Vancomycin and daptomycin dosing recommendations in patients receiving home hemodialysis using Monte Carlo simulation.

BACKGROUND: Few drug dosing recommendations for patients receiving home hemodialysis (HHD) have been published which has hindered the adoption of HHD. HHD regimens vary widely and differ considerably from conventional, thrice weekly, in-center hemodialysis in terms of treatment frequency, duration and blood and dialysate flow rates. Consequently, vancomycin and daptomycin clearances in HHD are also likely to be different, consequently HHD dosing regimens must be developed to ensure efficacy and minimize toxicity when these antibiotics are used. Many HHD regimens are used clinically, this study modeled ten common HHD regimens and determined optimal vancomycin and daptomycin dosing for each HHD regimen. METHODS: Monte Carlo simulations using pharmacokinetic data derived from the literature and demographic data from a large HHD program treating patients with end stage kidney disease were incorporated into a one-compartment pharmacokinetic model. Virtual vancomycin and daptomycin doses were administered post-HHD and drug exposures were determined in 5,000 virtual patients receiving ten different HHD regimens. Serum concentration monitoring with subsequent dose changes was incorporated into the vancomycin models. Pharmacodynamic target attainment rates were determined for each studied dose. The lowest possible doses that met predefined targets in virtual patients were chosen as optimal doses. RESULTS: HHD frequency, total dialysate volumes and HHD durations influenced drug exposure and led to different dosing regimens to meet targets. Antibiotic dosing regimens were identified that could meet targets for 3- and 7-h HHD regimens occurring every other day or 4-5 days/week. HHD regimens with 3-day interdialytic periods required higher doses prior to the 3-day period. The addition of vancomycin serum concentration monitoring allowed for calculation of necessary dosing changes which increased the number of virtual subjects meeting pharmacodynamic targets. CONCLUSIONS: Doses of vancomycin and daptomycin that will meet desired pharmacodynamic targets in HHD are dependent on patient and HHD-specific factors. Doses used in conventional thrice weekly hemodialysis are unlikely to meet treatment goals. The antibiotic regimens paired with the HHD parameters studied in this analysis are likely to meet goals but require clinical validation.

The role of segmental bioelectrical impedance technique in the assessment of intraperitoneal ultrafiltration volume with peritoneal dialysis patients.

OBJECTIVE: To investigate the role of segmental bioelectrical impedance technique (SBIA) in the assessment of intraperitoneal ultrafiltration volume with peritoneal dialysis patients. METHOD: We selected the patients at the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University and measured the segmental bioelectrical impedance by a German Fresenius body composition analyzer (the Fresenius whole body composition measurement (BCM) machine was used as a segmental machine in this study). An alternating current (5 kHz, 0.05-0.7 mA) was continuously released during the measurement. The released current penetrated the peritoneal cavity on both sides of the body, from which the segmental resistance at a frequency of 5 kHz was obtained from the multifrequency data (R5/Ω). Baseline BIA measurements were initiated after the patient entered the supine position for 5-10 min, then dialysate was instilled into the peritoneal cavity. BIA measurements were performed at 10-min intervals during the retention of dialysate in the abdomen and finally ended when dialysate drainage was complete. Real-time intraperitoneal volume estimated by SBIA (IPVSBIA)and ultrafiltration volume estimated by SBIA(UFVSBIA) was calculated. At the same time, the actual ultrafiltration volume at the end of peritoneal dialysis was weighed and measured (UFVMEA). RESULTS: A total of 30 patients were included in the study, 9 patients withdrew from the study due to subjective factors during the measurement process, and 21 patients completed the study. The correlation coefficient R2 of UFVSBIA and UFVMEA was 0.21 (p < 0.05). Bland-Altman analysis showed that the bias of UFVSBIA to the actual UFVMEA was 0.12 L, and the 95% agreement limit was between -0.5 L and 0.74 L, which confirmed that UFVSBIA measured by electrical impedance method and UFVMEA measured by weighing method were in good agreement. The time required to reach the maximum ultrafiltration volume (UFVSBIA) was 108 ± 68 min, and the mean value of the maximum ultrafiltration volume (Max UFVSBIA) was 1.16 ± 0.60 L. CONCLUSION: The segmental bioelectrical impedance technique can be used to assess the intraperitoneal ultrafiltration volume of peritoneal dialysis patients in real-time and effectively. This method may guide the dialysis fluid retention time and the maximum ultrafiltration volume in PD patients.

Renal Embolization-Induced Uremic Swine Model for Assessment of Next-Generation Implantable Hemodialyzers.

Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial embolization is a non-invasive approach to near-total nephrectomy that preserves retroperitoneal anatomy for device implants. Silicon nanopore membranes (SNM) are efficient blood-compatible membranes that enable novel approaches to RRT. Yucatan minipigs underwent staged bilateral renal arterial embolization to induce renal failure, managed by intermittent hemodialysis. A small-scale arteriovenous SNMHD prototype was implanted into the retroperitoneum. Dialysate catheters were tunneled externally for connection to a dialysate recirculation pump. SNMHD clearance was determined by intermittent sampling of recirculating dialysate. Creatinine and urea clearance through the SNMHD were 76-105 mL/min/m2 and 140-165 mL/min/m2, respectively, without albumin leakage. Normalized creatinine and urea clearance measured in the SNMHD may translate to a fully implantable clinical-scale device. This pilot study establishes a path toward therapeutic testing of the clinical-scale SNMHD and other implantable RRT devices.

Personalized Management of Sodium and Volume Imbalance in Hemodialysis to Mitigate High Costs of Hospitalization.

The primary objective of hemodialysis (HD) is lowering concentrations of organic uremic toxins that accumulate in blood in end-stage kidney disease (ESKD) and redress imbalances of inorganic compounds in particular sodium and water. Removal by ultrafiltration of excess fluid that has accumulated during the dialysis-free interval is a vital aspect of each HD session. Most HD patients are volume overloaded, with ∼25% of patients having severe (>2.5 L) fluid overload (FO). The potentially serious complications of FO contribute to the high cardiovascular morbidity and mortality observed in the HD population. Weekly cycles imposed by the schedule of HD treatments create a deleterious and unphysiological "tide phenomenon" marked by sodium-volume overload (loading) and depletion (unloading). Fluid overload-related hospitalizations are frequent and costly, with average cost estimates of $ 6,372 per episode, amounting to some $ 266 million total costs over a 2-year period in a US dialysis population. Various strategies (e.g., dry weight management or use of fluids with different sodium concentrations) have been attempted to rectify FO in HD patients but have met with limited success largely due to imprecise and cumbersome, or costly, approaches. In recent years, conductivity-based technologies have been refined to actively restore sodium and fluid imbalance and maintain the predialysis plasma sodium set point (plasma tonicity) of each patient. By automatically controlling the dialysate-plasma sodium gradient based on the specific patient needs throughout a session, an individualized sodium dialysate prescription can be delivered. Maintaining precise sodium mass balance helps better control of blood pressure, reduces FO, and thus tends to prevent hospitalization for congestive heart failure. We present the case for personalized salt and fluid management via a machine-integrated sodium management tool. Results from proof-of-principle clinical trials indicate that the tool enables individualized sodium-fluid volume control during each HD session. Its application in routine clinical practice has the potential to mitigate the substantial economic burden of hospitalizations attributed to volume overload complications in HD. Additionally, such a tool would contribute toward reduced symptomology and dialysis-induced multiorgan damage in HD patients and to improving their treatment perception and quality of life which matters most to patients.

The European Green Deal and nephrology: a call for action by the European Kidney Health Alliance.

The world faces a dramatic man-made ecologic disaster and healthcare is a crucial part of this problem. Compared with other therapeutic areas, nephrology care, and especially dialysis, creates an excessive burden via water consumption, greenhouse gas emission and waste production. In this advocacy article from the European Kidney Health Alliance we describe the mutual impact of climate change on kidney health and kidney care on ecology. We propose an array of measures as potential solutions related to the prevention of kidney disease, kidney transplantation and green dialysis. For dialysis, several proactive suggestions are made, especially by lowering water consumption, implementing energy-neutral policies, waste triage and recycling of materials. These include original proposals such as dialysate regeneration, dialysate flow reduction, water distillation systems for dialysate production, heat pumps for unit climatization, heat exchangers for dialysate warming, biodegradable and bio-based polymers, alternative power sources, repurposing of plastic waste (e.g. incorporation in concrete), registration systems of ecologic burden and platforms to exchange ecologic best practices. We also discuss how the European Green Deal offers real potential for supporting and galvanizing these urgent environmental changes. Finally, we formulate recommendations to professionals, manufacturers, providers and policymakers on how this correction can be achieved.

Switching from high-flux dialysis to hemodiafiltration: Cost-consequences for patients, providers, and payers.

Hemodiafiltration (HDF) achieves a more efficient reduction of the uremic toxic load compared to standard high-flux hemodialysis (HF-HD) by virtue of the combined diffusive and convective clearances of a broad spectrum of uremic retention solutes. Clinical trials and registry data suggest that HDF improves patient outcomes. Despite the acknowledged need to improve survival rates of dialysis patients and the survival benefit HDF offers, there is little to no utilization in some countries (such as the US) in prescribing HDF to their patients. In this analysis, we present the healthcare value-based case for HDF (relative to HF-HD) from the patient, provider, and payor perspectives. The improved survival and reduced morbidity observed in studies conducted outside the US, as well as the reduced hospitalization, are attractive for each stakeholder. We also consider the potential barriers to greater utilization of HDF therapies, including unfounded concerns regarding additional costs of HDF, e.g., for the preparation and microbial testing of quality of substitution fluids. Ultrapure fluids are easily attainable and prepared from dialysis fluids using established "online" (OL) technologies. OL-HDF has matured to a level whereby little additional effort is required to safely implement it as all modern machine systems are today equipped with the OL-HDF functionality. Countries already convinced of the advantages of HF-HD are thus well positioned to make the transition to OL-HDF to achieve further clinical and associated economic benefits. Healthcare systems struggling to cope with the increasing demand for HD therapies would therefore, like patients, be beneficiaries in the long term with increased usage of OL-HDF for end stage kidney disease patients.

Assessment of the size selectivity of peritoneal permeability by the restriction coefficient to protein transport.

Transport of serum proteins from the circulation to peritoneal dialysate in peritoneal dialysis patients mainly focused on total protein. Individual proteins have hardly been studied. We determined serum and effluent concentrations of four individual proteins with a wide molecular weight range routinely in the standardised peritoneal permeability analysis performed yearly in all participating patients. These include ß2-microglobulin, albumin, immunoglobulin G and α2-macroglobulin. The dependency of transport of these proteins on their molecular weight and diffusion coefficient led to the development of the peritoneal protein restriction coefficient (PPRC), which is the slope of the relation between the peritoneal clearances of these proteins and their free diffusion coefficients in water, when plotted on a double logarithmic scale. The higher the PPRC, the more size restriction to transport. In this review, we discuss the results obtained on the PPRC under various conditions, such as effects of various osmotic agents, vasoactive drugs, peritonitis and the hydrostatic pressure gradient. Long-term follow-up of patients shows an increase of the PPRC, the possible causes of which are discussed. Venous vasculopathy of the peritoneal microcirculation is the most likely explanation.

Assessment of an Automatic Hot Water Sterilizing System-Equipped Dialysis Supply Device's Circuit Degradation, 7 Years Postinstallment.

At most dialysis clinics in Japan, a central dialysis fluid delivery system (CDDS) is used primarily to provide consistent treatment to patients. We incorporated hot water disinfection to a CDDS over a 7 year period, after which we assessed the dialysis purification levels. We observed that adequate levels had been maintained. We rated the internal circuits of the device at the 7 year mark, comparing the insides of both the used and unused new Synflex tubing, silicone blades, Teflon tubing, silicone rubber tubing, and stainless steel parts. No bacteria or contamination (such as endotoxins) was detected, and no degradation or damage were observed. Even after the auto-hot water disinfection system was installed, no internal tubing degradation due to hot water or mechanical issues have occurred, and the system's dialysis fluid purification levels have been maintained.

Routine online assessment of dialysis dose: Ionic dialysance or UV-absorbance monitoring?

For three-weekly hemodialysis, a single-pool Kt/V target of at least 1.4 together with a minimal dialysis dose Kt at 45 L for men and 40 L for women per each session is currently recommended. Fully automatic online calculation of Kt and Kt/V from conductivity or UV-absorbance measurements in the dialysate is standardly implemented on some hemodialysis monitors and makes it possible to estimate the dialysis dose without the need for blood or dialysate samples. Monitoring the UV-absorbance of the spent dialysate is the most direct method for estimating Kt/V as it does not require an estimate of V. Calculation of ionic dialysance from conductivity measurements is the most direct method for estimating Kt and BSA-scaled dialysis dose. Both ionic dialysance monitoring and UV-absorbance monitoring may help detect a change in urea clearance occurring during the session, but this change must be interpreted differently depending on the monitoring being considered. An abrupt decrease in urea clearance results in a decrease in ionic dialysance but, paradoxically, a sudden increase in estimated urea clearance provided by dialysate UV-absorbance monitoring. Healthcare teams who monitor both ionic dialysance and UV-absorbance in their hemodialysis units must be clearly informed of this difficulty.

Health Technology Assessment of a new water quality monitoring technology: Impact of automation, digitalization and remoteness in dialysis units.

BACKGROUND: Water quality monitoring at the dialysis units (DU) is essential to ensure an appropriate dialysis fluid quality and guarantee an optimal and safe dialysis treatment to patients. This paper aims to evaluate the effectiveness, economic and organizational impact of automation, digitalization and remote water quality monitoring, through a New Water Technology (NWT) at a hospital DU to produce dialysis water, compared to a Conventional Water Technology (CWT). METHODS: A before-and-after study was carried out at the Hospital Clínic Barcelona. Data on CWT was collected during 1-year (control) and 7-month for the NWT (case). Data on water quality, resource use and unit cost were retrospective and prospectively collected. A comparative effectiveness analysis on the compliance rate of quality water parameters with the international guidelines between the NWT and the CWT was conducted. This was followed by a cost-minimization analysis and an organizational impact from the hospital perspective. An extensive deterministic sensitivity analysis was also performed. RESULTS: The NWT compared to the CWT showed no differences on effectiveness measured as the compliance rate on international requirements on water quality (100% vs. 100%), but the NWT yielded savings of 3,599 EUR/year compared to the CWT. The NWT offered more data accuracy (daily measures: 6 vs. 1 and missing data: 0 vs. 20 days/year), optimization of the DU employees' workload (attendance to DU: 4 vs. 19 days/month) and workflow, through the remote and continuous monitoring, reliability of data and process regarding audits for quality control. CONCLUSIONS: While the compliance of international recommendations on continuous monitoring was performed with the CWT, the NWT was efficient compared to the CWT, mainly due to the travel time needed by the technical operator to attend the DU. These results were scalable to other economic contexts. Nonetheless, they should be taken with caution either when the NWT equipment/maintenance cost are largely increased, or the workforce involvement is diminished.

Quantitative assessment of sodium mass removal using ionic dialysance and sodium gradient as a proxy tool: Comparison of high-flux hemodialysis versus online hemodiafiltration.

Restoration and maintenance of sodium are still a matter of concern and remains of critical importance to improve the outcomes in homeostasis of stage 5 chronic kidney disease patients on dialysis. Sodium mass balance and fluid volume control rely on the "dry weight" probing approach consisting mainly of adjusting the ultrafiltration volume and diet restrictions to patient needs. An additional component of sodium and fluid management relies on adjusting the dialysate-plasma sodium concentration gradient. Hypotonicity of ultrafiltrate in online hemodiafiltration (ol-HDF) might represent an additional risk factor in regard to sodium mass balance. A continuous blood-side approach for quantifying sodium mass balance in hemodialysis and ol-HDF using an online ionic dialysance sensor device ("Flux" method) embedded on hemodialysis machine was explored and compared to conventional cross-sectional "Inventory" methods using anthropometric measurement (Watson), multifrequency bioimpedance analysis (MF-BIA), or online clearance monitoring (OCM) to assess the total body water. An additional dialysate-side approach, consisting of the estimation of inlet/outlet sodium mass balance in the dialysate circuit was also performed. Ten stable hemodialysis patients were included in an "ABAB"-designed study comparing high-flux hemodialysis (hf-HD) and ol-HDF. Results are expressed using a patient-centered sign convention as follows: accumulation into the patient leads to a positive balance while recovery in the external environment (dialysate, machine) leads to a negative balance. In the blood-side approach, a slight difference in sodium mass transfer was observed between models with hf-HD (-222.6 [-585.1-61.3], -256.4 [-607.8-43.7], -258.9 [-609.8-41.3], and -258.5 [-607.8-43.5] mmol/session with Flux and Inventory models using VWatson , VMF-BIA , and VOCM values for the volumes of total body water, respectively; global P value < .0001) and ol-HDF modalities (-235.3 [-707.4-128.3], -264.9 [-595.5-50.8], -267.4 [-598.1-44.1], and -266.0 [-595.6-55.6] mmol/session with Flux and Inventory models using VWatson , VMF-BIA , and VOCM values for the volumes of total body water, respectively; global P value < .0001). Cumulative net ionic mass balance on a weekly basis remained virtually similar in hf-HD and ol-HDF using Flux method (P = n.s.). Finally, the comparative quantification of sodium mass balance using blood-side (Ionic Flux) and dialysate-side approaches reported clinically acceptable (a) agreement (with limits of agreement with 95% confidence intervals (CI): -166.2 to 207.2) and (b) correlation (Spearman's rho = 0.806; P < .0001). We validated a new method to quantify sodium mass balance based on ionic mass balance in dialysis patients using embedded ionic dialysance sensor combined with dialysate/plasma sodium concentrations. This method is accurate enough to support caregivers in managing sodium mass balance in dialysis patients. It offers a bridging solution to automated sodium proprietary balancing module of hemodialysis machine in the future.

Which Method Should Be Used to Assess Protein Intake in Peritoneal Dialysis Patients? Assessment of Agreement Between Protein Equivalent of Total Nitrogen Appearance and 24-Hour Dietary Recall.

OBJECTIVES: After dialysis initiation, a high protein diet is recommended due to significant nutrient losses through dialysate and increased risk of protein energy wasting. In peritoneal dialysis (PD) patients, protein intake can be assessed through different methods that have some advantages and limitations, which affect its use on routine care. The aim of this study is to evaluate the agreement between 2 different methods (24-hour dietary recall and PNA-protein equivalent of total nitrogen appearance) on estimating protein intake in PD patients. DESIGN AND METHODS: Patients on PD for at least 3 months, aged 18 years old or more, were enrolled. To estimate protein intake, 24-hour dietary recall and PNA was used. PNA was calculated from 24-hour urine on the same day of the 24-hour dietary recall. RESULTS: Fifty individuals on PD were included, mean age 55.7 ± 16.2 years, and body mass index 26.0 ± 4.5 kg/m2. The average energy consumption was 1788.79 ± 504.40 kcal/day, which corresponds to 26.81 ± 9.11 kcal/kg current body weight (BW)/day and 29.82 ± 8.39 kcal/kg ideal body weight (IBW)/day. The median of total daily and normalized protein intake estimated using dietary recall was 61.43 (45.28-87.40) g/day, 0.90 (0.58-1.22) g/kg current BW/day, and 1.04 (0.77-1.32) g/kg IBW/day, respectively. Daily protein intake estimated by PNA was 55.75 (48.27-67.74) g/day, protein intake normalized by current BW was 0.81 (0.72-0.99) g/kg and 0.92 (0.83-1.06) g/kg IBW/day. Bland-Altman analysis indicates no systematic bias for the assessment of total protein intake and normalized protein intake for current and ideal BW. Significant proportionality bias was observed for both evaluations, showing there is a dispersion of the values. CONCLUSIONS: Despite the absence of systematic bias in the Bland-Altman analysis, there is no agreement in the assessment of protein intake by dietary recall and PNA, due to the existence of proportionality bias. Thus, values can be influenced biased by the magnitude of the measures.

Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic.

With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic.

Urgent Peritoneal Dialysis in Patients With COVID-19 and Acute Kidney Injury: A Single-Center Experience in a Time of Crisis in the United States.

At Montefiore Medical Center in The Bronx, NY, the first case of coronavirus disease 2019 (COVID-19) was admitted on March 11, 2020. At the height of the pandemic, there were 855 patients with COVID-19 admitted on April 13, 2020. Due to high demand for dialysis and shortages of staff and supplies, we started an urgent peritoneal dialysis (PD) program. From April 1 to April 22, a total of 30 patients were started on PD. Of those 30 patients, 14 died during their hospitalization, 8 were discharged, and 8 were still hospitalized as of May 14, 2020. Although the PD program was successful in its ability to provide much-needed kidney replacement therapy when hemodialysis was not available, challenges to delivering adequate PD dosage included difficulties providing nurse training and availability of supplies. Providing adequate clearance and ultrafiltration for patients in intensive care units was especially difficult due to the high prevalence of a hypercatabolic state, volume overload, and prone positioning. PD was more easily performed in non-critically ill patients outside the intensive care unit. Despite these challenges, we demonstrate that urgent PD is a feasible alternative to hemodialysis in situations with critical resource shortages.

Bioimpedance spectroscopy for fluid status assessment in patients with decompensated liver cirrhosis: Implications for peritoneal dialysis.

Bioimpedance spectroscopy (BIS) is routinely used in peritoneal dialysis patients and might aid fluid status assessment in patients with liver cirrhosis, but the effect of ascites volume removal on BIS-readings is unknown. Here we determined changes in BIS-derived parameters and clinical signs of fluid overload from before to after abdominal paracentesis. Per our pre-specified sample size calculation, we studied 31 cirrhotic patients, analyzing demographics, labs and clinical parameters along with BIS results. Mean volume of the abdominal paracentesis was 7.8 ± 2.6 L. From pre-to post-paracentesis, extracellular volume (ECV) decreased (20.2 ± 5.2 L to 19.0 ± 4.8 L), total body volume decreased (39.8 ± 9.8 L to 37.8 ± 8.5 L) and adipose tissue mass decreased (38.4 ± 16.0 kg to 29.9 ± 12.9 kg; all p < 0.002). Correlation of BIS-derived parameters from pre to post-paracentesis ranged from R² = 0.26 for body cell mass to R² = 0.99 for ECV. Edema did not correlate with BIS-derived fluid overload (FO ≥ 15% ECV), which occurred in 16 patients (51.6%). In conclusion, BIS-derived information on fluid status did not coincide with clinical judgement. The changes in adipose tissue mass support the BIS-model assumption that fluid in the peritoneal cavity is not detectable, suggesting that ascites (or peritoneal dialysis fluid) mass should be subtracted from adipose tissue if BIS is used in patients with a full peritoneal cavity.

Feasibility of osmotic dilution for recycling spent dialysate: Process performance, scaling, and economic evaluation.

Hemodialysis is one of the therapies for patients with kidney failure. Hemodialysis requires large amounts of pure water, and is one of the most water-hungry medical procedures, and thus represents a clear opportunity where improvements should be made concerning the consumption and wastage of water. In this paper, we explored the potential of forward osmosis (FO) membrane for recycling the spent dialysate using the dialysis concentrate as the draw solution. Partially diluted dialysis concentrate could be further diluted with pure water to form dialysate for further dialysis process. Using commercial cellulose triacetate (CTA) FO membranes, the water recovery of approximately 64% was achieved and the final volume of the partially diluted dialysis concentrate was about four times the initial volume. Flux decline of the FO process was observed, mainly due to concentration of synthetic spent dialysate and dilution of dialysis concentrate, while membrane scaling had little impact on the flux decline. The urea rejection was found to be relatively low owing to the small size and electroneutral nature of the urea molecule. Obvious membrane scaling was observed after three FO cycles. The energy dispersive spectroscopy analysis of the scaling layer indicated that the scalants were phosphates and carbonates. The scaling was removed via osmotic backwash and almost completely recovery of FO flux was obtained. Economic analysis showed that the centralized treatment of spent dialysate in a dialysis center using the proposed osmotic dilution process could greatly save water resources and cost. Improving the urea rejection of FO membrane was identified as an important research focus for future research on the potential application of FO technology for recycling the spent dialysate in hemodialysis.

Contemporary trends and outcomes of mitral valve surgery for infective endocarditis.

BACKGROUND: Contemporary data on mitral valve (MV) surgery in patients with infective endocarditis (IE) are limited. METHODS: The National Inpatient Sample was queried to identify patients with IE who underwent MV surgery between 2003 and 2016. We assessed (a) temporal trends in the incidence of MV surgery for IE, (b) morbidity, mortality, and cost of MV repair vs replacement, and (c) predictors of in-hospital mortality. RESULTS: The proportion of MV operations involving patients with IE increased from 5.4% in 2003 to 7.3%, and the proportion of MV repair among those undergoing surgery for IE increased from 15.2% to 25.0% (Ptrend < .001). In-hospital mortality was higher in the replacement group (11.3% vs 8.1%; P < .001), and this excess mortality persisted after propensity score matching (11.2% vs 8.1%; P < .001), and in sensitivity analyses excluding concomitant surgery (unadjusted 11.3% vs 4.8%; adjusted 8.5% vs 4.5%; P < .001), and stratifying patients by the time of operation (within 7 days, 11.3% vs 6.8%; P < .001 and >7 days, 11.9% vs 9.1%; P = .012). In the propensity-matched cohorts, shock and need for tracheostomy were more frequent in the replacement group, but rates of stroke, pacemaker implantation, new dialysis, and blood transfusion were similar. Mitral valve repair was, however, associated with shorter hospitalizations, more home discharges, and less cost. In a multivariate regression analysis, age above 70 and chronic dialysis were the strongest predictors of in-hospital mortality. CONCLUSION: Mitral valve repair in IE patients is associated with lower in-hospital mortality, resource utilization, and cost compared with MV replacement.

In vitro assessment of mixed matrix hemodialysis membrane for achieving endotoxin-free dialysate combined with high removal of uremic toxins from human plasma.

For a single hemodialysis session nearly 500 L of water are consumed for obtaining pyrogen-free dialysis fluid. However, many efforts are required to avoid biofilm formation in the system and risk of contamination can persist. Water scarcity and inadequate water purification facilities worsen contamination risk in developing countries. Here, we investigated the application of an activated carbon (AC)/polyethersulfone/polyvinylpyrrolidone mixed matrix membrane (MMM) for achieving for the first time endotoxin-free dialysate and high removal of uremic toxins from human plasma with a single membrane. The MMM, thanks to sorbent AC, can remove approximately 10 times more endotoxins from dialysis fluid compared to commercial fibers. Pyrogens transport through the MMM was investigated analyzing inflammation in THP-1 monocytes incubated with samples from the dialysis circuit, revealing safety-barrier properties of the MMM. Importantly, endotoxins from dialysate and protein-bound toxins from human plasma can be removed simultaneously without compromising AC adsorption capacity. We estimated that only 0.15 m2 of MMM is needed to totally remove the daily production of the protein-bound toxins indoxyl sulfate and hippuric acid and to completely remove endotoxins in a wearable artificial kidney (WAK) device. Our results could open up new possibilities for dialysis therapy with low water consumption including WAK and where purity and scarcity of water are limiting factors for hemodialysis treatment. STATEMENT OF SIGNIFICANCE: Hemodialysis is a life-sustaining extracorporeal treatment for renal disease, however the production of pyrogen-free dialysate is very costly and water demanding. Biofilm formation in the system worsens bacteria contamination risk. Pyrogens could be transferred into the patients' blood and trigger inflammation. Here, we show for the first time that a mixed matrix membrane composed of polyethersulfone/polyvinylpyrrolidone and activated carbon can achieve simultaneous complete removal of endotoxins from dialysate and high removal of uremic toxins from human plasma without compromising activated carbon adsorption capacity. The mixed matrix membrane could find future applications for simultaneous blood purification and dialysate depyrogenation thus lowering water consumption as for wearable artificial kidney devices and where purity and scarcity of water hamper hemodialysis treatment.

Hypoalbuminemia: a price worth paying for improved dialytic removal of middle-molecular-weight uremic toxins?

Hemodiafiltration (HDF) increases the removal of middle-molecular-weight uremic toxins and may improve outcomes in patients with end-stage kidney disease (ESKD), but it requires complex equipment and comes with risks associated with infusion of large volumes of substitution solution. New high-flux hemodialysis membranes with improved diffusive permeability profiles do not have these limitations and offer an attractive alternative to HDF. However, both strategies are associated with increased albumin loss into the dialysate, raising concerns about the potential for decreased serum albumin concentrations that have been associated with poor outcomes in ESKD. Many factors can contribute to hypoalbuminemia in ESKD, including protein energy wasting, inflammation, volume expansion, renal loss and loss into the dialysate; of these factors, loss into the dialysate is not necessarily the most important. Furthermore, recent studies suggest that mild hypoalbuminemia per se is not an independent predictor of increased mortality in dialysis patients, but in combination with inflammation it is a poor prognostic sign. Thus, whether hypoalbuminemia predisposes to increased morbidity and mortality may depend on the presence or absence of inflammation. In this review we summarize recent findings on the role of dialysate losses in hypoalbuminemia and the importance of concomitant inflammation on outcomes in patients with ESKD. Based on these findings, we discuss whether hypoalbuminemia may be a price worth paying for increased dialytic removal of middle-molecular-weight uremic toxins.

Assessment and Management of Hypertension among Patients on Peritoneal Dialysis.

Approximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.