the transport of solute-free water. Those modifications increase the risk for overhydration.