Evaluation and characterization of starch nanoparticles for adsorption of urea from dialysates.

Starch nanoparticles (SNPs) was produced from type-A, B and C native starches (corn, potato and Trichosanthes kirilowii pulp starches respectively), via the nanoprecipitation method. The SNPs showed different amylose contents, water contact angles, surface morphologies and urea clearance performances. In this work, to examine the parameters of SNPs that may change the urea adsorption capacity, urea adsorption performance in adsorption environments with different pH values, urea concentrations, and adsorption times was examined. Thereafter, the characteristics of SNPs were tested by water contact angle measurements (WCA), transmission electron microscopy, specific surface area measurements, gel permeation chromatography, and zeta potential analysis. The results showed that the Trichosanthes kirilowii pulp (C) SNPs show better adsorption than the corn (A) and potato (B) SNPs. The hydrophobicity of SNPs promotes the urea adsorption of the SNPs. Using grey relational analysis, it was found that WCA and Mn are the critical parameter affecting the adsorption performance, with WCA and Mn within the ranges of 31-33° and 1900-2100 kDa, respectively, were found to be the conditions for optimal urea adsorption.

Potassium responses to sodium zirconium cyclosilicate in hyperkalemic hemodialysis patients: post-hoc analysis of DIALIZE.

BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an effective and well-tolerated treatment for hyperkalemia in maintenance hemodialysis patients. In post-hoc analyses of the phase 3b DIALIZE study, we examined the spectrum of potassium responses to SZC. METHODS: Post-hoc analyses with SZC and placebo included: the number of long interdialytic interval (LIDI) visits during the 4-week evaluation period where patients attained pre-dialysis serum potassium (sK+) concentrations of 4.0-5.0 and 4.0-5.5 mmol/L; potassium gradient (the difference between pre-dialysis sK+ and dialysate potassium) at days 36, 43, 50, and 57, and change from baseline to the end of treatment (EOT) using categories of potassium gradient (1 to < 2, 2 to < 3, 3 to < 4, and ≥ 4 mmol/L). RESULTS: A greater proportion of patients achieved the ranges of pre-dialysis sK+ concentration with SZC versus placebo for ≥1, ≥ 2, ≥ 3, and 4 LIDI visits over 4 weeks; 23.7 and 48.5% of patients in the SZC group achieved pre-dialysis sK+ concentrations of 4.0-5.0 and 4.0-5.5 mmol/L, respectively, at all 4 LIDI visits. Baseline mean potassium gradient was similar with SZC and placebo. At day 57, mean (standard deviation) potassium gradient was 2.78 (0.08) mmol/L with SZC and 3.52 (0.08) mmol/L with placebo; mean difference (95% confidence interval) was - 0.74 mmol/L (- 0.97 to - 0.52). A greater reduction in potassium gradient category from baseline towards lower-risk categories at EOT was observed with SZC versus placebo. CONCLUSIONS: These analyses expand our knowledge of the spectrum of potassium responses with SZC in hyperkalemic hemodialysis patients. TRIAL REGISTRATION: NCT03303521 .

Presence of galectin-3 in peritoneal dialysate. Does it have a role in the peritoneal membrane inflammatory process?

Peritoneal dialysis (PD) causes structural and functional changes in the peritoneal membrane, which are attributed to local inflammatory process. This study assessed the presence of galectin-3 (Gal-3), a known inflammatory modulator, in dialysate effluent and correlated its levels with markers of inflammatory process. Gal-3 levels in serum and dialysate effluent were measured in prevalent PD patients on morning visits (n = 27) or during peritoneal equilibration tests (PET, n = 16), it association with clinical and laboratory parameters, including dialysate/plasma creatinine (D/P creatinine) and interleukin-6 (IL-6) levels was analysed. Gal-3 levels in dialysate effluent correlated with D/P creatinine (0.663, p = 0.005) and dialysate effluent IL-6 levels (0.674, p = 0.002), but not with serum Gal-3 levels or dialysis vintage. Patients who were high transporters had higher Gal-3 levels in dialysate effluent, as compared to lower transporters. In multivariate regression analysis, dialysate IL-6 level was the strongest predictor of dialysate Gal-3 levels. This study found Gal-3 in dialysate effluent correlated with D/P creatinine and dialysate IL-6 levels. These findings may imply that Gal-3 has a role in the intraperitoneal inflammatory process. However, this needs to be investigated further.

Comparison of Isotonic Activation of Cell Volume Regulation in Rat Peritoneal Mesothelial Cells and in Kidney Outer Medullary Collecting Duct Principal Cells.

In disease states, mesothelial cells are exposed to variable osmotic conditions, with high osmotic stress exerted by peritoneal dialysis (PD) fluids. They contain unphysiologically high concentrations of glucose and result in major peritoneal membrane transformation and PD function loss. The effects of isotonic entry of urea and myo-inositol in hypertonic (380 mOsm/kg) medium on the cell volume of primary cultures of rat peritoneal mesothelial cells and rat kidney outer medullary collecting duct (OMCD) principal cells were studied. In hypertonic medium, rat peritoneal mesothelial cells activated a different mechanism of cell volume regulation in the presence of isotonic urea (100 mM) in comparison to rat kidney OMCD principal cells. In kidney OMCD cells inflow of urea into the shrunken cell results in restoration of cell volume. In the shrunken peritoneal mesothelial cells, isotonic urea inflow caused a small volume increase and activated regulatory volume decrease (RVD). Isotonic myo-inositol activated RVD in hypertonic medium in both cell types. Isotonic application of both osmolytes caused a sharp increase of intracellular calcium both in peritoneal mesothelial cells and in kidney OMCD principal cells. In conclusion, peritoneal mesothelial cells exhibit RVD mechanisms when challenged with myo-inositol and urea under hyperosmolar isotonic switch from mannitol through involvement of calcium-dependent control. Myo-inositol effects were identical with the ones in OMCD principal cells whereas urea effects in OMCD principal cells led to no RVD induction.

An improved method to estimate absolute blood volume based on dialysate dilution.

Online hemodiafiltration machines equipped with a blood volume monitor and the possibility to rapidly infuse exact amounts of ultrapure dialysate into the extracorporeal circulation can be used to determine absolute blood volume in clinical practice. The aim of the present study was to evaluate the reproducibility of such measurements. Intra-individual reproducibility was evaluated in four measurements taken in hourly intervals within the same dialysis treatment. Ten patients were studied. Absolute blood volumes measured at the beginning and after 1 hour of dialysis were significantly different (80.6 ± 14.5 and 63.9 ± 14.3 mL/kg, P < .001) and highly reproducible between the last three measurements (63.9 ± 14.3, 61.4 ± 13.8, and 60.9 ± 13.9 mL/kg, P = n.s.). Measurement of absolute blood volume after 1 hour of treatment is more precise than earlier measurements and might be better suited for guidance of ultrafiltration.

Relationship between measured and prescribed dialysate sodium in haemodialysis: a systematic review and meta-analysis.

BACKGROUND: Dialysate sodium (DNa) prescription policy differs between haemodialysis (HD) units, and the optimal DNa remains uncertain. We sought to summarize the evidence on the agreement between prescribed and delivered DNa, and whether the relationship varied according to prescribed DNa. METHODS: We searched MEDLINE and PubMed from inception to 26 February 2020 for studies reporting measured and prescribed DNa. We analysed results reported in aggregate with random-effects meta-analysis. We analysed results reported by individual sample, using mixed-effects Bland-Altman analysis and linear regression. Pre-specified subgroup analyses included method of sodium measurement, dialysis machine manufacturer and proportioning method. RESULTS: Seven studies, representing 908 dialysate samples from 10 HD facilities (range 16-133 samples), were identified. All but one were single-centre studies. Studies were of low to moderate quality. Overall, there was no statistically significant difference between measured and prescribed DNa {mean difference = 0.73 mmol/L [95% confidence interval (CI) -1.12 to 2.58; P = 0.44]} but variability across studies was substantial (I2 = 99.3%). Among individually reported samples (n = 295), measured DNa was higher than prescribed DNa by 1.96 mmol/L (95% CI 0.23-3.69) and the 95% limits of agreement ranged from -3.97 to 7.88 mmol/L. Regression analysis confirmed a strong relationship between prescribed and measured DNa, with a slope close to 1:1 (ß = 1.16, 95% CI 1.06-1.27; P < 0.0001). CONCLUSIONS: A limited number of studies suggest that, on average, prescribed and measured DNa are similar. However, between- and within-study differences were large. Further consideration of the precision of delivered DNa is required to inform rational prescribing.

Feasibility of Citrate Dialysis in Hyponatremia: A Case Series.

BACKGROUND: Correcting hyponatremia too quickly can lead to osmotic demyelination syndrome. During citrate dialysis, a significant sodium load is brought to the prefilter. We reviewed the impact of this sodium load on the evolution of sodium levels in patients undergoing continuous renal replacement therapy with citrate anticoagulation. MATERIALS AND METHODS: The medical records of 5 patients with hyponatremia who received dialysis with citrate anticoagulation, over a 10-year period, were reviewed. The sodium of the dialysate and of the reinjection fluid was adapted according to the serum sodium level recommended by the guidelines of the time. Data from the first 24 h after initiation of dialysis was evaluated. RESULTS: The difference in serum sodium levels between day 1 and day 2 was statistically significant, with a rise of 7.8 ± 3.7 mmol/L. DISCUSSION: The mean serum sodium increase in our series of patients did not exceed the increase of 10-12 mEq/L/day permitted by the guidelines. The excess sodium was absorbed by the filter. CONCLUSION: In this small series of patients, with adjustment of the sodium concentration of dialysate and reinjection fluid, the use of citrate was found to be safe.

Intradialytic Calcium Kinetics and Cardiovascular Disease in Chronic Hemodialysis Patients.

BACKGROUND/OBJECTIVE: Calcium loading has been associated with cardiovascular risk in hemodialysis (HD) patients. However, it remains to be elucidated whether alterations of intradialytic calcium buffering add to the increased cardiovascular disease burden in this high-risk population. METHODS: Intradialytic calcium kinetics was evaluated in a cross-sectional observational study by measuring dialysate-sided ionized calcium mass balance (iCaMB), calcium buffer capacity, and change in serum calcium levels in 40 chronic HD patients during a routine HD session. A dialysate calcium of 3.5 mEq/L was used to adequately challenge calcium buffer mechanisms. Aortic pulse wave velocity and serum osteocalcin levels were measured prior to the HD session. Presence of cardiovascular disease and diabetes was assessed. RESULTS: The mean dialysate-sided iCaMB, extracellular fluid ionized calcium mass gain, and buffered ionized calcium mass were 469 (±154), 111 (±49), and 358 (±145) mg/HD, respectively. The mean ionized serum calcium increase (∆iCa) was 0.42 (±0.14) mEq/L per HD. The mean intradialytic calcium buffer capacity was 73 (±18)%. Multivariate regression analysis revealed significant independent association of (1) iCaMB with the dialysate-to-blood calcium gradient at HD start and (2) intradialytic calcium buffer capacity with undercarboxylated osteocalcin. The presence of coronary heart disease was associated with higher ∆iCa but not iCaMB in the multivariate model. CONCLUSIONS: In line with our proof-of-concept study, we provide clinical evidence for a rapidly accessible and exchangeable calcium pool involved in intradialytic calcium regulation and for the role of osteocalcin as a potential biomarker. Our findings argue for evaluating the prognostic potential of intradialytic calcium kinetics in prospective clinical trials.

Validation and applicability of an alternative method for dialysis water and dialysate quality analysis / Validação e aplicabilidade de um método alternativo para análise da qualidade da água e do dialisato em diálise

ABSTRACT Introduction: In hemodialysis, patients are exposed to a large volume of water, which may lead to fatal risks if not meeting quality standards. This study aimed to validate an alternative method for monitoring microbiological quality of treated water and assess its applicability in dialysis and dialysate analysis, to allow corrective actions in real-time. Methods: Validation and applicability were analyzed by conventional and alternative methods. For validation, E. coli standard endotoxin was diluted with apyrogenic water in five concentrations. For the applicability analysis, treated water for dialysis was collected from different points in the treatment system (reverse osmosis, drainage canalization at the storage tank bottom, reuse, and loop), and dialysate was collected from four machines located in different rooms in the hemodialysis sector. Results: The validation results were in accordance with the Brazilian Pharmacopoeia acceptance criteria, except for the last two concentrations analyzed. In addition, the ruggedness criterion performed under the US Pharmacopoeia was in agreement with the results. Discussion: A limiting factor in the applicability analysis was the absence of the endotoxin maximum permitted level in dialysate by the Brazilian legislation. When comparing the analysis time, the alternative method was more time-consuming than the conventional one. This suggests that the alternative method is effective in the case of few analyses, that is, real-time analyses, favoring corrective actions promptly. On the other hand, it does not support the implementation of the alternative method in a laboratory routine due to the high demand for analyses.

RESUMO Introdução: Na hemodiálise, os pacientes são expostos a um grande volume de água, o que pode levar a riscos fatais se não cumprir com padrões de qualidade. Este estudo teve como objetivo validar um método alternativo para monitorar a qualidade microbiológica da água tratada e avaliar sua aplicabilidade em análises de diálise e dialisato, para permitir ações corretivas em tempo real. Métodos: A validação e aplicabilidade foram analisadas por métodos convencionais e alternativos. Para validação, a endotoxina padrão de E. coli foi diluída com água apirogênica em cinco concentrações. Para a análise de aplicabilidade, a água tratada para diálise foi coletada em diferentes pontos do sistema de tratamento (osmose reversa, canalização de drenagem no fundo do tanque de armazenamento, reutilização e circuito) e o dialisato foi coletado em quatro máquinas localizadas em diferentes salas do setor de hemodiálise. Resultados: Os resultados da validação obedeceram aos critérios de aceitação da Farmacopeia Brasileira, com exceção das duas últimas concentrações analisadas. Além disso, o critério de robustez realizado sob a Farmacopeia dos EUA estava de acordo com os resultados. Discussão: Um fator limitante na análise de aplicabilidade foi a ausência do nível máximo permitido de endotoxina no dialisato pela legislação brasileira. Ao comparar o tempo de análise, o método alternativo consumiu mais tempo que o convencional. Isso sugere que o método alternativo é eficaz no caso de poucas análises, ou seja, análises em tempo real, favorecendo ações corretivas imediatamente. Por outro lado, não suporta a implementação do método alternativo em uma rotina de laboratório devido à alta demanda por análises.

Validation and applicability of an alternative method for dialysis water and dialysate quality analysis.

INTRODUCTION: In hemodialysis, patients are exposed to a large volume of water, which may lead to fatal risks if not meeting quality standards. This study aimed to validate an alternative method for monitoring microbiological quality of treated water and assess its applicability in dialysis and dialysate analysis, to allow corrective actions in real-time. METHODS: Validation and applicability were analyzed by conventional and alternative methods. For validation, E. coli standard endotoxin was diluted with apyrogenic water in five concentrations. For the applicability analysis, treated water for dialysis was collected from different points in the treatment system (reverse osmosis, drainage canalization at the storage tank bottom, reuse, and loop), and dialysate was collected from four machines located in different rooms in the hemodialysis sector. RESULTS: The validation results were in accordance with the Brazilian Pharmacopoeia acceptance criteria, except for the last two concentrations analyzed. In addition, the ruggedness criterion performed under the US Pharmacopoeia was in agreement with the results. DISCUSSION: A limiting factor in the applicability analysis was the absence of the endotoxin maximum permitted level in dialysate by the Brazilian legislation. When comparing the analysis time, the alternative method was more time-consuming than the conventional one. This suggests that the alternative method is effective in the case of few analyses, that is, real-time analyses, favoring corrective actions promptly. On the other hand, it does not support the implementation of the alternative method in a laboratory routine due to the high demand for analyses.

The efficacy and safety of low dialysate sodium levels for patients with maintenance haemodialysis: A systematic review and meta-analysis.

BACKGROUND & AIM: Fluid overload and hypertension frequently results in cardiovascular disease, which is one of the leading causes of death in dialysis patients. It is plausible that low dialysate [Na+] may decrease total body sodium content, thereby reducing fluid overload and hypertension, and ultimately reducing cardiovascular disease morbidity and mortality. This meta-analysis was designed to evaluate the efficacy and safety of using a low (<138 mM) dialysate [Na+] for maintenance haemodialysis (HD) patients. METHODS: We searched the Cochrane Library, PubMed, EMBASE, Web of Science up to August 22, 2019. Randomised controlled trials (RCTs), both parallel and cross-over, of low (<138 mM) versus neutral (138-140 mM) or high (>140 mM) dialysate [Na+] for maintenance HD patients were included. Mean difference (MD), risk ratio (RR) and 95% confidence interval (CI) values were estimated to compare the outcomes. Two reviewers extracted data and assessed trial quality independently. All statistical analyses were performed using the standard statistical procedures of RevMan 5.2. RESULTS: 12 Randomised controlled trials with 390 patients were included in this meta-analysis. Of these studies, three studies were parallel group, and the remaining nine were crossover. Compared to neutral or high dialysate [Na+], low dialysate [Na+] reduced dialysis mean arterial pressure (MAP) with a pooled MD of -3.38 mmHg (95% CI -4.57 to -2.19; P < 0.00001), reduced interdialytic weight gain with a pooled MD of -0.35 kg (95% CI -0.51 to -0.18; P < 0.0001), reduced predialysis serum [Na+] with a pooled MD of -2.62 mM (95% CI -3.59 to -1.66; P < 0.00001). In contrast, low dialysate [Na+] increased intradialytic hypotension events with a pooled RR of 1.54 (95% CI 1.16 to 2.05; P = 0.003), increased the incidence of intradialytic cramps with a pooled RR of 1.77 (95% CI 1.15 to 2.73; P = 0.01). However, no difference was found between lower and higher dialysate [Na+] in systolic blood pressure and diastolic blood pressure. CONCLUSIONS: Though our pooled result indicated that low dialysate [Na+] reduced MAP, interdialytic weight gain and predialysis serum [Na+] significantly, it also indicated that low dialysate [Na+] could increase the incidence of intradialytic hypotension and intradialytic cramps events. Considering the contradiction in efficacy and safety of low dialysate [Na+] in our analysis, future larger and up-to-date definitive studies are needed to evaluate the medium to long-term effects of low sodium levels in dialysis fluid, and better inform clinical practice.

Longitudinal Changes of NF-κB 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.

Evaluation of T2Candida Panel for detection of Candida in peritoneal dialysates.

Fungal peritonitis in the peritoneal dialysis population is difficult to diagnose promptly due to the inherently slow cultivation-based methods currently required for identification of peritonitis pathogens. Because of the moderate risk for severe complications, the need for rapid diagnostics is considerable. One possible solution to this unmet need is the T2Candida Panel, a new technology designed to detect the most common pathogenic Candida spp. directly from whole blood specimens in as little as a few hours. We hypothesized that this technology could be applied to the detection of Candida in peritoneal dialysate, a matrix not currently approved by the Food and Drug Administration for testing by this system. Remnant dialysate samples from three healthy (noninfected) pediatric peritoneal dialysis patients were spiked with Candida glabrata, serially diluted, and tested in triplicate with unaltered dialysate specimens. The assay detected C. glabrata in 100% of spiked dialysate samples across the full spectrum of dilutions tested, and no assay inhibition or cross-reactivity was noted. These findings suggest one of possibly more applications of this technology. The positive clinical implications of this test will continue to be realized as its use is validated in peritoneal dialysate and other patient specimen types.

End-Stage Renal Disease Patients Lose a Substantial Amount of Amino Acids during Hemodialysis.

BACKGROUND: Poor nutritional status is frequently observed in end-stage renal disease patients and associated with adverse clinical outcomes and increased mortality. Loss of amino acids (AAs) during hemodialysis (HD) may contribute to protein malnutrition in these patients. OBJECTIVE: We aimed to assess the extent of AA loss during HD in end-stage renal disease patients consuming their habitual diet. METHODS: Ten anuric chronic HD patients (mean ± SD age: 67.9 ± 19.3 y, BMI: 23.2 ± 3.5 kg/m2), undergoing HD 3 times per week, were selected to participate in this study. Spent dialysate was collected continuously and plasma samples were obtained directly before and after a single HD session in each participant. AA profiles in spent dialysate and in pre-HD and post-HD plasma were measured through ultra-performance liquid chromatography to determine AA concentrations and, as such, net loss of AAs. In addition, dietary intake before and throughout HD was assessed using a 24-h food recall questionnaire during HD. Paired-sample t tests were conducted to compare pre-HD and post-HD plasma AA concentrations. RESULTS: During an HD session, 11.95 ± 0.69 g AAs were lost via the dialysate, of which 8.26 ± 0.46 g were nonessential AAs, 3.69 ± 0.31 g were essential AAs, and 1.64 ± 0.17 g were branched-chain AAs. As a consequence, plasma total and essential AA concentrations declined significantly from 2.88 ± 0.15 and 0.80 ± 0.05 mmol/L to 2.27 ± 0.11 and 0.66 ± 0.05 mmol/L, respectively (P < 0.05). AA profiles of pre-HD plasma and spent dialysate were similar. Moreover, AA concentrations in pre-HD plasma and spent dialysate were strongly correlated (Spearman's ρ = 0.92, P < 0.001). CONCLUSIONS: During a single HD session, ∼12 g AAs are lost into the dialysate, causing a significant decline in plasma AA concentrations. AA loss during HD can contribute substantially to protein malnutrition in end-stage renal disease patients. This study was registered at the Netherlands Trial Registry (NTR7101).

Single-species (bacterial, fungal, or mycobacterial) biofilms or dual-species (mycobacterial-fungal) biofilms formed in dialysis fluids.

Continuous hemodialysis system monitoring is necessary to prevent microorganism growth and health problems. This study evaluates single- and dual-species biofilm formation in microtiter plates by using dialysis solutions under aerobiosis or 5% CO2 atmosphere. Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Candida parapsilosis sensu lato, and Mycobacterium smegmatis produce single-species biofilms in all dialysis solutions in both oxygenation conditions. Dual-species biofilm cultures grown at 5% CO2 atmosphere and in dialysate containing glucose reveal that M. smegmatis benefits from its association with C. parapsilosis. The dialysate and its constituent solutions support the growth of all the mono-species and the inter-kingdom mycobacterial/yeast biofilms in both aerobiosis and microaerophilic conditions.

Estimation of residual renal function using beta-trace protein: Impact of dialysis procedures.

Beta-trace protein (BTP), a low molecular weight protein of 23-29 kDa, has been proposed as a promising biomarker to estimate residual renal function (RRF) in patients on maintenance hemodialysis (HD). Indeed, BTP is cleared by native kidney but not during conventional HD session. By contrast, the removal rate of BTP using convective processes (mainly hemodiafiltration [HDF]) and peritoneal dialysis (PD) has been little or not investigated. Therefore, an aim of this study was to evaluate the impact of dialysis procedures (high-flux HD, on-line post-dilution HDF and PD) on BTP removal in comparison with beta-2 microglobulin (B2M) and cystatin C (CYSC) removals after a single session. In addition, the ability of BTP to predict RRF in PD was assessed. This observational cross-sectional study included a total of 82 stable chronic kidney disease patients, 53 patients were on maintenance dialysis (with n = 26 in HD and n = 27 in HDF) and 29 were on PD. Serum concentrations of BTP, B2M, and CYSC were measured (a) before and after a single dialysis session in HD and HDF anuric patients to calculate reduction percentages, (b) in serum, 24-hour-dialysate and 24-hour-urine in PD patients to compute total, peritoneal, and urinary clearance. RRF was estimated using four equations developed for dialysis patients without urine collection and compared to the mean of the urea and creatinine clearances in PD. The concentrations of the three studied molecules were significantly reduced (P < .001) after dialysis session with significantly higher reduction ratio using HDF compared to HD modality (P < .001): BTP 49.3% vs 17.5%; B2M 82.3% vs 69.7%; CYSC 77.4% vs 66% in HDF and HD, respectively. In non-anuric PD patients, B2M and CYSC were partly removed by peritoneal clearance (72.3% and 57.6% for B2M and CYSC, respectively). By contrast, BTP removal by the peritoneum was negligible and a low bias for the BTP-based equation to estimate RRF (-1.4 mL/min/1.73 m2 ) was calculated. BTP is significantly removed by high-flux HD or HDF, thereby compromising its use to estimate RRF. By contrast, BTP appears as a promising biomarker to estimate RRF in PD patients since it is not affected by peritoneal clearance, unlike B2M and CYSC, and it is well correlated to RRF.

Multipoint dilution hemofiltration: A new technology for maximum convective clearance.

Convection-based renal replacement therapies (RRTs) have the potential to improve patient outcomes when compared to diffusion-based RRT such as hemodialysis (HD), but have limited clearance rates. We propose and characterize multipoint dilution hemofiltration (MPD-HF), a purely convective blood purification technology which removes the fundamental filtration limit associated with convective RRT resulting in clearance rates on par with HD. In MPD-HF, filtration of liquid and solutes occurs along the length of the hollow fibers that convey the blood, and substitution fluid is pushed into the fibers at multiple points along their length. Since multiple filtration and dilution steps are contained within one pass of the blood through the hollow fiber, the fraction of fluid that can be filtered may be increased to allow a high clearance rate that removes a wide range of toxins. In vitro tests yielded an average steady-state filtrate fraction of 68%, exceeding commercial HDF cartridge filtrate fractions by a factor of approximately 3. The molecular weights of molecules cleared spans up to the cutoff of 66 kDa for albumin.

Serial measurement of electrolyte and citrate concentrations in blood-primed continuous hemodialysis circuits during closed-circuit dialysis.

BACKGROUND: For continuous renal replacement therapy in small infants, due to the large extracorporeal volume involved, blood priming can be necessary to prevent hypotension and hemodilution. Because packed red blood cells (RBCs) have high levels of potassium and citrate, closed-circuit dialysis is often performed. We assessed the metrics of closed-circuit dialysis and serial citrate concentration changes. METHODS: We performed dialysis of closed circuits primed with expired human packed RBC solution and 5% albumin. Blood and dialysate flow rates were 70 and 33.3 mL/min, respectively. The extracorporeal volume was 70 mL. We measured pH, electrolytes, and citrate in the closed circuit every 3 min for 15 min. We also assessed the adequacy of closed-circuit dialysis using the formula: [dialysate flow rate (mL/min) × time of dialysis (min)]/extracorporeal volume (mL) and we assessed the correlation between citrate and ionized calcium concentrations. RESULTS: To reach normal concentrations of sodium, potassium, and chloride, 2.4 times as much dialysate fluid as extracorporeal volume was needed. In contrast, for ionized calcium, bicarbonate, and citrate, 3.8 times as much dialysate fluid as extracorporeal volume was required. By simple linear regression analysis, the concentration of citrate was significantly correlated with that of ionized calcium. CONCLUSIONS: For closed-circuit dialysis using an RBC solution, the formula [dialysate flow rate (mL/min) × time of dialysis (min)]/extracorporeal volume (mL) would be a better parameter to estimate efficacy, compared with other metrics. Additionally, the citrate concentration can be readily estimated from the ionized calcium concentration during closed-circuit dialysis.

[Risk analysis and validation of the process for producing the substitution fluid for online hemodiafiltration]. / Analyse des risques et validation du procédé de production du liquide de substitution de la technique d'hémodiafiltration en ligne.

INTRODUCTION: Online hemodiafiltration is a technique of dialysis with many advantages, but its use is limited because of the lack of control of microbiological risks. This work conducts a risk analysis of the process for producing substitution liquid for online hemodiafiltration and validates this process from a microbiological point of view. MATERIAL AND METHOD: The risk analysis was carried out following the approach of analysing failure modes, their effects and their criticalities. It identified the "worst case" of the production process being studied. For the validation of this process, we used the limulus amoebocytes lysate assay for bacterial endotoxins and the membrane filtration test for sterility control. RESULTS: We identified 17 failure modes, 13 of which were acceptable. Failure modes that exceeded the acceptability threshold were defined as "worst cases". Sterility monitoring and endotoxin testing, conducted in the "worst case", verified the microbiological quality of the liquid produced to the required standards and subsequently validated the process used. DISCUSSION: This approach has resulted in the identification of as many failure modes as possible. Validating in "worst case" is an extreme challenge to the process and its success provides a sufficient basis to conclude that the technique is safe and, therefore, to validate the process. CONCLUSION: This work has enabled us to validate our production process in extreme cases to promote safer use of the technique.

Portable Microfluidic Biosensing System for Real-Time Analysis of Microdialysate in Transplant Kidneys.

Currently, there is a severe shortage of donor kidneys that are fit for transplantation, due in part to a lack of adequate viability assessment tools for transplant organs. This work presents the integration of a novel wireless two-channel amperometric potentiostat with microneedle-based glucose and lactate biosensors housed in a 3D printed chip to create a microfluidic biosensing system that is genuinely portable. The wireless potentiostat transmits data via Bluetooth to an Android app running on a tablet. The whole miniaturized system is fully enclosed and can be integrated with microdialysis to allow continuous monitoring of tissue metabolite levels in real time. We have also developed a wireless portable automated calibration platform so that biosensors can be calibrated away from the laboratory and in transit. As a proof of concept, we have demonstrated the use of this portable analysis system to monitor porcine kidneys for the first time from organ retrieval, through warm ischemia, transportation on ice, right through to cold preservation and reperfusion. The portable system is robust and reliable in the challenging conditions of the abattoir and during kidney transportation and can detect clear physiological changes in the organ associated with clinical interventions.